Poster Session 60 Allergy and the nose

139 Pages·2013·1.26 MB·English

Poster Session 57
Effector cells in inflammation
1367 was no difference in mast cell sensitivity 1369
betweenatopicandnon-atopicsubjects. Immunodeficiency,hypopituitarismand
Roleofthediseasestatusofthedonor Conclusion: Cultured mast cells from mastocytosis:apuzzlingassociation
onsensitivityofculturedmastcells asthma patients and controls respond with
DiCapua,L;Palladino,A;Petraroli,A;Marone,GC;
similar sensitivity to allergen activation.
Krohn,IK1;Sverrild,A2;Lund,G3;Dahl,R4;Backer,V2; Spadaro,G;Genovese,A
Hoffmann,HJ1 Degranulation of cultured mast cells DepartmentofTranslationalMedicine,Universityof
1DepartmentofPulmonaryMedicine,AarhusUniversity appears to depend more on culture condi- Naples‘FedericoII’,Naples,Italy
Hospital,AarhusC,Denmark;2Departmentof tions (IL-4, IgE) than on donor status
RespiratoryMedicineL,BispebergUniversityHospital, Background: Authors emphasize the role
CopenhagenNW,Denmark;3ALK-Abello(cid:1),Hørsholm, (atopyorasthma).
Denmark;4ClinicalInstitute,DepartmentofHealth, of hormones for T and B cell to generate
AarhusUniversity,Aarhus,Denmark humoral or cell mediated immune
responses. Compelling evidence confirm
Background: Binding of IgE to FceRI 1368 that B lineage deficiency, in the absence of
increases the expression of FceRI on mast LeukotrieneE4regulatesgeneexpression thyroid hormone, is due to the decreased
cells and basophil granulocytes. Distinct inhumanmastcells survival or lower rate of proliferation of
properties (affinity of IgE for allergen, clo- committedBcellprecursors.
nality of allergen, fraction of specific IgE Foster,HR;Fuerst,E;Lee,TH;Woszczek,G Method: A 39-year-old white man pre-
KingsCollegeLondon,Asthma,AllergyandRespiratory
of total IgE) of the IgE repertoire deter- Science,London,UnitedKingdom sented to our Department for not pruritic,
mine basophil degranulation on exposure Darier’s sign positive, red-brown macules
to allergen. We investigated whether dis- Background: Leukotriene E4 (LTE4), the gradually appeared and distributed over
ease status (atopy or asthma) of the donor most stable of the cysteinyl leukotrienes trunk, upper arms and neck. Medical his-
influences the sensitivity of mast cells cul- (cysLT), binds poorly to classical type 1 tory included a GH-deficiency treated with
turedunderidenticalconditions. (CysLT1) and 2 (CysLT2) cysLT receptors replacement therapy from 12 to 16 year
Method: This study included 12 patients although in asthmatic individuals it may old. No history of recurrent infections,
with an objectively confirmed asthma diag- potently induce bronchial constriction, air- familiar immunodeficiency or thyroid dis-
nosis according to GINA-guidelines and way hyperresponsiveness and inflammatory ease. Physical examination revealed a
eight healthy subjects. Allergic sensitisation cell influx to the lung. In recombinant height of 168 cm and weight of 83 kg. The
was defined as a positive skin prick test models, LTD4 potently activates calcium skin was dry, hair and eyebrows were thin-
(>3 mm) response to at least 1 of 10 aller- mobilisationwhileLTE4inducesveryweak ning. Examination of other districts was
gensinastandardpanel.Tensubjectswere responses. In contrast, in a human mast normal.
atopic,and10werenon-atopic.Weinvesti- cell line, LAD2, LTE4 induced calcium Results: Hormones dosage showed hypo-
gated the sensitivity for IgE-mediated acti- with similar potency as LTD4, with EC50 thyroidism (FT4 0.83 lg/dl, TSH
vation of peripheral blood derived mast 9.3 nM and 4.9 nM for LTE4 and LTD4, 6.660 lU/ml) while antithyroperoxidase
cells. During the last 2 weeks of culture, respectively. Our aim was to analyse and antithyreoglobulin antibodies were
mast cells were sensitised with IL-4 and responsiveness of human mast cells to negative. Data confirmed low levels of GH
80 kU/l recombinant human IgE contain- cysLTs. (IGF-1 <25 ng/ml; GH <0.05 ng/ml) show-
ing two IgE clones (7% + 7%) specific for Method and results: LTE4 was the most ing also testosterone deficiency. Antipitu-
recombinantmiteallergenDerp2. potent activator of gene expression in itary antibodies were negative. Moreover
Results: Wefoundnosignificantdifference LAD2 cells when measured using Affyme- we revealed humoral immunodeficiency
in the number of mast cells cultured from trix microarrays, regulating the expression (IgA 0.441 g/l, IgM 0.317 g/l, IgG 8.940 g/
asthma patients compared to controls. of more than 70 genes, including immedi- l) with normal values of T and B cell sub-
After activation, the maximal CD63 Med- ate early genes, transcription factors, cyto- populations. Brain MRI evidenced Chiari
ian Fluorescence Intensity was 20 kines and membrane receptors. This has type I malformation and reduced volume
456 (cid:1) 1640 [standard error (SE)] for been confirmed for a selection of genes at of the anterior pituitary gland. Posterior
asthma patients and 22 275 (cid:1) 1971 (SE) themRNAandproteinlevel.Althoughthe pituitary gland and hypothalamus were
for controls [not significant (ns)] and the pattern of responses to cysLTs did not normal. Bone density scan (DEXA) evi-
percentage CD63+ mast cells was 54.4% resembleclassical CysLT1 orCysLT2activ- denced a severe osteoporosis (T-score
forasthmapatientsand48.4%forcontrols ity, both intracellular calcium signalling (cid:3)3.1; Z-score (cid:3)3.0). No evidence of focal
(ns). The sensitivity, EC50Der p2, (effective and gene expression were significantly lesions by X-ray of major bones. Echocar-
allergenconcentrationinducing50%ofthe inhibited by CysLT1 inhibitor montelukast diogram exhibited normal volume of heart
maximalresponse)basedonthepercentage and not affected by CysLT2 inhibitor cavities. Histology of skin biopsy con-
CD63+ mast cells of all mast cell lines cul- HAMI3379. firmed mast cell accumulation in a perivas-
tured from patients with asthma and con- Conclusion: Ourdatasuggestthatleukotri- culardistributionwithinderma.
trols was comparable (0.332 ng/ml (cid:1) 1.235 eneE4isapotentactivatorofhumanmast Conclusion: Wefirstdescribetheassociation
(SE) for asthma patients and 0.232 ng/ cells acting potentially through CysLT1 or of hypopituitarism, immunodeficiency and
ml (cid:1) 1.211 (SE) for controls (ns). There anunidentifiedreceptor. mastocytosis, a rare disorder characterised
498 ©2013TheAuthors
Allergy©2013JohnWiley&SonsA/S.PublishedbyJohnWiley&SonsLtd,68(Suppl.97),498–636
PosterSession57–Effectorcellsininflammation
bymastcellproliferationandaccumulation tionbycolleaguesandcametothehospital symptoms was present in 41 (85.4%), gas-
within various organs, most commonly the in coma. EKG showed diffuse ST depres- trointestinal in33(68.8%), musculoskeletal
skin. This association supports in vivo the sion, echocardiography was normal. Tryp- in 17 (35.4%) and neuropsychiatric in 15
functional link between the endocrine and tase values were significantly higher (31.2%) patients. Seventeen (35.4%) had
immune systems as shown in many reports (200 lg/ml)andkeptelevatedafter10 days experienced at least one anaphylactic epi-
where the development and function of the (18.6 lg/ml). Fine needle aspiration and sode. Fourteen (29.2%) had osteoporosis
immune system are strightly related to hor- bone marrow biopsy showed mast-cell and additional 18 (37.5%) had osteopenia.
monal levels. In this patient hormonal defi- hyperplasia with mast-cell paratrabecular No significant differences in KIT D816V
ciency may have been the cause of aggregates CD117 and CD68 positive and mutationlevelweredetectedwhencompar-
immunodeficiency.Westresstheimportance rare CD2 positive cells. PCR-RFLP did ing patients with none/mild symptoms and
ofimmunologicalscreeninginpatientswith not show D816V mutation of the c-kit patients with moderate/severe symptoms,
hormonal deficiency, even if asymptomatic, gene. patients with and without anaphylaxis or
since, in some cases, replacement hormonal Conclusions: A relatively uncommon clini- patients with osteoporosis/osteopenia and
therapycancorrectimmunodeficiency. cal feature like a cardiac arrest may under- normal BMD. Even though some of the
line a rare disease like systemic included patients exhibited high mutation
mastocytosis, so that diagnosis should be levels,nonehadprogressionintoaggressive
considered in every case of cardiac arrest formsofSMintheobservationperiod.
