Evidence that human autoimmune thrombocytopenia mediated by both immunoglobulin isotypes IgM and IgG is an independent disease entity.

ABSTRACT

Autoimmune thrombocytopenic purpura (AITP) is a bleeding disorder caused by clonally restricted self-reactive antibodies with specificity for platelet glycoproteins. Anti-platelet autoantibodies in AITP mainly belong to the IgG class. The occurrence of anti-platelet autoantibodies of the IgM isotype has been reported, and AITP is partially mediated by antibodies of both isotypes, IgM and IgG. Using a technique of quantitative immunoblotting of immunoglobulins on self-tissues, followed by multiparametric statistical analysis of the data, we here demonstrate that patients with IgM- and IgG-mediated AITP are readily discriminated from patients with IgM-mediated AITP as well as from patients with IgG-mediated AITP at the basis of self-reactive antibody repertoires of isotypes IgM and IgG toward non-platelet antigens of human origin. Our data suggest that, in view of the important physiological functions of self-reactive antibody repertoires, human AITP mediated by both immunoglobulin isotypes IgG and IgM may be an independent disease entity. The role of autoantibody isotype for the pathophysiology of AITP might currently be underestimated, and diagnostic and therapeutic procedures in AITP might profit from considering autoantibody isotype more carefully.