Human Blood Groups and Antibodies Phyllis Patricia Moores Doctor of Science

600 Pages·2012·13.05 MB·English

Human Blood Groups and Antibodies
Phyllis Patricia Moores
Nat. Dip. Med. Lab. Tech (S.A.) B.S.c. (Bristol)
M.Sc. (Natal) Ph.D. (Natal)
Submitted in partial fulfilment of the
requirements for the degree of
Doctor of Science
in the
Department of biological Sciences
Faculty of Science
University of Natal
Durban
December 1991
Frontispiece
SOUTH AFRICANS
i i
ABSTRACT
The following blood group phenotypes and antigens were studied:
A Ax, Ayt B., B.-like, B -like, "Bombay" Oh Le(a+b-),
bantu, 3
"Bombay" 0h Le(a-b-), para-Bombay, Mi(a+), Vw+, S-s-U-, Dantu,
Gerbich-, P H, STEM+, Rh:-34, Rh Le(a-b-c-d-), McC(e+) and
1 null,
Wd( a+) and a new form of polyagglutination associated with
haemoglobin M - type Hyde Park. The effect of inheriting a y,
D--, De- or R1Li haplotype was also investigated.
••
The following blood group antibodies were studied: anti-N in a
person with type MN red cells, anti-hrS anti-Rh34, anti-Jsb and
,
anti-To Type M red cells were confirmed to absorb anti-N and
type N red cells not to absorb anti-Me
A new ' technique w.as described for separating the two red cell
populations in twin chimeras. Three XX/XX female dispermic
chimeras with blood of two genetic types, two with patchy skin
pigmentation, were identified. Reduced I and enhanced i
antigen expression hel ped confirm a case of congenital
dyserythropoietic anaemia type II. Oval red cells accompanying
an r (dee) haplotype were found, and anti-Tja-like haemolysins
were not detected in women about to abort.
Aspects of haemolytic di sease of the newborn due to ABO and Rh
antibodies were discussed. Two new tests in which 2-mercapto
ethanol was used to distinguish between IgG (7S) and IgM (19S)
immunoglobulins were described. Blood group phenotype and gene
frequency studies were made in Black, White, Indian and
Coloured blood donors and the results were presented in 32
tables. Thirty monoclonal anti-A and 96 monoclonal antibodies
for antigens in the ABO, MNSs, Rh, Lutheran, Kell, Lewis and
Kidd systems and for other antigens were investigated for their
activity and specificity.
iii
PREFACE AND ACKNOWLEDGEMENTS
This thesis includes all my original and co-authored
publications to date, some original but still unpublished
studies from my M.Sc. (1976) and Ph.D. (1981) theses, and
thirty-two recently formulated tables containing the results of
my blood group phenotype and gene frequency studies in blood
donors of the Natal Blood Transfusion Service. The frequencies
in the Black donors are from my M.Sc. thesis, those in the
White donors from the same thesis, in which they were included
as the control group, those in the Indian donors from my Ph.D.
thesis and those in the Coloured donors from a published paper
and another accepted for publication but that has not yet
appeared in print. None of this work has been submitted in any
form for any degree or diploma to any University other than the
University of Natal. All the investigations since 1961 were
made at the Natal Blood Transfusion Service and Natal Institute
of Immunology, where I am employed as a full-time staff member.
The chapters begin with a list of my publications relevant to
each title. This is followed by a short introduction in which
the earlier related work is briefly reviewed. Commentaries on
the the papers are then furnished, in the form of summaries.
The thesis concludes with a brief resume of the rare and
interesting blood groups and conditions identified in southern
Africa.
Born in Bournemouth, England, in 1927, I travelled extensively
around Africa as a child with my parents. My father was a
wireless engineer on foreign service for Cable and Wireless, a
British telecommunication company. After having matriculated
in Salisbury (now Harare), Southern Rhodesia (now Zimbabwe) in
1944 and having studied pharmacy for two years at the British
Naval and British Army hospitals in Alexandria, Egypt, I was
taken to England and enrolled as an undergraduate at Bristol
University. In 1949, the University awarded me the degree of
Batchelor of Science. Later in the same year, I rejoined my
parents, who by now had settled in Durban, and was employed by
the Natal Provincial Pathological Laboratory Service as its
iv
first post-graduate medical technology student. In 1951, the
South African Medical and Dental Council awarded me its
National Diploma in Medical Laboratory Technology (Clinical
Pathology), and I was registered as Medical Technologist No.