1370 not otherwise explainable. Serum level of Conclusion: FractionofKITD816Vmuta-
Systemicmastocytosisintheemergency tryptase demonstrates a high specificity in tion positive cells is a new parameter gen-
department confirmingthediagnosis. erally applicable in SM. In the present
studywedidnotdetectanysignificant cor-
Olivieri,E;Montagni,M;Bonzano,L;Ticinesi,A;
Meschi,T;Ridolo,E relation between the severity of clinical
ClinicalandExperimentalMedicine,Universityof manifestationsandthelevelofKITD816V
Parma,Parma,Italy
1371 mutated cells. Whether this reflects the
KITD816Vmutationburdendoesnot KIT D816V mutation being carried by
Introduction: Systemic mastocytosis is a
correlatetomediatorrelatedsymptoms, cells of non-MC lineage or by non-mature
rather uncommon disease characterised by
anaphylaxisorosteoporosisinindolent MC-progenitorsispresentlynotclear.
mast-cell proliferation and massive release
systemicmastocytosis
of vasoactive mediators such as histamine.
Its clinical features generally include ery- Broesby-Olsen,S1,2;Kristensen,T3;Vestergaard,H2,4;
Brixen,K2,5;Møller,MB2,3;Bindslev-Jensen,C1,2;Mast-
thema, urticaria, hypotension and epato-
ocytosisCentreOdenseUniversityHospital(MastOUH) 1372
splenomegaly. Less common clinical mani- 1DepartmentofDermatologyandAllergyCentre,
Idiopathicanaphylaxisasapresenting
festation are possible. We report two cases OdenseUniversityHospital,OdenseC,Denmark;
2InstituteofClinicalResearch,UniversityofSouthern symptomofclonalmastcelldisorders
in which a cardiac arrest was the first
Denmark,Odense,Denmark;3DepartmentofPathology,
appearanceofthedisease. OdenseUniversityHospital,Odense,Denmark; Gulen,T1,2;Ha€gglund,H2,3;Dahle(cid:1)n,B1,2;Nilsson,G2,4
Case 1: A 72-year-old male previously in 4DepartmentofHematology,OdenseUniversity 1DepartmentofRespiratoryDiseasesandAllergy,
good health, suddenly complained of epi- EHnodspoictrailn,oOlodgeyn,sOe,dDeennsemUarnki;v5eDrseiptyarHtmosepnittaol,fOdense, KSawreodlienns;ka2KUanroivlienrsskitayInHsotsitpuitteatlaHnudddKianrgoeli,nSstkoackholm,
gastric pain after dinner, rapidly followed Denmark UniversityHospital,MastocytosisCenterKarolinska,
by nausea, vomiting and loss of conscious- Stockholm,Sweden;3DepartmentofHematology,
KarolinskaUniversityHospitalHuddinge,Stockholm,
ness. When emergency medical team Background: Patients with indolent sys- Sweden;4DepartmentofMedicine,KarolinskaInstitutet,
reached, he appeared unconscious, with temic mastocytosis (ISM) suffer from CLImmunologyandAllergyResearchUnit,Stockholm,
respiratory activity but pulseless. EKG mediator related symptoms, anaphylaxis Sweden
showed no electrical activity. A laryngeal and osteoporosis. A new method for KIT
Background: Idiopathicanaphylaxis(IA)is
tube was positioned and epinephrine 2 mg D816V mutation detection allows determi-
a diagnosis of exclusion and remains to be
was administered, obtaining a reprise of nation of the level of mutation positive
a challenge for allergists. Multiple theories
cardiac activity. The EKG showed a mild cells.
on the pathogenesis of IA have been pro-
ST elevation in inferior leads and signs of Objective: To investigate whether the
posed, although none of them can explain
anterior subendocardic ischemia, recovered severity of clinical manifestations in adult
the underlying mechanisms. Clonal mast
in the following EKGs. Echocardiography, patients with ISM correlates to the level of
cell disorders (CMD) and its substantial
coronaryangiographyandserumtroponins KIT D816V positive cells in peripheral
overlapintheclinicalmanifestationsofidi-
werenormal.Alaboratorytestfortryptase blood(PB)orbonemarrow(BM)aspirate.
opathic anaphylaxis have led to the search
was then performed and showed markedly Methods: We included 48 adult ISM-
elevated values (75 lg/ml). Bone-marrow patients (28 female/20 male) from our cen- foranassociationbetweentheseraredisor-
ders. Currently, two forms of CMD have
biopsy and fine-needle aspiration showed a tre in whom the KIT D816V mutation
been characterised: systemic mastocytosis
pattern of severe mast-cell hyperplasia, level in both BM aspirate and PB was
(SM) and monoclonal mast cell activation
with atypical inter- and paratrabecular available. For each patient the severity of
syndrome (MMAS). In this study, we
mast-cell aggregates CD117 and CD25 mediator related symptoms (skin, gastroin-
sought to determine the prevalence of
positive and CD2 and CD34 negative. testinal, musculoskeletal and neuropsychi-
CMDamongIApatients,andtoexploreif
PCR-RFLP highlighted D816V mutation atric) was graded and episodes of
pathogenesis of IA could be explained by
of the c-kit gene. We therefore made the anaphylaxis were evaluated by interview
unrecognisedCMD.
diagnosisofseveresystemicmastocytosis. andmedicalrecordfiles.Bonemineralden-
Method: We identified patients (≥18 year)
Case2: A57-year-oldmale,withnoprevi- sity (BMD) was determined by dual-energy
who were referred to the Allergy clinic
ous history of allergic or cardiac diseases, x-rayabsorptiometry(DXA).
betweenJanuary2006 andDec2012dueto
developed general malaise, flushing and Results: Median fraction (range) of KIT
loss of consciousness while was at work. D816V positivecellswas0.6(0.01–90)%in recurrent or unexplained anaphylaxis. All
He was given cardiopulmonary resuscita- BM and 0.3 (0.003–49)% in PB. Skin patients initially underwent a complete
allergy work-up; thereby the diagnosis of
©2013TheAuthors 499
Allergy©2013JohnWiley&SonsA/S.PublishedbyJohnWiley&SonsLtd,68(Suppl.97),498–636
PosterSession57–Effectorcellsininflammation
IA was confirmed after exclusion of possi- with corticosteroid plus cyclophosphamide Eighteen caseshadmoderatehypereosin-
ble elicitors. Baseline tryptase (sBT) levels pulses, and 17 patients were treated with ophilia (3000<, ≤5000/lL) due to drug (7),
were measured. Twenty-seven patients, 14 corticosteroid alone. Ten patients were lost bronchial asthma (2), myeloproliferative
malesand13females,whoeitherhadmini- to follow-up and three patients expired. disease (2), milk allergy (1), Kimura′s dis-
mumofthreeanaphylacticreactionsorele- One patient died of heart failure due to ease (1), urticarial (1), PIE syndrome (1),
vated sBT levels (>11.4 ng/ml) regardless uncontrolled vasculitis, and two died of urethralcancer(1),andunknowncause(2).
of the number of anaphylactic episodes pancreatic cancer and unknown etiology. Thirty three patients were with milder
wererecruitedandenrolledinthisprospec- Twenty four patients showed sustained hypereosinophilia (1500<, ≤3000/lL) asso-
tive study. None of the patients had signs remission, of which seven patients could ciated with drug (9), malignancy (5),
of urticaria pigmentosa. All 27 patients discontinuethemedication,and17patients Gleich syndrome (2), egg allergy (2), bron-
further underwent a bone marrow biopsy werewellcontrolled with low-dose(<5 mg/ chial asthma (1), atopic dermatitis (1),
and aspirate to investigate clonal markers day)prednisolone. myeloproliferative disease (1) and unidenti-
of CMD and underlying mast cell hyper- Conclusion: CSS was highly variable in fied cause (12). Some adverse drug effects
reactivity using current WHO-criteria. We its presentation, and the prognosis was and Gleich syndrome were not diagnosed
evaluated characteristics of the bone mar- relatively good if the patients get proper by the doctors in charge, but by revising
row mast cells by pathology, flow cytome- treatment. process.
tryanddetectionofKITD816Vmutation. Interestingly, 14 cases with unknown eti-
Results: Thirteen (48%) out of 27 investi- ology include four cases with artificial ves-
gated patients (10 males and 3 females) sels or stents and three cases with renal
werediagnosedwithCMD;8withindolent 1375 failure. And four of the six patients with
systemic mastocytosis (ISM) and 5 with Etiologyofhypereosinophilia cancer were urinary tract origin. No para-
MMAS. All ISM patients had a sBT levels Katada,Y1;Harada,Y1;Yura,A1;Kagawa,K2;Kishioka, siticinfectionwasnoted.
