Factors contributing to the pathogenesis of IgG‐mediated alloimmune disease

Abstract

Alloimmune diseases against blood cells can occur in pregnancy and after blood transfusions, when antibodies are formed, targeting foreign cells and tissues for destruction by myeloid cells through IgG‐Fc receptors (FcγR) in particular. In pregnancy, antibodies against human platelet or red cell antigens (e.g. Rhesus D or HPA1a) can cause life‐threatening anaemia or thrombocytopenia in the developing foetus. Here, we discuss how both the induction of those IgG antibodies and the pro‐inflammatory status of the foetus affect the effector functions through FcγR. Recent studies have found IgG glycosylation to be important with low IgG‐Fc core fucosylation resulting in increased affinity to FcγRIIIa and FcγRIIIb and thus enhanced phagocytosis and ADCC. The importance of these and other features, including oxidative stress and acute‐phase responses (C‐reactive protein, CRP) in response to infection, will be discussed and how these features may collectively synergize resulting in elevated disease pathology.