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Lessons learned from anti-CD40L treatment in systemic lupus erythematosus patients

Division of Rheumatology, Clinical Immunology and Allergy, University of Crete, Medical School, Heraklion, Greece

D T Boumpas

Division of Rheumatology, Clinical Immunology and Allergy, University of Crete, Medical School, Heraklion, Greece, boumpasd{at}med.uoc.gr

The CD40-CD40L system has pleiotropic effects in a variety of cells and biological processes including immune response, thrombosis and atherogenesis. Within the immune system, these molecules representa critical link between its humoral and cellular arms. As a result of these attributes and based on preclinical data in animals, anti-CD40L antibodies were tested in a variety of immunologic diseases including idiopathic thrombocytopenic purpura, psoriasis, Crohn’s disease, systemic lupus erythematosus and transplantation.Phase I/II studies in humans with lupus nephritis demonstrated reduction of anti-double-strandedDNA (anti-dsDNA) antibodies but not of protective antibodies. Reduction of anti-DNA was associated with increased serum complement levels and reduced glomerularinflammation. As a result of thromboticeffects, observed even in patients negative for anti-cardiolipinantibodies, there is a temporary halt on further human studies. The reasons for the prothrombotic effects are not clear at present but may represent effects on platelets and/or the endothelium. In view of the significant immunomodulatory effects of anti-CD40L treatment in patients with lupus nephritis, the increasing realizationof the importance of premature atherosclerosis in lupus and an increasing amount of data supportinga role for the CD40-CD40L interactionsin this process, inhibition of this pathway deserves further exploration in lupus.

Key Words: anti-CD40L • BG9588 • CD154 • CD40 • CD40L • IDEC-131 • systemic lupus erythematosus

Lupus, Vol. 13, No. 5, 391-397 (2004)
DOI: 10.1191/0961203304lu1032oa


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