>11.4 ng/ml (in six patients >20 ng/ml), A3;Yamaguchi,N4;Inoue,N5;Hashizume,T6; Conclusion: Adverse drug effect is the
whereas sBT was elevated only in two Hashimoto,J7;Saeki,Y1;Tanaka,T8 most frequent origin of hypereosinophilia
1NHOOsaka-MinamiMedicalCenter,Allergyand
MMAS patients (15 and 23 ng/ml). Four regardless of its severity. Antibiotics, pro-
ClinicalImmunology,Kawachinagano,Japan;2NHO
of the eight patients with ISM had bone Osaka-MinamiMedicalCenter,MedicalInformation, ton pump inhibitors, and anti-epileptics
marrow mast cell aggregates. Among 14 Kawachinagano,Japan;3NHOOsaka-MinamiMedical account for two-thirds of drug-induced hy-
Center,Dermatology,Kawachinagano,Japan;4NHO
non-clonal IA patients, only one had ele- pereosinophilia. As it is difficult to make
Osaka-MinamiMedicalCenter,Respiratology,
vated (17 ng/ml) level of sBT. There was a Kawachinagano,Japan;5NHOOsaka-MinamiMedical simultaneous adequate evaluation of hy-
clear male predominance in patients with Center,Pediatrics,Kawachinagano,Japan;6NHO pereosinophilia in some cases, especially in
CMD(77%). Osaka-MinamiMedicalCenter,PediatricsandClinical milder cases, revision, considering entire
Laboratory,Kawachinagano,Japan;7NHOOsaka-
Conclusion: In this study, mechanism of MinamiMedicalCenter,ClinicalImmunology, clinical course, is a useful way to seek the
IA could be explained by a hyper-reactive Kawachinagano,Japan;8OsakaUniversityGraduate etiologies.
mast cell phenotype in 48% of the IA SchoolofMedicine,ClinicalApplicationofBiologics,
Suita,Japan
patients. Thus, our study suggests that clo-
nal mast cell disorders are a substantial Background: The most frequent cause of
differential diagnosis of IA, particularly in eosinophilia worldwide is helminth infec- 1377
malepatientswithelevatedsBT. tions, while that in industrialized nations is Montelukastreducesperipheralblood
eosinophiliainatopicchildren
atopic diseases, which are often accompa-
niedwithmildeosinophilia (<1500/lL).On Ehlayel,MS1;AbuLaban,M2;Ashour,R3
the other hand, eosinophilia (>1500/lL) is 1DepartmentofPediatrics,HamadMedCorp,Weill
1374 CornellMedicalCollege-Qatar,SectionofPedAllergy-
Theclinicalfeaturesandlong-term defined as hypereosinophilia, indicating Immunology,Doha,Qatar;2DepartmentofPediatrics,
existenceofsomespecialcauses. HamadMedCorp,SectionofPediatricsHematology-
prognosisofChurg-Strausssyndrome Method: We explored all patients with hy- Oncology,Doha,Qatar;3DepartmentofPediatrics,
Lee,B-J1;Lee,J-Y2;Oh,M-J3;Choi,D-C1 pereosinophilia (>1500/lL) who visited our HamadMedCorp,Doha,Qatar
1SamsungMedicalCenter,SungkyunkwanUniversity medicalcenterin2012andreviewedtocat-
SchoolofMedicine,InternalMedicine,Seoul,Korea; Background and objectives: Theantiinflam-
2SamsungMedicalCenter,CenterforHealth egorise their etiologies according to the matory properties of montelukast were
Promotion,Seoul,Korea;3BundangJaesengHospital, severityofeosinophilia.Ourmedicalcenter reported in reducing tissue eosinophilia in
InternalMedicine,Seongnam,Korea located in an urban area in Japan has
asthma,nasalpolyps,duodenaleosinophilia,
about 1000 outpatients and 500 inpatients
Background: Churg-Strausssyndrome(CSS) eosinophilic esophagitis and gastroenteritis.
aday.
is a rare disease characterised by asthma, Thisisthefirstreporttoobservetheeffectof
Results: There were 64 patients with hy-
eosinophilia,andsystemicvasculitis. montelukast on reducing peripheral eosino-
pereosinophilia. The overall most frequent
Method: We retrospectively analyzed clini- philia,particularlyinchildren.
cal manifestations and long-term outcomes causewasadversedrugeffect(22).Presum- Case 1: A 10½ year boy, relocated to
able responsible drugs include antibiotics
of 53 patients who diagnosed as CSS at Doha, had been diagnosed to have asymp-
(6: ABPC, LVFX, etc.), proton-pump
Samsung Medical Center from 1995 to tomatic, unexplained, persistent blood
inhibitors (5: omeprazole, lansoplazole,
2011. Subjects included 27 men and 26 eosinophilia, for 2 years, discovered on
etc.), and anti-epileptics (3: carbamazepine,
women with a mean age of 43 (18–80) CBC study for acute tonsillitis. The mean
years. The mean follow-up period was 48 valproate). ((cid:1)SD) absolute eosinophil count (AEC)
(3–152)months. sevTehree e(>ti5o0lo0g0i/elsL)ofh1y3perpeaotsieinnotspheixlihaibwitienrge was 34 843 (cid:1) 375 cells/ll and eosinophilia
Results: Most commonly involved organs of 68.61%. He had mild asthma only dur-
drug(6),HES(2),eosinophilicgastroenteri-
were peripheral nervous system (70%), ing first 5 years of life. Otherwise, he was
tis (2), Churg-Strauss syndrome (1), eosino-
lung (51%), skin (42%), and heart (21%). asymptomatic and physical examination
philicpneumonia(1),andmyeloproliferative
ANCA was detected in only 5 of 36 (14%) was normal. Rest of CBC studies, periph-
disease(1).
patients. Thirty six patients were treated eral blood smears, ESR,CRP, liver
500 ©2013TheAuthors
Allergy©2013JohnWiley&SonsA/S.PublishedbyJohnWiley&SonsLtd,68(Suppl.97),498–636
PosterSession57–Effectorcellsininflammation
function tests, serum LDH, urinalysis, Case: A 64 year-old female came to our tory pathogens and allergens. They are
repeated stool study, serum immunoglobu- hospital with acute right upper quadrant thus an integral part of the innate immune
lins, lymphocyte subsets, specific IgE for abdominal pain. She also complained of system.
inhalant allergens, chest X-ray, and dyspnea and tingling sensation of both Aim of the study: To establish 2D and 3D
abdominal ultrasound all were normal. On handsandfeet.Shehadhadchronicasthma cultures of human primary nasal epithelial
5 mg daily oral montelukast for 12 weeks, withfrequentexacerbationfor10years.An cells and to evaluate the antiinflammatory
AEC gradually decreased and remained abdominalcomputedtomography(CT)scan effect of butterbur extract (Tesalin(cid:1)), of
low (1160 (cid:1) 152 cells/ll) without the med- revealed diffuse gallbladder wall thickening which mechanisms of action are currently
icationfor6 months. and distension which was compatible with unknown.
Case 2: A 5 year boy was discovered, on acutecholecystitis.Therewasnoevidenceof Method: Biopsies were obtained from
screening workup for squint surgery, to gallbladder stones. Pulmonary function test patients undergoing turbinoplastic surgery.
have eosinophilia. He was completely showed 32% of FEV and 45% of FEV / Scratch biopsies were obtained from the
1 1
asymptomatic. He has horseshoe kidney FVC ratio.A chestCT scan revealed bron- inferior turbinates of healthy, non-atopic
and had mild virus-induced wheezing of chiectasiswithmucuspluganddiffusebron- volunteers. Scratch biopsies and Trypsin-
infancy. Physical examination was totally chial wall thickening. Nerve conduction digestedturbinateswerecultured in24-well
normal. Repeated CBC peripheral eosino- study showed mononeuritis multiflex which plates until 80% confluent and then stimu-
philia (44.3 (cid:1) 33.2%) and elevated AEC involves right hand and both feet. Initial lated with the viral stimulus Poly IC alone
(23 128 (cid:1) 18 486 cells/ll). Rest of workup peripheral blood eosinophils were increased or in combination with Tesalin(cid:1). Readouts
including hemoglobin, platelets counts, (10400/mm3). Total serum IgE was were production of IL-8 and neutrophil
ESR, serum chemistry, liver function tests, >2000 IU/mlandECPwas146 ng/ml.Stool chemotaxis. For the 3D model, a collagen/
urinalysis, repeated stool studies, serum examination for parasites and serum IgG fibroblast layer was created. On day 7, pri-
immunoglobulins, an in vitro test for panel antibodies to parasites were all negative. mary human nasal epithelial cells were
of inhalant allergens, chest X-ray, and Anti-neutrophilcytoplasmicandcardiolipin seeded on top. The model was cultured in
abdominalultrasoundallwerenormal. antibodies were negative. A bone marrow fibroblast media and moved to the air-
His peripheral eosinophil count gradu- biopsy showed normal cellularity with liquid-interface at day 13. Paraffin sections
ally reduced, over 12 weeks of 5 mg daily increased eosinophils. Fip1-like1 and plate- were stained with epithelial specific anti-
oral montelukast therapy, and remained let-derived growth factor receptor alpha bodies and analysed by immunofluores-
low(1000 (cid:1) 565 cells/ll,7.9%). gene (FIP1L1-PDGFRA) fusion was not cencemicroscopy.
Conclusion: Oral montelukast might be a detected. An echocardiogram was normal. Results: 2D cell culture could be estab-
potential therapeutic agent for primary IgEantibodiestoAspergillusfumigatuswas lished from both turbinates and scratch
peripheral eosinophilia. However, larger detected(byCAPsystem,Uppsala,Sweden). biopsies. In the 3D model, the epithelial
studiesarerequiredtoverifythiseffect. Taken all together, she was diagnosed with layer showed specific expression of Cyto-
IHES manifested as acute cholecystitis and keratins and Caveolin. Stimuation of nasal
mononeuritis multiplex. She was treated epithelial cells with Poly IC lead to
with glucocorticosteroids (1 mg/kg). Her increased production of IL-8, which was
1378 symptomswereimprovedandPFTwasnor- inhibited by Tesalin(cid:1). This effect was par-
Acaseofidiopathichypereosinophilic malised, however, peripheral eosinophil alleled by decreased neutrophil chemotaxis
syndromeaccompaniedbysuspicious counts were not normalised with the treat- towards supernatants of Poly IC/Tesalin(cid:1)-
allergicbronchopulmonaryaspergillosis ment of glucocorticosteroids for 4 weeks. treatedcells.
