Immunoglobulin G subclasses of anti‐human platelet antigen la in maternal sera: relation to the severity of neonatal alloimmune thrombocytopenia

Abstract

The monoclonal antibody immobilization of platelet antigen (MAIPA) technique was employed to detect and semiquantitatively assess total IgG anti‐HPA‐1a and its subclasses in sera of mothers who gave birth to severely thrombocytopenic (<50×109 platelets/L) (n = 14) or mildly thrombocytopenic/unaffected (>50×109 platelets/L) (n = 13) neonates. There was no statistically significant difference between the IgG anti‐HPA‐1a subclass composition of the 2 groups of sera. The majority of sera (26/27,96%) showed IgG1+IgG3 while 17/27 (63%) had all 4 subclasses of the antibody. No significant differences between the severely thrombocytopenic and mildly thrombocytopenic/unaffected groups were detected in the levels of IgG, IgG1, IgG2 or IgG4 of the antibody. However, the values of IgG3 anti‐HPA‐1a were significantly higher in the severely thrombocytopenic than in the mildly thrombocytopenic/unaffected group of sera with only little overlap (median 2.94 vs. 1.68, range 1.36–9.71 vs. 1.50–2.84, respectively; p <0.01). The results suggest that maternal IgG3 anti‐HPA‐1a has predictive value for severe thrombocytopenia of the neonate. However, a prospective study of IgG HPA‐1a subclasses in a greater number of maternal sera at different times of pregnancy is needed to test if IgG3 anti‐HPA‐1a is predictive of the degree of fetal/neonatal thrombocytopenia.

Maternal HPA‐1a antibody level and its role in predicting the severity of Fetal/Neonatal Alloimmune Thrombocytopenia: a systematic review

“…Finally, thirteen of the 27 studies had complete data , the remainder were duplicates, did not address HPA‐1a antibodies , screened all neonates or did not have a sufficient sample size . Three studies were prospective and ten studies were retrospective .…”

Factors contributing to the pathogenesis of IgG‐mediated alloimmune disease

“…FcRn is also the receptor responsible for the long half‐life of IgG (3 weeks versus 1 week for other isotypes), with the notable exception of IgG3, with a half‐life of only 1 week, accounting for the lower serum levels of this subclass. However, similar to IgG1, IgG3 is frequently observed as the principle subclass found against HPA1a and RhD and should therefore not be ignored. New insights into IgG3 polymorphisms also indicate this subclass to be even more important than previously anticipated (discussed below).…”

“…Curiously, three of the allotypic variants of IgG3, found in approximately 1% of Europeans, but up to 50% in some Asian and African countries , do actually have H at position 435 and have an extended normal half‐life in humans . The fact that this allotype can also be efficiently transported across the placenta , in conjunction with the high incidence for IgG3 responses in antigen‐specific alloimmunized mothers , makes it highly relevant to test whether the H435‐containing allotypes (also called G3m(s), G3m(s,t), or G3m15 and G3m16, respectively) are a risk factor for manifestation of clinical symptoms in alloimmune RBC and platelet reactions in pregnancy.…”

Fetal/Neonatal Alloimmune Thrombocytopenia: Pathogenesis, Diagnostics and Prevention

“…Most alloantibodies to platelets and red cells are IgG1, sometimes IgG3 or a mixture of both (Mawas et al 1997 ). Antibodies may bind complement on the opsonized target cells.…”