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Autoimmune hemolytic anemia (AIHA) Sacha Zeerleder, MD PhD Internist – hematologist Department of Hematology Academic Medical Center Amsterdam Department of Immunopathology, Sanquin Research, Amsterdam [email protected] Autoimmune hemolytic anemia (AIHA) AIHA is characterized by an increased breakdown of red blood cells (RBC) due to autoantibodies (auto-Ab’s) with/without complement activation. Pathogenesis AIHA AIHA is characterized by an increased breakdown of red blood cells (RBC) due to autoantibodies (auto-Ab’s) with/without complement activation. RBC antigens Ineffective antigen presentation • Rh-related polypeptides • Immature DCs • Molecular mimicry • Decreased co-stimulatory help by T- • Oxidative changes in RBC antigen cells structure? AIHA Complement system Functional B/T cell abnormalities • Altered expression of CR1 • Polyclonal lymphocyte activation • Decreased experssion membran- • Alteration of cytokine profile boud complement regulators (CD59) • Dysregulation of T-Regs Diagnosis AIHA AIHA is characterized by an increased breakdown of red blood cells (RBC) due to autoantibodies (auto-Ab’s) with/without complement activation. Laboratory analyses: • Hemolysis (LDH , haptoglobine , hyperbilirubinemia) • Positive Coombs • (reticulocytosis) Specificity of autoantibodies: • Rhesus antigen (50% in AHIA with warm autoantibodies) • I/i antigen (AHIA cold antibodies) • P-antigen (paroxsysomal cold hemoglobinuria) But: biological activity of the autoantibody determines the clinical activity rather then than the specificity of the autoantibody AIHA: biological activity of autoantibodies Isotype autoantibody: determines complement activation and Fc gamma receptor binding Complement activation: • IgM: most efficient • IgG1, IgG3: efficient • IgG2, IgA: weak • IgG4: no complement activation Fc-gamma receptors • IgG1, IgG3 FcgRI (CD64) • IgG (low affinity) FcgRIIa AIHA: complement activation C1s C1r C1s C1r AIHA: complement activation C2 C4 C1s C1r C2a C4b AIHA: complement activation C3c C3 FI C3c C3b C3d C3b C3d AIHA: complement activation C5 C6 C7 C5b C8 C3b AIHA – destruction of autologous RBCs RBC-lysis Complement activation CR receptor depositie Fc-gamma receptor

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Autoimmune hemolytic anemia (AIHA) Sacha Zeerleder, MD PhD Internist – hematologist Department of Hematology Academic Medical Center Amsterdam

Autoimmune hemolytic anemia (AIHA) - Swisstransfusion PDF

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Autoimmune hemolytic anemia (AIHA) Sacha Zeerleder, MD PhD Internist – hematologist Department of Hematology Academic Medical Center Amsterdam

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Publication Year:	2012
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Language:	English
File Size:	5.45
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