Choi,J-H;Hyun,I-G;Kim,C-H Then, hydroxyurea (20mg/kg) were added Conclusion: We established isolation and
HallymUniversityCollegeofMedicine,Hwaseong, and peripheral eosinophil count was nor- culture of primary human nasal epithelial
Korea malised. cells from both turbinates and scratch
biopsies. Functionality of the cells was
Idiopathic hypereosinophilic syndrome
shown by inflammatory mediator release
(HES) represents a heterogeneous group of
upon stimulation with a viral mimic and
disorders with the common features of
1380 by chemotaxis of neutrophils. Notably, Te-
prolonged eosinophilia (>1500/mm3) of an Butterburextractexerts salin(cid:1) inhibited both, Poly IC induced IL-
undetectable cause and organ system dys-
antiinflammatoryeffectsonprimary 8releaseandneutrophilchemotaxis.
functionbyeosinophilicinfiltration,predom- humannasalepithelialcellsinvitro
inantly at skin, heart, lung, gastrointestinal
tract, and nervous system. It involves gall- Steiert,S1;Zissler,U1;Chaker,A2;Bier,H2;Drewe,J3;
Zahner,C3;Schmidt-Weber,C1;Traidl-Hoffmann,C4;
bladder very often. Allergic bronchopulmo- Gilles,S1
naryaspergillosis(ABPA)isanimmunologic 1CenterofAllergyandEnvironment,Technical
pulmonarydisordercausedbyhypersensitiv- UniversityandHelmholtzCenterMunich,Munich,
Germany;2HNOKlinik,KlinikumRechtsderIsar,
ity toAspergillus fumigates inpatientswith TechnicalUniversityMunich,Munich,Germany;3Max
chronic asthma. Here we report a case of ZellerSo€hneAG,Romanshorn,Switzerland;4Klinikund
idiopathic hypereosinophilic syndrome pre- Poliklinikfu€rDermatologieundAllergologie,Technical
UniversityMunich,Munich,Germany
senting with acute cholecystitis in patients
with suspicious allergic bronchopulmonary
Background: Nasal epithelial cells repre-
syndrome.
sentthefirstlineofdefenceagainstrespira-
©2013TheAuthors 501
Allergy©2013JohnWiley&SonsA/S.PublishedbyJohnWiley&SonsLtd,68(Suppl.97),498–636
Poster Session 58
Immune regulation in the upper and lower airways
1382 12 years old, made a break for 1 month tomography. The abscesses were drained
AreportoffourcaseswithIL-12receptor treatment with IFN gamma. Following and antibiotic therapy was started. S. Aur-
B1defeciency this, presented with abscess formation eus was isolated at aspirate cultures. Right
extending to the neck under the chin. shoulder magnetic resonance imaging was
O€zkars,MY1;Keskin,O€1;Ku€c(cid:1)u€kosmanog(cid:3)lu,E1;Metin,
A2;Balcı,O3 Drainage of abscess material were sent to consistentwithsepticarthritis.Immunolog-
1PediatricAllergy,UniversityofGaziantep,G.Antep, the ARB (+). Started antibiotics relieved ical analysisofpatient revealedlow phago-
Turkey;2HematologyandOncology,Children’sHospital thepatientclinically.Follow-upcontinues. cytosis function (73.4% in granulocytes
ofPediatrics,AnkaraFieldofStudy,Immunology,
Conclusion: As well as various symptoms and 61.4% in monocytes), decreased
Ankara,Turkey;3UniversityofGaziantep,Pediatric,
G.Antep,Turkey ofpatients,severity ofdisease wasalsodif- CD4 + T-cell ratio (27.6%), low CD4 + T/
ferent.Fourcasetoo,therewasgeneralised CD8 + T ratio (0.68), increased serum IgG
Background: Mendelian susceptibility to lymphadenopathy. Three patients had per- (28.6 g/l) and increased total IgE
mycobacterial diseases (MSMD) is a rare sistent fungal infection. A serious problem (929.53 IU/ml). This case had 24 points
syndrome characterised by predisposition inourtwocasesoccurredafterBCGvacci- according to Grimbacher et al’s hyper IgE
to infections caused by weakly virulent nation, one patient with mild formed at syndromescoringsystem.
mycobacteria. Salmonellosis has been the problem occurred and no problems Conclusion: Although, hyper IgE syn-
reportedinalmosthalfofaffectedpatients. otherofourcases.Thereweretwocasesof drome is one of the PID syndromes which
Mucocutaneous candidiasis is more com- salmonella infection. A case of autoim- is frequently diagnosed in childhood, it
mon. Interleukin-12 receptor ß1 (IL- munedisease(Crohn′s)waspresent. must be considered especially in cases with
12Rß1) deficiency is the most frequent extensive staphylococcal abscesses in adult-
geneticcauseofMSMD. hood.
Method: We report four cases with IL-12
receptor B1 defeciency with different clini- 1383
calsymptoms. Septicarthritisinayoungadultwith
Results: Two patients twins. Four month hyperIgEsyndrome:acasereport 1385
old male patients. Three months after the Sayın,S1;Musabak,U2;Yesillik,S2;Tekgo€z,E1;Sarlak, Newaspectsofthepathogenesisof
BCG vaccine came with the complaint of H1;Kartal,O2;Demirel,F2;Gulec,M2;Arslan,E1; respiratorydiseasesinfrequentlyill
lymphadenopathy. Have persistent yeast Sener,O2 children
1DepartmentofInternalMedicine,GulhaneMilitary
infections in the mouth. Axillary lymph
MedicalSchool,Ankara,Turkey;2Divisionof Maleyka,K
node biopsy histology have histiocyte-rich ImmunologyandAllergicDiseases,Departmentof AzerbaijanMedicalUniversity,2ndChildrenDiseases,
active chronic inflammation and fibrosis. InternalMedicine,GulhaneMilitaryMedicalSchool, Baku,Azerbaijan
Ankara,Turkey
Patients3 yearsoldandhealthy.
Background: Bronchopulmonary pathol-
10-year-old male patient. Nine years old,
Introduction: Hyper-IgEsyndromeisa pri- ogy remains one of the most urgent prob-
bloody diarrhea, weakness, weight loss,
mary immunodeficiency (PID) syndrome lems of pediatrics. Despite multiple
and abdominal pain began. Who received
which is characterised by elevation of research papers on this problem, diseases
treatmentwiththediagnosisofSalmonella.
serum IgE, eosinophilia, sinopulmonary of the respiratory system, continue to wor-
On physical examination, neck lymphade-
infections, chronic eczema and cold skin sen,recurandswichtoachronicform.
nopathy, cachectic appearance, and there
abscesses. In this report, a case of septic Method: The aim of our study was to
wasadecreaseinsubcutaneousadiposetis-
arthritis in a young adult with hyper-IgE identify the pathogenic mechanisms respi-
sue. LAP biopsy in cervical region, non-
syndromeispresented. ratory diseases in frequently ill children
necrotizing granulomatous inflammation
Case report: A 20-year-old male patient, (FIC). To this end, were examined 340
werereportedasaresultofpathology.The
he was applied with fever, night sweats, FIC with respiratory diseases at the age of
colon biopsy showed mycobacterium avi-
um intraselu€lare. In addition, was diag- shortness of breath, left axillary, right 6 months to 6 years. In 55 FIC acute viral
nosed with Crohn′s disease. Eleven-year- shoulder and neck pain, swelling and limi- infections without complications, in 74
old patient with the diagnosis of Crohn′s tation of motion in arms. On physical FIC was observed acute bronchitis, in 175
examination: two different palpabl lesions, FIC-recurrent bronchitis and in 36 FIC
disease and severe protein energy malnutri-
oneofatthe scapular regionand theother was acute pneumonia. In patients were
tionhasbeenlost.
one at the edge of the left latissimus dorsi examined in theacute periodofthedisease
Eleven-year-old male patient. Admitted
muscle were detected. They were fluctuat- and in the period clinical remission of
with acute appendicitis. Persistent fungal
infection in the mouth of the patient′s ionfg,10hy9pe1re0mcimc, pinainsfizuel.aLndabaotraatodryiamteesttesr: nCuDm1b9e-creollfs,CtDhe3-ccoenlltse,nCtDo4f-sceerllusm,CiDm8m-cuenllos-,
medical history since the age of 5. Appen-
WBC: 16.200/mm3, erythrocyte sedimenta- globulins A, M, G,E, the content of cyto-
dectomy apandix and lymph node pathol-
tion rate: 92 mm/h. Fluid collections con- kines IL-1betta, TNF-alfa, IL-2, IL-6, IL-
ogy report and granulomatous appendicitis
sistent with abscesses were shown at right 8, IFN-gamma, the level of substance P,
diagnosed with EZN staining bacilli seen.
shoulder and the left axillary region by state of hemostasis, microbiocenosis upper
M. Tbc PCR positive. Salmonella O anti-
both ultrasonography and computed respiratorytractandintestinal.
