Platelet antibodies of the IgM class in immune thrombocytopenic purpura.

Abstract

The clinical course and response to therapy of patients with immune thrombocytopenic purpura (ITP) are not completely determined by the level of IgG present on the platelet surface. It is possible that antibodies of other immunoglobulin classes also play a role in platelet destruction in some of these patients. Therefore, we studied 175 patients with ITP for the presence of IgM anti-platelet antibodies using radiolabeled polyclonal or monoclonal anti-IgM. We observed that 57% of patients with clinical ITP had increased levels of IgM on their platelets, compared with normal controls and patients with thrombocytopenia who did not have ITP (<10%), (P < 0.01). We obtained similar results using either radiolabeled polyclonal or monoclonal anti-IgM, reagents whose integrity was first characterized using erythrocytes coated with defined amounts of IgM antibody. Among patients with increased platelet-IgM there was a significant correlation both with the presence of increased platelet-C3 as well as the amount of platelet-C3 (P < 0.01, r = 0.53). We demonstrated the presence of warm-reacting IgM antiplatelet antibodies in the plasma of two of these patients who were further studied. The isolated IgM fraction from these two plasmas was able to activate complement and place 3H-C3 on normal platelets. These studies demonstrate the presence of warm-reacting IgM anti-platelet antibodies in some patients with ITP. They suggest that the binding of complement to platelets by IgM antibodies may initiate platelet clearance as well as enhance the effect of IgG antibodies in ITP.

Alterations of platelet function and clot formation kinetics after in vitro exposure to anti‐A and ‐B

“…IgM‐associated PLT activation and clearance have been reported in several disorders including immune thrombocytopenia, 32‐35 multiple sclerosis, 36 dengue viral infection, 37 and other infectious diseases 38 . Immune complexes binding to PLT Fc receptors have also been demonstrated in ITP, septicemia, and pediatric infectious diseases 38,39 .…”

“…Evidence has suggested that several PLT glycoproteins, such as GP IIb/IIIa, GP Ib, and GP V, act as target antigen sites for the attachment of these immune complexes as well 34,39,40 . Consequently, this binding activates complement system which contributes to PLT activation and clearance 32,41‐43 . Upon activation, PLTs change their spherical shape, release granule contents, aggregate, activate the coagulation process, and initiate the fibrin clot formation.…”

Emerging Concepts in Immune Thrombocytopenia

“…Most autoantibodies found in chronic ITP patients are of the IgG class, but IgM and sporadically IgA antibodies are also detected ( 100 – 102 ). IgM antibodies were shown to fix complement on platelets which could facilitate clearance, but this has not been further investigated; IgG autoantibodies seem to be the main mediator of antibody-driven autoimmunity ( 100 ).…”

“…Most autoantibodies found in chronic ITP patients are of the IgG class, but IgM and sporadically IgA antibodies are also detected ( 100 – 102 ). IgM antibodies were shown to fix complement on platelets which could facilitate clearance, but this has not been further investigated; IgG autoantibodies seem to be the main mediator of antibody-driven autoimmunity ( 100 ). Most prevalent are IgGs of the IgG1 subclass, and while IgG2, IgG3, and IgG4 subclass autoantibodies can be also found in patients, they are often accompanied by IgG1 antibodies ( 103 , 104 ).…”

Platelet‐associated IgM elevated in patients with chronic hepatitis C contains no anti‐platelet autoantibodies

“…The mechanism of thrombocytopenia in ITP is considered to be due to increased platelet destruction by anti-platelet autoantibodies, mainly anti-GPIIb-IIIa and/or anti-GPIb-IX antibodies (12,17). The autoantibodies reported most have belonged to the IgG class, and little is known about IgM autoantibodies except a few reports of elevated levels of PAIgM in ITP patients (18,19). We have reported immune-mediated cyclic thrombocytopenia caused by IgM anti-GPIIbIIIa autoantibodies (20) and, in the present paper, we have shown that elevated PAIgM is due to 'anti-platelet autoantibodies' in most of the ITP patients.…”