Clonal Restriction of Platelet-associated Anti-GPIIb/IIIa Autoantibodies in Patients with Chronic ITP

Results of recent studies of the pathogenesis of idiopathic thrombocytopenic purpura (ITP) have suggested activated helper T-cells drive B-lymphocytes to produce antibodies. Twenty-eight children and 85 adults with ITP entered this study. We performed polymerase chain reaction (PCR) using framework III variable region (V(H) FRIII)- and joining region (J(H))-specific primers to analyze immunoglobulin heavy-chain gene rearrangement (IgH GR) for B-cell clonality. We used multiplex PCR to analyze T-cell receptor (TCR) gamma-chain gene rearrangement (TCRgamma GR) for T-cell clonality. We diagnosed 10 cases as acute ITP and 97 cases as chronic ITP. The IgH GR result was positive in 77.8% of the acute-form cases and in 58.8% of the chronic-form cases. The TCRgamma GR result was positive in 11.1% of the acute cases and in 10.6% of the chronic cases. There was no difference in frequency of clonality between the acute and chronic forms. After treatment the platelet count normalized in 81.8% (36/44) of the chronic ITP cases with B-cell clonality and in 88.9% (8/9) of the chronic ITP cases with T-cell clonality, compared with a normalized platelet count in 46.2% (12/26) of the chronic ITP cases without clonality. The patients with T- or B-cell clonality appeared to have better therapeutic responses than patients without clonality. In conclusion, T- and B-cell clonality may play a positive role in determining therapeutic response.

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Pathophysiology and management of primary immune thrombocytopenia

Kashiwagi

Tomiyama

2013

Int J Hematol

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Primary immune thrombocytopenia, or idiopathic thrombocytopenic purpura (ITP), is an autoimmune disorder characterized by isolated thrombocytopenia due to accelerated platelet destruction and impaired platelet production. Autoantibodies against platelet surface glycoproteins, such as GPIIb/IIIa and GPIb/IX complexes, play major roles in both platelet destruction and impaired platelet production, although autoantibody-independent mechanisms, such as T cell-mediated cytotoxicity, may also be involved in its pathogenesis. Recent advances in the localization of autoantigenic epitopes and the characterization of T cell functional abnormalities in ITP patients have improved our understanding of the pathophysiology of this disease. Although corticosteroids and splenectomy remain central to the treatment of ITP, a new class of drugs, i.e., thrombopoietin receptor agonists (TPO-RAs) and rituximab, have substantially broadened the therapeutic options for refractory ITP patients. Moreover, the success of TPO-RAs in ITP patients shows that reduced platelet production caused by impaired megakaryocytopoiesis plays a greater role in ITP than previously recognized.

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Clonal Restriction of Platelet-associated Anti-GPIIb/IIIa Autoantibodies in Patients with Chronic ITP

Cited by 32 publications

References 14 publications

Autoantigens in ITP

Autoantigens in ITP

Idiopathic Thrombocytopenic Purpura: Better Therapeutic Responses of Patients with B- or T-Cell Clonality than Patients without Clonality

Pathophysiology and management of primary immune thrombocytopenia

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