gen 1/400 positive. Our patient was
502 ©2013TheAuthors
Allergy©2013JohnWiley&SonsA/S.PublishedbyJohnWiley&SonsLtd,68(Suppl.97),498–636
PosterSession58–Immuneregulationintheupperandlowerairways
Results: Our results show that in the acute vitro Ig production. Interestingly, the treatment with Tenofovir 300 mg for
periodoftherespiratorydisease,reducedthe mother of the patient, aged 40, presented chronichepatitisB.In2012thepatientwas
level of cellular immunity (mainly, CD3- withsimilarimmunologicalfindingsandno admitted to Internal Medicine Service of
cells, CD4-cells and the index immunoregu- historyofrecurrentorsevereinfections.We Antonio Pedro University Hospital / Flu-
lator cells), marked imbalance of humoral administered a new course of vaccination minense Federal University to investigate
immunityreductionofIgAandIgG,increase (tetanus, pertussis, diphtheria and poliovi- splenic nodules observed in abdominal CT.
ofIgMandIgE.Bythemarkedincytokine rus)tothegirlandthenmonthlyweevalu- The phisical examination demonstrated
status increase proinflammatory cytokines ated both antibody titres and T cell atipical facies, xerodermia with desquama-
IL-1betta, TNF-alfa, IL-6, IL-8, and reduc- proliferation. One month after vaccination, tionbutwithoutpruritus,absenceoflymph-
ingIL-2andIFN-qamma.Inacuteperiodof the patient showed normal antibody adenopathy and no abdominal or thoracic
the disease is marked as raising the neuro- responses, and normal T cell proliferation abnormalities. A complete blood count
peptide-substancePandbloodclotting.The responses; however, these responses gradu- revealed12 500 cells mm3whitebloodcells,
highcorrelationbetweentheimmunesystem allydecreasedandeventuallydisappearedat ofwhich25%wereeosinophils.C3was137,
including cytokine status, substance P and 5 months. In conclusion, the child and serum IgG 2169 mg/dl, IgM 216 and IgE
hemostatic system. We foundthat the clini- mother present a low antibody response to wasveryhighat34 508.Undergoessplenec-
cal remission of respiratory diseases in FIC protein vaccines, in particular to tetanus tomy and the histopatological features was
is not accompanied by a normalisation toxoid. After an adequate initial antibody granulomatous chronic inflammatory pro-
parameters of the immune system, cytokine and T cell response, no immunological cesswithextensiveareasofcaseousnecrosis.
status, substance P and hemostatic system. memory was mounted. The mechanisms of Liver with micronodular cirrhosis. The
High level of proinflammatory cytokines in such an abnormal immunological response patient is still in use of Ethambutol and
theperiodofclinicalremission,reflectongo- havenotbeencompletelyclarifiedyet.Simi- Ofloxacin, an alternative tuberculosis treat-
ing inflammation, which is associated with lar conditions have not been reported in ment,withlesshepatotoxicity.
persistence of the infection agent. Of these humans,while,inmurinemodels,theyseem Conclusion: HIES is a clinical diagnosis,
infectious in our patients revealed chla- related to deficits in signaling lymphocyte basedonagroupofclinicalandlaboratory
mydia, mycoplasma, cytomeqalovirus, activationmolecule-associatedproteins.Itis findings. This case is compatible with the
Staphylococcus aureus, Candida albicans. interesting that the patient presented with autossomal recessive form. The main
OurFICin67.6%ofcasesobserveddysbi- VCA-IgG and EBNA-IgG antibodies, teaching is the attention to the possibility
osis, the severity of which correlated indicative of a previous infection, which of diagnosis, avoiding sequelae like bron-
decreasetheimmunesystem. actuallyoccurredwithoutanycomplication. quiectasis. In this patient, the delay until
Conclusion: Given all this, it is necessary Giventhepresenceofsimilarfindingsinthe diagnosis was 30 years. There are no
to carry out adequate therapy of respira- mother, suggestive of a mendelian inheri- descriptions in the literature (PubMed) of
torydiseasesinFIC. tance,exomesequencingiscurrentlyinpro- splenic tuberculosis in HIES patients,
gress. However, the clinical impact of this drawingattentiontothispossibility.
condition is still undefined: thus, we may
only recommend that the patient undergo
1387 tetanusprophylaxistogetherwithabooster
Lackofimmunologicalresponseto vaccinedose,asindicated. 1390
proteinvaccinesinapediatricpatient Granulomatouslymphocyticinterstitial
lungdiseaseincommonvariable
Boghen,S1;Raschetti,R1;Merli,P1;Marseglia,A1;
Licari,A1;Caimmi,D1;Labo(cid:4),E1;Maccario,R1;Zuffardi, immunodeficiency:acasereport
1MOP2ae;tdMteiaoatr,rsiPcesag,vlUiiaan,,iGIvtaeLl1rys;it2yMooflePcauvliaar–MIRedCiCcSineP,oUlicnliivneicrsoitSyaonf 1H3y8p9erimmunoglobulinEsyndromewith FPierrinaluta,,DM1;MSa1;bMa,aLn2c;oMnei,lePdEd1;uD,Rel1;GMiaucscuo,,FS1R;1Frau,A1;
Pavia–IRCCSPoliclinicoSanMatteo,Pavia,Italy bronchiectasisandsplenictuberculosis 1DepartmentofMedicalSciences‘M.Aresu’,Unitof
InternalMedicine,AllergyandClinicalImmunology,
Nacife,C1;Carneiro,R1;Gismondi,R1;Verdolin,L1; UniversityofCagliari,Monserrato,Italy;2Departmentof
Case presentation: Wepresentthecaseofa Coelho,R1;Querino,A1;Moore,D1;Pestana,S2; MedicalImaging,UniversityofCagliari,Cagliari,Italy
7-year-old girl who was evaluated for sus- Boechat,JL1
pected Brown syndrome. Her blood tests 1InternalMedicine,FluminenseFederalUniversity, Background: Commonvariableimmunode-
Niteroi,Brazil;2Pediatrics,FluminenseFederal
showedalackofantibodyresponsetoteta- University,Niteroi,Brazil ficiency (CVID) encompasses a heteroge-
nus, pertussis, poliovirus, and measles vac- neousgroupofantibodydeficiencydiseases
cines, and a borderline response to the Background: A syndrome of recurrent defined by hypogammaglobulinemia, poor
diphtheriavaccine.Thesefindingswerecon- staphylococcal infections, severe eczema responses to vaccination, and recurrent
firmedafterasecondcourseofvaccination. and sinopulmonary infections was infections. About a third of these patients
She had no history of recurrent or severe described in 1966 and initially called Job show signs of autoimmunity or develop
infections. A complete immunological syndrome. This was after termed hyperim- immune-mediateddiseases.Amongthenon-
work-up showed non-protective antibody munoglobulin E syndrome (HIES), when infective complications in CVID the lung
levels for tetanus and rubella, borderline an associated increase in serum level of may be involved in the course of Sarcoido-
antibody levels for measles and diphtheria, immunoglobulinE(IgE)wasdescribed. sis-like syndromes or Granulomatous-lym-
and protective antibody levels for parotitis; Case report: E.L.S., male, 30 year. By the phocyticinterstitialdisease(GLILD).
ontheotherhand,sheshowedIgGantibod- firstyearoflife, hedevelopedeczema, with Method: We recently observed a woman
ies for EBV, CMV, VZV and HSV-1. She mild pruritus, being diagnosed and treated with history of recurrent infections of
alsopresentedlowlevelsofIgMandIgG3, asatopicdermatitis. Sincethen,thepatient upper and lower airways, which progressed
absentTcellproliferationtotetanustoxoid reports nine episodes of pneumonia, result- overtheyearsfromselectiveIgAdeficiency
(with normal proliferation to Candida and ingindilatationofthelargeairways(bron- to full-blown CVID with autoimmune hae-
mitogens),normaldistributionofTcellsub- chiectasis), recurrent skin infections with molytic anemia, nodular lymphoid hyper-
sets, borderline values of B cells able to development of pustules and recurrent her- plasia of gut and reactive lymph node
switch and switched B cells, and normal in pes zoster. Since 19 years is undergoing hyperplasia. However, since 2005 she pre-
©2013TheAuthors 503
Allergy©2013JohnWiley&SonsA/S.PublishedbyJohnWiley&SonsLtd,68(Suppl.97),498–636
PosterSession58–Immuneregulationintheupperandlowerairways
sented worsening of respiratory symptoms itemswereassessed:currentageandatdiag- Immunodeficiencies, there is a variety of
and lung infiltrates on chest X rays, which nosis, gender, occupation, family history, factors negatively impact the level of diag-
were diagnosed as Sarcoidosis and treated months on IVIG, number of infections nosis and management for Latin American
with courses of steroids, resulting in tran- before and after treatment, adverse reac- patients with Primary Immunodeficiency
sient clinical improvement followed by tionsandcomplicationsofthedisease. Diseases(PID).
multiple relapses. In 2012 we evaluated the Results: The study included 10 patients Therefore three programmes were initi-
patient, which underwent to bronchoscopy (7♂; mean age 45.40 (cid:1) 13.97 years [33– atedtoimprove thediagnosisandmanage-
and lung biopsy, finally demonstrating the 75]).Onlyonethirdwereemployed.Ageat ment of PID in Latin America: an
presence of Lymphocytic Interstitial Pneu- diagnosis: 36.50 (cid:1) 17.75 [13–71]. None of educational outreach programme (The L-
moniaandgranulomatouslesions. the patients had family history of primary Project), an immunology fellowship pro-
Results: She has been treated with steroids immunodeficiency. Seven patients were on gramme, and the establishment of a labo-
and started intravenous immunoglobulin daily medication for concurrent diseases ratory network to expand access to testing
(Ig)substitution,thenswitchedtoSubcuta- (diabetesmellitus,hypertension,pulmonary facilities.