27. After two years as Technologist in Charge, Rhesus
Laboratory, I entered t he Natal Blood Transfusion Service
(NBTS) as Technologist in Charge, crossmatching and Antenatal
Laboratories, Addington Hospital. Early in 1955, following my
parents' divorce, I returned to England. During the first six
months in London, Professor J.V. Dacie employed me as a senior
medical technologist in his Special Haematological
Investigations laboratory at the Post-graduate School of
Medicine, Hammersmith Hospital. Dr R.R. Race and Dr R. Sanger
then kindly asked me to join them in the Blood Group Research
unit at the Lister Institute in Chelsea Bridge Road. Two very
happy and productive years were spent with them as their senior
research assistant; this was also a most exciting time ,to be
engaged in blood group serology. It is my earnest hope that my
subsequent work has been worthy of this excellent training and
experience. The next four years were passed in Salisbury
(Harare) as a medical technologist in the private pathological
laboratory of Dr G.V. Blaine. Among general haematological,
parasitological, biochemical and other studi,es, I was
responsible for all the antenatal investigations and for
grouping and crossmatching the blood donations for the local
Blood Transfusion Service. In 1961, my mother having become
terminally ill, I returned once more to Durban, where I was
fortunate enough to be asked by Dr B. G. Grobbelaar, then
Medical Director of the Natal Blood Transfusion Service, to
found and develop a Special Investigations Laboratory for
advanced blood group and antibody studies. In 1976, the
University of Natal awarded me the degree of Master of Science
for my thesis entitled "The Blood Groups of the Natal Negro
People", and I was promoted to the position of Scientific
"
Officer. In 1981, the University of Natal awarded me the
degree of Doctor of Phi losophy for my thesis entitled "The
Blood Groups of the Natal Indian People". By now I had been
employed as Head of the Red Cell Serology Reference Laboratory
at the NBTS for some years. Late in 1987, I was transferred to
v
the newly-created Immuno-Haematology Reference Laboratory at
the Natal Institute of Immunology (Research Division of the
NBTS); and this is my position at present.
since 1965, papers and/or posters have been presented at all
except one of the National Blood Transfusion Congresses and at
other congresses and meetings in South Africa. Papers and/or
posters were also presented in 1972, 1975, 1978, 1982, 1984,
1986, 1987 and 1990 at International Blood Transfusion and
other Congresses and meetings overseas. In 1988 and 1990, I
was invited to attend and took part in the preliminary
investigations for the First and Second International Workshops
on Monoclonal Antibodies, which were held in Paris, France, and
in Lund, Sweden, respectively.
After 30 years of very happy and productive work in Natal,
during which many opportunities arose to make interesting and
meaningful blood group studies, I can truthfully say that my
career has been a most satisfying and scientifically rewarding
one. Natal, with its four main populations: Black, White,
Indian and Coloured, has been, and still is, a splendid place
in which to have engaged in these investigations. The all
absorbing interest which the groups raised, however, was not
the only reason for studying them; they also had real practical
importance. When patients with rare groups and antibodies
needed blood urgently, it was essential to find donors with the
same rare groups quickly. Through knowing the donors with rare
blood groups personally and where they might be found, these
loyal men and women, most of whom subsequently became members
of the Rare Donor File, frequently came to the rescue by
providing donations of their compatible blood. Their co
operation has been very much appreciated.
I would like to thank Dr J.C. Thomas, late Medical Director,
Natal Provincial Pathological Laboratory service, for having
provided me with my first opportunity to group blood when he
appointed me Head of this Service's Rhesus Laboratory in 1951.
I am also deeply indebted, as already described, to the late Dr
R. R. Race and to Dr R. Sanger, Blood Group Research Unit,
vi
London, who inspired in me a deep and long-lasting love for
blood group research. without them, and their continued help
and advice, I would not have achieved so much.
To Dr P. Brain, recently retired Medical Director, Natal Blood
Transfusion Service, lowe immense thanks for his sustained
encouragement and advice: no-one could have a better friend.
