Platelet autoantibodies (IgG, IgM, IgA) against glycoproteins IIb/IIIa and Ib/IX in patients with thrombocytopenia

Abstract

Autoimmune thrombocytopenic purpura (AITP) is most frequently induced by platelet-specific autoantibodies against epitopes on platelet GP Ib/IX or GP IIb/IIIa. These antibodies are reliably detected on the patients' autologous platelets. So far, studies on the characterization of platelet autoantibodies have been restricted to IgG antibodies. We used the monoclonal antibody immobilization of platelet antigens assay (MAIPA) in a modified version to detect GP-specific IgG, IgM, and IgA antibodies. Platelets of 46.2% of patients carried elevated amounts of IgG antibodies. IgM and IgA antibodies were observed less frequently and showed only weak OD signals in the MAIPA assay. Circulating IgG antibodies in serum were found in 11.5% of patients. Circulating IgM autoantibodies were observed in 8.9% and IgA antibodies in no patient with AITP. Results of direct MAIPA assay were compared with the reactivity of eluates in the platelet adhesion immunofluorescence assay and were found to be highly concordant. Patients with AITP in remission carried high percentages of anti-GP IIb/IIIa. Findings made in this study suggest that autoantibodies of the IgM and IgA classes play only a minor role in the pathogenesis of AITP.

High-dose cyclophosphamide with autologous lymphocyte–depleted peripheral blood stem cell (PBSC) support for treatment of refractory chronic autoimmune thrombocytopenia

“…Furthermore, in agreement with the report by Kiefel et al, clinical responses in our group were not uniformly associated with decreases of elevated GPIb or GPIIIa antibodies. 3 Thus, autoimmune responses against platelet antigens other than GPIb or GPIIIa may account for some AITP cases and may also be amenable to this therapy. 2 T lymphocytes probably play an important role in the initiation and maintenance of platelet autoimmunity in some patients.…”

“…Hematopoietic recovery was supported with G-CSF at 5 g/kg/d by daily intravenous infusion until the absolute neutrophil count (ANC) exceeded 500/mm 3 for 3 successive days. Prophylactic antimicrobial therapy (norfloxacin 400 mg orally twice daily and fluconazole 400 mg orally or intravenously daily) was administered until the ANC exceeded 500/mm 3 . Trimethoprim/sulfamethoxazole 160/ 800 mg orally twice daily on 2 days weekly and acyclovir 200 mg orally 4 times daily or 250 mg/m 2 intravenously daily were given from day 0 to day 90.…”

“…[1][2][3][4] In contrast to childhood acute postviral immune thrombocytopenia, AITP in adults is usually chronic, idiopathic (occasionally associated with rheumatologic or lymphoproliferative diseases), and frequently refractory to treatment. 5,6 Nearly one third of patients fail to respond to standard treatment with corticosteroids, intravenous immunoglobulin (IVIg), or splenectomy.…”

Chronic Idiopathic Thrombocytopenic Purpura: Mechanisms of Pathogenesis

“…The trigger for the initiating autoantibody response is unknown, although autoreactive T helper (Th) cells that interact with antibody-producing B cells are required [3]. Platelet-associated autoantibodies are detected in 50%-70% of patients with ITP [17][18][19], emphasizing the limitations of the currently available assays and/or suggesting that other or additional mechanisms are involved. A quantitative assay for nonspecific platelet-associated IgG had a positive predictive value of only 46% in patients with ITP and it could be detected in disease states other than ITP, including hematologic malignancy and infection [20].…”

“…A quantitative assay for nonspecific platelet-associated IgG had a positive predictive value of only 46% in patients with ITP and it could be detected in disease states other than ITP, including hematologic malignancy and infection [20]. Assays for antibodies targeting gpIIb-IIIa, gpIb-IX, and gpIIa-IIIa may be more specific [17,18,21], but have limited sensitivity, and the diagnosis remains dependent on clinical presentation for the most part.…”