neous Ig replacement. After 6 months a chronic disease, epilepsy). All patients were Aguascalientes is a 1.3 million inhabit-
clear improvement of symptoms and of treated with IVIG at concentrations of ants state, located 500 km. north of Mex-
infectious episodes was observed, neverthe- 400–500 mg/kg every 4 or 5 weeks admin- ico City lacking of PID clinics or referal
less chest CT showed the presence of focal istered in an outpatient setting. Median services.
areas of ground-glass attenuation, particu- treatment time was 52.50 [5–204] months. Method: As part of the mentioned pro-
larly evident in the right middle lobe. 50%ofthepatientscompliedregularly. gramsaPIDclinicwasinitiatedintheCity
Focal areas of consolidation with air bron- 50% of the patients did not have any of Aguascalientes in October 2011 receiv-
chogram were evident in the right upper adverse reactions. Three reported mild ingpatientsfromregionalhospitals,clinics,
andmiddlelobeaswellasintheleftupper reactions with shivering that required generalists and general public referrals as a
lobe. Moreover, some nodules of various decreased infusion rate. One reported an product of the educational program and
sizes, most with irregular margins and episode of fever; one had a moderate reac- public alert in the region. After several
some with associated thickening of the tion with wheezing. No severe reactions media appearances, academic lectures and
adjacent interlobular septa, were also werereported. regional hospital visits to promote PID
found.BycomparingtheCTpatterninthe Eight patients had pneumonia with hos- diagnosis and warning signs, we received
scans obtained in 2004, 2011 and 2012 we pitalisation at least twice before diagnosis. referral patients in a University based
found that the areas of ground glass atten- Of these, two had more than three epi- clinic with history of recurrent infections
uationwerenotmodifiedwhereasthenum- sodes. Along with respiratory infections, orthepresenceofatleastonewarningsign
ber and dimensions of the nodules three reported cutaneous infections and for PID. Here we describe the results of
increased. twohadgastrointestinalinfections. theprogramandtheclinicalmanifestations
Conclusion: Therapy was adjusted adding Since treatment was initiated, four and characteristics of the PIDD patients
high-dose intravenous steroids and immu- patients had a single respiratory infection diagnosed between November 2011 and
nosuppresants. GLILD or Sarcoidosis-like requiringantibiotherapy(tworequiringhos- November2012attheclinic.
syndromes or granulomatoid disorders pitalisation). One patient had two hospital Results: Twenty-four lectures were given to
could be one of the clinical presentations admissions: inaugural episode of ascites generalists,specialistsandhospitalstaffwith
of CVID patients. Treatment with steroids associated with hepatosplenomegaly and a total of 993 attendants, 12 media appear-
and IgG replacement are the mainstay of lymphadenopathy;intraperitonealabscess. ances were achieved. During the period we
treatment, being effective in most patients. The most frequent complication of the have received 151 consultations (First time
However a close clinical and radiologic disease was pulmonary chronic disease visit94,subsequent57).Thepatientsattend-
surveillanceisrequiredforthispatients. affecting four patients and four still have ing to the center were 94 male (57.6%), 57
nocomplications. female (37.7%) median age of 120 months
Conclusion: Our study confirmed that (1–708, IQR 198). The diagnosis were; PID
IVIGinpatientswithCVIDhasalowrate 15 patients (9.9%) Allergies 72 (47.6%)
1392 of adverse reactions and that is a safe pro- Other 23 (15.2%) Under investigation 41
Efficacyandsafetyofintravenous cedure. Immunoglobulin therapy reduced (27%). The PID diagnosis were; Antibody
immunoglobulininpatientswith bacterial infections and hospitalisations, as deficiencies 4/15 (33%) well defined syn-
commonvariableimmunodeficiency describedintheliterature. dromes 7/15 (47%) innate immunity defi-
Sousa,MJ;Guilherme,A;MoreiradaSilva,JP ciencies 1/15 (7%) Severe combined
ImmunoallergologyDepartment,CentroHospitalarde immunodeficiency 2/15(13%).PID patients
VilaNovadeGaia/Espinho,VilaNovadeGaia,Portugal wereeightmales(53.3%)andsevenfemales
1393 (46.6%)medianage60months(2–192,IQR
Background: CommonVariableImmunode-
Advertisingworksforprimary 102) with a mean diagnostic delay of
ficiency (CVID) is one ofthe most common
immunodeficiency.Theclinicalcenterat 44months, mean number of infections at
symptomatic primary immunodeficiency dis- theAguascalientesUniversityinMexico diagnosis6(1–24).Allpatientsarereceiving
orders.Intravenousimmunoglobulinreplace-
ment therapy (IVIG) has improved the AlvarezCardona,A1;VenturaJuarez,J2;Espinosa appropriatetreatment.
Rosales,F3 Conclusion: The frequency of PID among
clinicalcourseofCVIDbyreducingthebur- 1CentrodeCienciasdelaSalud,UniversidadAuto(cid:1)noma our series is similar to other described in
denofrecurrentinfectionsandcomplications. deAguascalientes,Aguascalientes,Mexico;2Centrode
The aim of our study was to document the CienciasBa(cid:1)sicas,UniversidadAutonomade ambulatory practice around 10%. As the
Aguascalientes,Aguascalientes,Mexico;3Instituto programgoesontheseresultsareencourag-
safetyandeffectivenessofIVIGbyreducing NacionaldePediatria,Direccio(cid:1)ndeInvestigacio(cid:1)n, ingwithatleastonePIDpatientpermonth.
theincidenceofinfections. MexicoD.F.,Mexico
Methods: A study evaluating patients with
CVIDundergoingIVIGinourdepartment, Background: As published in the proceed-
since 2011, was performed. The following ings of the Latin American Society of
504 ©2013TheAuthors
Allergy©2013JohnWiley&SonsA/S.PublishedbyJohnWiley&SonsLtd,68(Suppl.97),498–636
Poster Session 59
Immunodeficiencies
1396 ing AR. Frequencies of A/G haplotype for Method: Thirty nine patients with CVID,
Singlenucleotidepolymorphismsof TNF-a (rs1800629, rs361525) and G/G 19 patients with IGAD, and 34 healthy
proinflammatorycytokinesinallergic haplotype for IL6 (rs1800795, rs1800797) volunteers with the same ethnicity of the
rhinitis were significantly higher in the patient patient were enrolled in this study. Geno-
group. In some subgroups of patients, typing was done in all groups for one in-
Nasiri,R1,2,3;Amirzargar,AA4;Movahedi,M1;Hirbod
Mobarakeh,A4,5,6;Farhadi,E4;Behniafard,N1; there were significant relationships between tronic SNP in RAD50 (Rs2237060), using
Ansaripour,B4;Moradi,B4;Zare,A2;Rezaei,N1,4,5 IgE levels, eosinophil count, eosinophil Real-Time PCR allelic discrimination Taq-
1Children’sMedicalCenter,TehranUniversityof percentage, nature of sensitivity, persis- Mangenotypingassays.
MedicalSciences,PediatricsCenterofExcellence,
tencyandseverityofARandtheseSNPs. Results: Although the allele frequency for
Tehran,Iran;2Immunology,AsthmaandAllergy
ResearchInstitute,TehranUniversityofMedical Conclusion: Wefoundthatgeneticvariants rs2237060inRAD50wasdifferentbetween
Sciences,Tehran,Iran;3DepartmentofPediatrics, in TNF-a, IL1 gene complex and IL-6 not the patients with hypogammaglubinemia
KurdistanUniversityofMedicalSciences,Sanandaj,
only wereassociated withtherisk ofdevel- and healthy individuals, this difference was
Iran;4MolecularImmunologyResearchCenter,Tehran
UniversityofMedicalSciences,andDepartmentof oping allergic rhinitis, but also affected the not significant. There was not any signifi-
Immunology,SchoolofMedicine,Tehran,Iran; courseofdiseaseanditsseverity. cant difference in allele frequency of this
5Children’sMedicalCenter,TehranUniversityof SNP between healthy controls and both
MedicalSciences,ResearchCenterfor
Immunodeficiencies,Tehran,Iran;6Students’Scientific groups of CVID and SIgAD patients when
ResearchCenter,TehranUniversityofMedical analyzedseparately.
Sciences,Tehran,Iran 1397 Conclusion: In this study, we did not find
Normalallelesofrs2237060ofRAD50in any association between alleles of this SNP
Background: Allergic rhinitis (AR) is a
Iranianpatientswithcommonvariable withIGADorCVID.Despiteournegative
complex polygenic disorder of the upper immunodeficiencyandIgAdeficiency result, it is important to identify possible
respiratory airway with an increasing prev-
alence worldwide. As proinflammatory HirbodMobarakeh,A1,2,3;Amirzargar,AA1;Farhadi, association between CVID and IGAD and
E1,4;Nemati,S1;Nabavi,M5;Soltani,S1;Mahdaviani, variations of genes involved in class switch
cytokines, including tumor necrosis factor SA6;Shahinpour,S2;Arshi,S5;Nikbin,B1; recombination, mismatch repair system
(TNF), interleukin-1 (IL1) family and Aghamohammadi,A2;Rezaei,N1,2
interleukin-6 (IL-6) seem to be involved in 1MolecularImmunologyResearchCenter,Tehran andsomatichypermutation.
