The IgG subclasses of platelet‐associated autoantibodies directed against platelet glycoproteins IIb/IIIa in patients with idiopathic thrombocytopenic purpura

Abstract

Summary. The majority of patients with idiopathic thrombocytopenic purpura (ITP) have antiplatelet autoantibodies that are most frequently directed against platelet glycoproteins IIb/IIIa or Ib/IX/V. However, there is some debate whether the immune response is oligoclonal or polyclonal in nature. We investigated the subclass distribution of anti-IIb/IIIa IgG autoantibodies in 59 prospectively studied patients with ITP. We also tested patients with a variety of thrombocytopenic disorders (n ¼ 31) and healthy controls (n ¼ 30). Platelet lysates were tested for IgG anti-IIb/IIIa autoantibodies, and the specific IgG subclass distribution was measured using antigen capture assays. All testing was done blinded to diagnosis and other assay results. After unblinding, we found that 43 of the 59 ITP patients had anti-IIb/IIIa autoantibodies (sensitivity ¼ 73%). Anti-IIb/IIIa autoantibodies were also detected in five of the 31 non-ITP patients, but in none of the 30 healthy controls (specificity ¼ 91%). The IgG subclass assay was positive in 39 of the 43 ITP patients with anti-IIb/IIIa antibodies (sensitivity ¼ 92%) and in 12 samples that had no detectable anti-IIb/IIIa antibodies including two ITP patients (specificity ¼ 83%). The most common subclass in the ITP patient samples was IgG1 (77%), either alone (n ¼ 14) or with other IgG subclass antibodies (n ¼ 19). However, there were also patients with only IgG2 (n ¼ 2), IgG3 (n ¼ 3) or IgG4 (n ¼ 3) antibodies. Our results are consistent with the hypothesis that ITP is a heterogeneous disorder and that some patients have evidence of oligoclonality, whereas other patients have polyclonal autoantibodies.

Overlap of IgG4-related Disease and Primary Biliary Cirrhosis Complicated with Autoimmune Thrombocytopenia

“…Patients with ITP have anti-PLT autoantibodies that are most frequently directed against PLT glycoproteins IIb/IIIa or Ib/IX/V. Chan et al (25) reported that the most common subclass of anti-IIb/IIIa antibodies in ITP patients was IgG1. Murase et al (22) reported an IgG subclass of a PLT antibody to be potentially IgG4.…”

Helicobacter pylori eradication shifts monocyte Fcγ receptor balance toward inhibitory FcγRIIB in immune thrombocytopenic purpura patients

“…An expression level of FcγRII on monocytes was first identified as one of factors associated with H. pylori infection in ITP patients by flow cytometric analysis using a mAb that reacts with both FcγRIIA and FcγRIIB, but this association was later shown to be primarily attributable to inhibitory FcγRIIB based on 2 different assays: quantitative PCR (14,15). It has been shown that anti-GPIIb/IIIa Abs in ITP patients are predominant of the IgG1 subclass (16), which has the highest affinity for FcγRII (13). Thus, FcγRs expressed on macrophages in the RES apparently play a central role in 2 aspects of the pathogenic process: platelet destruction and sustained autoimmune responses to the platelet antigens.…”

Combined immune thrombocytopenic purpura and immunoglobulin A nephropathy: a similar pathophysiologic process?

“…In ITP, an abnormal autoantibody that is usually immunoglobulin G (IgG) with specificity for one or more platelet membrane glycoproteins (GPs) binds to circulating platelet membranes. [10][11][12] In a previous study, it was determined that the PDGF levels are elevated in patients with ITP. 13 In this article, we presented a case that presented both IgAN and ITP, and examine the possible pathophysiological relationship.…”