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.

The Isotype of Autoantibodies Influences the Phagocytosis of Antibody‐Coated Platelets in Autoimmune Thrombocytopenic Purpura

“…Porcelijn and von dem Borne [37] mentioned an occurrence of anti‐platelet autoantibodies of the IgM isotype in up to 26% of cases. This observation was previously confirmed by our group, indicating that AITP is mediated partially by antibodies of both isotypes, IgM and IgG [38]. In some clinical settings, the detection of IgG autoantibodies might not be sufficient.…”

Immunoglobulin M antiplatelet autoantibodies from mice immunized with rat platelets induce thrombocytopenia and platelet function impairment

“…23 Moreover, our data point towards several different questions that require additional investigation. First, in addition to IgG autoantibodies, human IgM antiplatelet autoantibodies are pathogenic, 24 suggesting that our mouse IgM autoantibodies can be used for pathogenicity studies. In particular, phagocytosis of platelets opsonized by IgM autoreactive antibodies may be analyzed with these mAbs, which has not yet been extensively done with this autoantibody isotype.…”

Advances in pemphigus and its endemic pemphigus foliaceus (Fogo Selvagem) phenotype: A paradigm of human autoimmunity

“…They are often an indicator of a recent infection or re-infection with viral diseases such as rubella [59], infectious mononucleosis [60] or hepatitis B [61], bacterial infections such as Lyme disease [62], or parasitosis such as toxoplasmosis [63, 64]. Natural IgM antibodies against self-antigens have been reported in autoimmune diseases such as lupus erythematosus [65–68] autoimmune hemolytic anemia [69], and autoimmune thrombocytopenia [70]. Some have proposed that anti-Ro IgM autoantibodies in lupus may represent part of the natural IgM repertoire that leads to production of pathogenic IgG autoantibodies by epitope spreading in genetically predisposed individuals [65].…”