Effect of a single injection of humanized anti-CD154 monoclonal antibody on the platelet-specific autoimmune response in patients with immune thrombocytopenic purpura.

摘要: Blockade of the CD40/CD154 signal is a potential immunomodulatory strategy for T-cell-mediated diseases. As part phase 1, multicenter, dose-escalating trial humanized monoclonal antibody to CD154 (IDEC-131/E6040) in patients with refractory immune thrombocytopenic purpura (ITP), autoimmune response glycoprotein IIb/IIIa (GPIIb/IIIa) was evaluated at successive time points. Five each were given single infusion 2, 5, or 10 mg/kg IDEC-131/E6040 and followed 3 months. All adverse events mild, there no severe infections thromboembolic events. No increase platelet count observed treated 5 mg/kg, but an mg/kg. In only frequency B cells producing anti-GPIIb/IIIa antibodies, GPIIb/IIIa-induced T-cell proliferation, production by antigen-dependent T-B-cell collaboration all suppressed parallel after treatment, slow return baseline. contrast, irrelevant antigen not affected. These findings suggest that blockade therapy potentially effective ITP, through selective suppression autoreactive T antigens.