UniversityofMedicalSciences;andDepartmentof
development of allergic rhinitis, this study
Immunology,SchoolofMedicine,Tehran,Iran;
was performed to evaluate the associations 2Children’sMedicalCenter,TehranUniversityof
of single nucleotide polymorphisms (SNPs) MedicalSciences,ResearchCenterfor
ofTNF-a,IL-1familyandIL-6geneswith Immunodeficiencies,Tehran,Iran;3TehranUniversity 1400
ofMedicalSciences,Students’ScientificResearch AcaseofWiskott-Aldrichsyndromewith
AR. Center,Tehran,Iran;4HematologyDepartment,School anovelWASPgenemutation
Method: Ninety eight patients with AR ofAlliedMedicalScience,TehranUniversityofMedical
diagnosed according to modified allergic Sciences,Tehran,Iran;5DepartmentofAllergyand Yilmaz,M;Karakoc,GB;Altintas,DU;Kotil,A;Dogruel,
Immunology,Rasool-e-AkramHospital,Tehran D;Kendirli,SG
rhinitiscriteriainthe‘AllergicRhinitisand UniversityofMedicalSciences,Tehran,Iran;6Shahid CukurovaUniversity,Adana,Turkey
its Impact on Asthma’ (m-ARIA) docu- BeheshtiUniversityofMedicalSciences,Pediatric
ment were enrolled in the study and 140 RespiratoryDiseasesResearchCenter,National Background: Wiskott-Aldrich syndrome
ResearchInstituteofTuberculosisandLungDiseases
healthy volunteers with no history of AR (NRITLD),Tehran,Iran (WAS)isarareX-linkedrecessiveimmuno-
and with the same ethnicity of the patient deficiency disorder characterised by throm-
were recruited as the control group. Geno- Background: Common Variable Immuno- bocytopenia and small platelets, eczema,
typing was done for two TNF-a promoter deficiency (CVID), the most prevalent recurrent infections, and an increased risk
variants, one variant in promoter region of symptomatic primary immunodeficiency of autoimmunity and malignancy. Clinical
IL1a, two SNPs in IL1b gene, one in IL1 disease and Selective IgA Deficiency features of the disease are highly varied;
receptor and IL1RA, and two promoter (IGAD), the most common primary anti- therefore, the diagnosis is sometimes diffi-
variantsofIL-6gene,usingPCRsequence- body deficiency, both comprise heteroge- cult. The WASP gene encodes a multido-
specific-primersmethod. neous groups of disorders which represents main protein (WASP) that is expressed
Results: Patients homozygous for the T two opposite poles of humoral immunode- predominantly in hematopoietic lineages.
allele of rs16944 in IL1b had an 8.1-fold ficiency. Recently, association between The main function of WASP is to couple
risk of having AR than those with the C rs2237060 in RAD50 and these two disor- signalsgeneratedatthecellmembranelevel
allele.InTNF-a,therewerealsosignificant ders have been reported by a Swedish withthereorganizationofthecellularcyto-
relationships between two SNPs of study. Based on this finding, they sug- skeleton, ultimately resulting in cell activa-
rs1800629 and rs361525 and having AR. gestedthatasubsetofpatientswithIGAD tion and the promotion of cell motility.
Patients homozygous for the G allele of andCVIDarepredisposedtohypogamma- Approximately 400 unique mutations have
rs1800795 in IL-6 had a 3.35 fold risk of glubinemia due to variations in RAD50. been reported in the WASP gene. In this
having AR than those with the C allele. This study aimed to evaluate such an asso- study, we report a boy with classical, and
AA genotype in rs1800797 of IL6 was ciation in Iranian patients with CVID and identified a novel WASP gene mutation: a
associated with increased risk of develop- IGAD. splicingmutationIVS3-2A>G.
©2013TheAuthors 505
Allergy©2013JohnWiley&SonsA/S.PublishedbyJohnWiley&SonsLtd,68(Suppl.97),498–636
PosterSession59–Immunodeficiencies
Case: A 4-mount-old boy was admitted were evaluated for hematopoietic stem cell sidered the trigger of bronchiectasis. IFN-c
because ofrecurrent infection,bloody diar- transplantation. has a critical role in innate and adaptive
rhea, and thrombocytopenia. The family Conclusion: The hyper-IgE syndrome is a immunity against viral and intracellular
history revealed that his maternal cousin rare primary immunodeficiency disorder bacterial infections through containment
had WAS. Physical examination revealed characterised by high serum levels of IgE, and eradication of intracellular organisms,
petechiae and eczema. On laboratory recurrent skin and lung infections and ato- via macrophage activation. The case we
examination, the Hb level was 9 gm/dl, pic eczema. It is very important for pedia- describe provides additional evidence that
and the white blood cell count was tricians to contemplate atopic eczema as a a diagnosis of IFN-c deficiency should be
8.6 9 109 l, with absolute lymphocyte differential diagnosis for hyper-IgE syn- takenintoaccountinallpatientswithidio-
count 2.6 9 109 l The platelet count was drome mainly in patients born to consan- pathicbronchiectasis.
74.0 9 109 l. MPV was 7.1 fl. Immuno- guineous parents and suffering from
logic studies revealed IgG/A/M 382/ 22/ recurrentrespiratoryinfections.
55 mg/dl and IgE 6.28. Lymphocyte subset
analyses showed CD3 52%, CD19 14%, 1403
CD4 39%, CD8: 15%, CD16/56: 23%. Rapidpushsubcutaneous
Through direct sequencing of genomic 1402 immunoglobulinadministration.Asafe
DNA of the WASP gene in the patient, we IFN-cdeficiencyinadultbronchiectasis:a alternativeincaseofseveresystemic
identified a novel mutation of WASP gene casereport reactionwithintravenoustherapy
(IVS3-2A>G. Palladino,A;DiCapua,L;Ruggiero,G;Spadaro,G; Leguı´samo,S;Pin~eroSaavedra,M;Cimbollek,S
Conclusion: To our knowledge, this is the Genovese,A AllergyDepartment,HospitalVirgendelRoc(cid:1)ıo,Seville,
first report describing WAS patients with DepartmentofTranslationalMedicine,Universityof Spain
Naples‘FedericoII’,Naples,Italy
novelmutationintheWASP.
Background: Common variable immune
Background: Bronchiectasis is an irrevers- deficiency (CVID) is considered to be a
ible and abnormal dilatation of one or collection of primary immune deficiency
more bronchi, as a result of destruction of diseases (PIDD) characterised by reduced
1401
the muscles and elastic connective tissues. serumlevelsofIgG,IgA,and/orIgM,with
HyperIgEsyndromeinthedifferential
Progressive lung damage is due to the dis- reducedorabsentspecificAbproduction.
diagnosisofatopiceczema
ruption of the mucociliary clearance result- Intravenous immunoglobulin (IVIG) has
Genel,F;Gulez,N;Nacaroglu,HT;UnsalKarkiner,CS; inginretentionofsecretions,whichinturn been the preferred route of therapy but
Can,D attracts bacterial colonization with chronic subcutaneous infusion (SCIG) offers fewer
DrBehcetUzChildren’sHospital,Izmir,Turkey
inflammation. Currently, the etiology of systemic adverse events, maintains stable
Background: The mechanisms that pro- bronchiectasis remains unknown in a high serum IgG levels and can be self-adminis-
mote the enhanced susceptibility to cutane- percentageofpatients(26–53%). tered at home. Recently rapid push SCIG
ous infections in atopic dermatitis are Method: A 33-year-old non-atopic, non- administration without need of infusion
complex interactions among several fac- smoker male, was referred to our Depart- pump has been described as valid alterna-
tors.They includeskinbarrierdysfunction, ment for recurrent pulmonary infections tive. We present a patient with CIVD who
reduced skin lipid content, and abnormali- (3–4/year) and progressive lung function suffered severe systemic reactions with
ties of the innate immune response. Some deterioration despite aggressive multidrug IVIG and tolerated rapid push SCIG
of the innate immune defects observed in antimicrobial treatment. He referred dysp- administration.