Dr G.H. Vos, Natal Institute of Immunology, who for some years
was almost the only person with whom I could converse in the
intricate language of blood group serology, was a respected
comrade until he retired in 1988. Mr L. V. Milner, my immediate
superior and colleague, stoically and patiently endured my
abundant joys, sorrows and tears. Mrs Elizabeth Smart, who
ably assisted me from 1976 to 1987, is still a most loyal and
devoted colleague. I thank her, most sincerely, for having
allowing me to make good use of her technical skill. To the
multitude of staff members, blood donors and patients who so
willing supplied me with samples of their blood and saliva on
numerous occasions, my many co-authors, colleagues and friends
in other Blood Transfusion Services and laboratories throughout
South Africa and the world, I give my most heartfelt thanks.
This has been a lifetime of incredible interest and excitement,
and it will be a wrench to have to leave it so soon upon
retirement.
I would like to thank Professor C. Fernandez-Costa, Medical
Director and Chief Executive of the Natal Blood Transfusion
Service, the Executive Committee of this Service and Dr J.
conradie, Director of the Natal Institute of Immunology, for
having kindly given me permission to prepare and present this
thesis. I am also deeply grateful to Miss C. Ouwerkerk, Miss
T. Barham, Mrs F. Green, Dr M. Bubb and Mr D. Stubbings, and to
Mr S. Gengaya and his staff in the printing department, for
their part in its production.
Lastly, but by no means least, I must thank the good Lord
sincerely for having provided me with the necessary health,
strength, skill and persistance to investigate the fantastic
array of interesting blood samples that He constantly showered
vii
upon me. At times, the samples arrived so fast that, until
now, few if any moments remained to publish papers about them.
It seemed more appropriate to identify each problem quickly,
find compatible blood and provide the sender with a reasonably
detailed report.
~P
Durban, December 1991. Phyllis Patricia Moores
viii
CONTENTS
Page
ii
Abstract
iii
Preface and acknowledgements
viii
Contents
xvii
publications
Papers and posters presented at South African
National Blood Transfusion Congresses and other
xxiii
congresses and meetings in South Africa
xxvii
Tables
xxx
Map of southern Africa
I THE ABO SYSTEM
1
1.1 PAPERS AND STUDIES
1.2 INTRODUCTION 2
1.3 COMMENTARY 2
1.3.1 Attainments in London, 1955 to 1957 2
1.3.2 Attainments in Durban, 1961 to 1991 2
1.3.2.1 Subgroups of A 2
1.3.2.2 Subgroups of B 4
1.3.2.3 The "Bombay" Oh phenotype 4
1.3.2.4 Para-Bombay phenotypes 6
A gene, y, modifying the blood group antigen A 8
The A subgroups of the ABO blood group system 21
Subgroups of A and AB in Natal Negroes 31
Weak group A variant phenotypes in the Natal Indians 43
Weak group B variant phenotypes in the Natal lndians 53
The first "Bombay" Oh person in South Africa 79
Red cell and serum studies in the first family
to have been recorded in which both Oh Le(a+b-)
and Oh Le(a-b-) siblings were represented 88
ix
Page
Haemagglutination inhibition studies for the
evaluation of blood group antigens in ethanol
soluble substances (ESS) obtained from human,
baboon and Vervet monkey red blood cells 105
Haemagglutination inhibition studies of water
soluble blood group substances recovered from
the erythrocytes of classical "Bombay" Oh subjects 111
Some observations on "Bombay" bloods, with
comments on evidence for the existence of two
different Oh phenotypes 117
Serological studies of anti-A+B+H allo-antibodies
in the sera of three Natal "Bombay" Oh Indians 124
Para-Bombay phenotypes in the Natal Indians 137
II THE MNSs SYSTEM
11.1 PAPERS 153
11.2 INTRODUCTION 154
11.3 COMMENTARY 155
11.3.1 Attainments in London, 1955 to 1957 155
11.3.1.1 M and N antigens and antibodies 155
11.3.1.2 The antigens Mia and Vw 155
11.3.2 Attainments in Durban, 1961 to 1991 155
11.3.2.1 The U- phenotype 155
11.3.2.2 MN with anti-N 157
11.3.2.3 Dantu 157
Notes on some reactions of human anti-M and
anti-N sera 160
Blood group antigens Mia and Vw and their
relation to the MNSs system 169
On the relationship of the blood group antigens
Mia and Vw to the MNSs system 171
A comparative study between the S-s-U- phenotype
found in Central African Negroes and the S-s+U
phenotype in Rh individuals 182
null
Four examples of the S-s-U- phenotype in an
Indian family 188