Lmmunobiology of human anti‐lgA: a serologic and immunogenetic study of immunization to IgA in transfusion and pregnancy*

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Abstract
Human antibodies to human IgA are detected by a sensitive passive hemagglutination assay using IgA paraproteins. The antibodies have a dichotomy of specificities: (1) class‐specific with titers frequently higher than 1:1000 produced by persons lacking IgA, and (2) antibodies with limited specificity (titers less than 1:256) produced by persons with normal IgA when repeatedly transfused. Either type of anti‐IgA belonging to the IgG class was present in 86 per cent of the patients with anaphylactoid and urticarial transfusion reactions, which was consistent with binding of the complement by such antibodies. Anti‐IgA antibodies were detected in 16 per cent of the cases with multiple transfusions received during openheart surgery procedure; they also have a significantly high incidence in the sera of recently delivered women. One fetus had IgM anti‐IgA, probably as a result of immunization to maternal IgA. Serum obtained from a Caucasian woman before and after an anaphylactoid reaction to a blood transfusion contained anti‐IgA antibodies of limited specificity of the IgG class, possibly as a result of isoimmunization in pregnancy. The patient's serum was used as an agglutinator in passive hemagglultination assays on normal serum, which resulted in the definition of Am(l), the first genetically determined allotype of human IgA. On the basis of serologic and immunochemical evidence, Am(1) was localized in the a chains. Based on its gene frequencies and on family studies, Am(l) was established as a mendelian dominant trait. The isoantigen is associated with γA2 subclass but not with the serum γA2 levels. Am(1) is different from the other allotypes of human immunoglobulins, the Gm and Inv types. Am(1) is detectable in salivary IgA; it was not detectable in cord sera. Its polymorphism makes it suitable for studies of population genetics and the molecular biology of IgA.