Association of autoantibody specificity and response to intravenous immunoglobulin G therapy in immune thrombocytopenia: a multicenter cohort study

Abstract

Summary. Background: Immune thrombocytopenia (ITP) is a common autoimmune bleeding disorder, in which platelet glycoprotein (GP)IIb-IIIa and GPIb-IX are the two most frequently targeted autoantigens. Our previous studies in animal models of ITP demonstrated that intravenous immunoglobulin G (IVIG) could protect against antiGPIIb-IIIa autoantibody-mediated thrombocytopenia but failed to ameliorate ITP induced by most anti-GPIb-IX autoantibodies. Objectives: The objective of this human study was to evaluate the association between the specificity of antiplatelet autoantibodies and response to IVIG treatment. Patients/Methods: In this retrospective study, a cohort of 156 previously untreated adults with severe ITP who underwent IVIG therapy (0.4 g kg À1 day À1 for 5 days) was analyzed. The primary outcome was response defined as platelet counts of ≥ 30 9 10 9 L À1 and a doubling of baseline counts within 7 days of dosing, and an absence of bleeding. Results and Conclusions: Among the 66 patients with anti-GPIb-IX autoantibodies, only 24 (36.4%) achieved a response, as compared with 72 of 90 patients (80.0%) who were negative for anti-GPIb-IX autoantibodies (relative risk 2.2; 95% confidence interval 1.6-3.1). This study found no difference in response between patients with anti-GPIIb-IIIa autoantibodies (61.7%) and those without anti-GPIIb-IIIa autoantibodies (61.3%). Logistic regressions, including main effects and the interaction between these two autoantibodies, showed no influence of anti-GPIIb-IIIa autoantibodies on the effects of anti-GPIb-IX autoantibodies with regard to their association with IVIG response. Thus, in adults with ITP, the presence of anti-GPIb-IX autoantibodies is a predictive factor for poor response to IVIG treatment. Trial registration: ClinicalTrials.gov NCT01666795.

Successful treatment with oseltamivir phosphate in a patient with chronic immune thrombocytopenia positive for anti-GPIb/IX autoantibody

“…Studies in ITP patients and mouse models have suggested an association of anti-GPIb/IX autoantibodies with severe thrombocytopenia [3], as well as with a poor response to either intravenous IgG (IVIG) [4,5] or steroid therapy [6,7]. A recent study in a murine model of ITP suggested that anti-GPIb/IX antibodies may induce platelet desialylation, which can be treated by sialidase inhibition [8,9].…”

Immune thrombocytopenia: antiplatelet autoantibodies inhibit proplatelet formation by megakaryocytes and impair platelet production in vitro

“…[39][40][41] However the effect on proplatelet formation appears to be independent of the antibody specificity.…”

CD8+ T cells are predominantly protective and required for effective steroid therapy in murine models of immune thrombocytopenia

“…5 The primary platelet surface antigen targets are GPIIbIIIa (aIIbb3 integrin, 70-80% of patients). 2,6,7 Approximately 10% to 20% of patients do not respond to first-line therapies including steroids, 8,9 intravenous immunoglobulin G, 10,11 and anti-Rh(D). 4,10 Approximately 14% do not respond to splenectomy, and 20% of responders relapse within weeks to years.…”