Induction of T-cell tolerance in a patient with idiopathic thrombocytopenic purpura by single injection of humanized monoclonal antibody to CD40 ligand.

Normal B cells can be induced to express immune costimulatory molecules by activated T cells, and activated CD4 T cells can express CD40 ligand, a molecule that can engage CD40 on the B-cell surface. CD40-CD40 ligand interaction plays an important role in the pathology of certain autoimmune diseases. We report a patient with chronic idiopathic thrombocyopenic purpura (ITP) who was effectively treated with a single injection of humanized monoclonal antibody to CD40 ligand (E6040). The patient was refractory to steroid therapy, and had baseline platelet counts below 30 x 10(9)/l during the 3-month period before antibody treatment. The patient's platelet counts have increased to more than 100 x 10(9)/l long-term after E6040 administration. Platelet-associated IgG was decreased with thrombocytosis. Compared with the initial period of E6040 administration, the number of anti-GPIIb/IIIa antibody-producing B cells decreased, and proliferative response of autoreactive T cells to GPIIb/IIIa was also improved. A single injection of humanized monoclonal antibody to CD40 ligand may induce T-cell tolerance in patients with ITP.