atopic dermatitis are primary defects, such nea and impaired physical performance. A Method: A 41 year old patient, diagnosed
as epithelial barrier defects and defects in perimembranous interventricular septal in 2012 of CVID because of enteropathy
signaling or expression of innate receptors. defect with no significant hemodynamic and malabsorption without history of
Here we report seven cases of Hyper IgE effects was reported. Physical examination respiratory infections, started in May 2012
syndrome mainly presenting with atopic revealed bilateral basal crepitating and IVIGreposition.Hepresented10 minafter
eczema. crackles. initiating slow perfusion of third infusion
Case report: Seven patients, five born to Results: HRCT revealed cystic spaces in general feeling of discomfort, diaphoresis
consanguineous parents, were evaluated the right hemi-thorax, suggestive of bron- and hypotension. Three weeks later,
and mean age at diagnosis was 5 years. chiectasis with collapse of the right lung. despite premedication with corticosteroids
Eczematous dermatitis, mainly on face, Lung function tests revealed a mixed and antihistamines he suffered similar epi-
scalp and repeated bacterial skin and lung obstructive and restrictive pattern. Arterial sode shortly after starting infusion. Patient
infections were present in all patients. blood gases showed respiratory alkalosis. wasreferredtoourclinicinordertoevalu-
Cutaneousviralinfectionsandchroniccan- Immunoglobulins dosage and sweat chlo- ateSCIG.Thepatientwasofferedthepos-
didiasis of the nails were seen in two ride were normal. Negative sputum culture sibility of subcutaneous infusion with
patients. Facial paralysis was observed in and PPD skin test. Abdominal fat biopsy conventional pump or rapid push self-
one of the patients. All but one had high for amyloid deposits was negative. In vitro administration which is performed using a
serum IgE levels. Hypereosinophilia, and productionofIFN-cwasreduced. syringe and butterfly needle delivered over
CD4 lymphopenia were observed in all Conclusion: Bronchiectasis may be the a short period (10 min aprox.). He toler-
patients.DOCK8mutationswereidentified result of several processes. Two types of ated without any incidence 10 ml of IgG
in four patients and under evaluation in bronchiectasis are known: cystic fibrosis (160 mg/ml) per injection site (total 20 ml
three patients. Therapeutic measures (CF) and non-CF associated. COPD, post- perday/40 mlperweek).
included antibacterial and antifungal pro- infectious, congenital defects (primary cili- Results: Patient actually tolerates 60 ml
phylaxis, immunoglobulin replacement ary dyskinesia, Kartagener syndrome), per week administered subcutaneously,
therapy in all patients with interferon amyloidosis and immunodeficiency may be home based, using several infusion sites
alpha therapy in one case who presented the cause of non-CF bronchiectasis. In our per session (2–3 days/week) in abdominal
with widespread papillomas. All patients case, aberrant IFN-c secretion can be con- region. IgG levels have increased from
506 ©2013TheAuthors
Allergy©2013JohnWiley&SonsA/S.PublishedbyJohnWiley&SonsLtd,68(Suppl.97),498–636
PosterSession59–Immunodeficiencies
129 mg/dl to 405 mg/dl (40 ml/week). HRCT showed bronchiectasis of the right laboratory work revealed hypereosinophil-
Patient uses two injection sites per session, lower lobe. The results of the laboratory ia, low immunoglobulin levels with low
10 ml per injection site. Patient did not tests revealed: a leukocyte count, CD4 cell count and absence of HLA-DR
refer any local or systemic symptoms (e.g., 14.2 9 103/lL; hemoglobin, 13.4 mg/dl; expression on B cells. Mutation analysis
headache,nausea,fever). platelets, 284 9 103/ll; c-reactive protein, revealed MHC class II deficiency due to
Conclusion: SCIG using a rapid push tech- 5.54 mg/l. Immunological studies showed: mutation in the RFXAP gene. Case four,
nique with no need of pumps has demon- IgG, 398 mg/dl (610–1570); IgA, 99 mg/dl 37 day old boy presented with generalised
strated to be a safe and well tolerated (45–236); IgM, 46 mg/dl (52–242). The dry skin, eczema with cutaneous desqua-
alternative to IVIG in our patient. Rapid CD3-, CD4- and CD8-positive T cell mation. In initial investigation we found
push is a simple, flexible, with shorter infu- counts and percentages showed no specific lymphopenia, hypereosinophilia, low
sion times and no need of specialised findings. However, the percentage of immunoglobulin levels, T + B-NK+ pheno-
equipmentforhomebasedSCIG. CD19-positive B cells in peripheral blood type. His clinical and immunological find-
was only 5.5% (normal range 10–31%). ings were compatible with Omenn
She was diagnosed with CVID and was syndrome. Case five and six, 3 months old
placed on intravenous immunoglobulin boy and 3 months old girl admitted to our
1404 treatment 0.5 g/kg every 3 weeks. This hospital with pulmonary infection. They
Immunedeficiencyshouldnotbe caused a remarkable improvement in her had lymphopenia and low immunoglobulin
overlookedinchildrenwithneurological condition with a marked decrease in the levels. Flow cytometry indicated T-B-
deficits frequencyofinfections. NK + phenotype severe combined immu-
Yavuz,ST1;Arslan,M2;Unay,B2;Gok,F3;Musabak,U4 Conclusion: Although underlying neuro- nodeficiency.
1DepartmentofPediatricAllergyandImmunology, logic deficits maycausefrequent infections, Conclusion: Within this report we want to
Gu€lhaneMilitarySchoolofMedicine,Ankara,Turkey; immune deficiency should always be kept emphasize the importance of screening for
2DepartmentofPediatricNeurology,Gu€lhaneMilitary
SchoolofMedicine,Ankara,Turkey;3Departmentof in mind particularly in children who severe combined immunodeficiency in chil-
Pediatrics,Gu€lhaneMilitarySchoolofMedicine, encounter infections with unusual severity dren with lymphopenia and hypereosino-
Ankara,Turkey;4DepartmentofAdultAllergyand andcomplications. philia. In spite of treatment with IVIG
Immunology,Gu€lhaneMilitarySchoolofMedicine,
replacement therapy, cotrimoxazole and
Ankara,Turkey
antifungal prophylaxis, the poor outcome
Introduction: Recurrentinfectionsarecom- of this disease suggests urgent hematopoi-
moninchildrenwithunderlyingneurologic 1405 etic stem cell transplantation as a treat-
conditions such as cerebral palsy, mental Severecombinedimmunodeficiency: mentofchoice.
motor retardation and epilepsy. However, clinicalandimmunologicalfeaturesofsix
patientsfromasinglecenterwithina
accompanying immune deficiency may be
year
the etiological factor particularly in chil-
dren with a history of severe and/or com- Genel,F;Gulez,N;Ozbek,E;Gulez,P;Nacaroglu,HT; 1408
plicated infections. Herein, we describe a KeskinGozmen,S;UnsalKarkıner,CS;Can,D Primaryimmunodeficiencydisordersin
girl with epilepsy, mental-motor retarda- DrBehcetUzChildren’sHospital,Izmir,Turkey animmunoallergologydepartment
tion and frequent infections that were fur- Background: Severe combined immunode- Sousa,MJ;Guilherme,A;MoreiradaSilva,JP
ther diagnosed with common variable ImmunoallergologyDepartment,CentroHospitalarde
ficiencies (SCID) are the most severe forms
immunedeficiency(CVID). VilaNovadeGaia/Espinho,VilaNovadeGaia,Portugal
of primary immunodeficiencies character-
Casereport: A10-year-oldgirladmittedto
ised by the absence or dysfunction of T Background: Primary immunodeficiency
outpatient department of our unit after
lymphocytes affecting both cellular and diseases (PIDDs) are rare disorders result-
suffering throughout her childhood from
humoralimmunity. ing from inherited defects of the immune
recurrent infections. She was frequently
Case presentations: Six patients with SCID system: humoral immune deficiencies,
diagnosedwith otitis, sinusitis, andtonsilli-
wereregisteredduringtheperiodfromJan- severe combined immunodeficiencies and
tis and was hospitalised several times for
uary 2012 till January 2013 in Dr. Behcet phagocytic or complement defects. There
pneumonia. Long duration of antibiotic Uz Children′s Hospital. Two children, are more than 150 different PIDDs cur-
therapy was frequent and she was usually
50 days and 5.5 months old admitted to rently recognised by the World Health
requiring intravenous antibiotics. Although
our hospital with pulmonary infection and Organization. The aim of our study was to
she had been immunised with Varicella
skinrash.Theyhadlymphopenia,hypereo- describe the patients with PIDDs followed
vaccine, she had a severe Varicella infec-
sinophilia and decreased IgG, IgM, IgA inourdepartment.
tion when she was 8 years old. Along with
levels with reduced CD3, CD4, CD8, Methods: A study evaluating patients
the frequent infections, she had a history CD19 and CD16 + 56 positive lympho- undergoing consultation between January
of afebrile convulsions. She was still on
cytes. Metabolic findings and mutation and December 2012 was performed. A
levetiracetam and risperidon treatment analyses were consistent with ADA defi- database was designed using SPSS(cid:1)v19.0,
with diagnosis of epilepsy and mental-
ciency. The first patient underwent bone where the following items were assessed:
motor retardation. Frequent infections
marrow transplantation from an HLA age, gender, occupation, referral, family
have been attributed to her mental-motor
identical healthy sister. A matched bone historyandprimarydiagnosis.
retardation and have not been previously
marrow transplant donor could not be Results: Thirty-eight patients were
investigated in terms of immune deficiency.
found and ADA replacement therapy was included (55.3% females). Mean age:
On presentation, she had mild respiratory
initiated for the second patient. But the 41.45 (cid:1) 21.28 [1–77] years. 36.8% were
symptoms. The physical examination
patient died from pulmonary insufficiency employed, 18.4% students and 15.8%
revealed crepitant rales on right hemitho-
at the second month of ADA enzyme unemployed.
rax. The chest radiographs showed an ill-
replacementtreatment. 28.9% ofthepatientswerereferredfrom
defined opacity in the right middle and
Case three, 4 months old girl presented the Hematology Department, 23.7% from
lower lobes suggesting pneumonia. Chest
with fever and recurrent skin rash. Her Pneumology and 18.7% from Primary
©2013TheAuthors 507
Allergy©2013JohnWiley&SonsA/S.PublishedbyJohnWiley&SonsLtd,68(Suppl.97),498–636