The role of CD40-CD154 interactions in autoimmunity and the benefit of disrupting this pathway.
Many tissue injuries and immune mediated pathologies such as graft allo-rejections were found to involve CD40-CD40 ligand (CD40L, CD154) signaling pathway. The disruption of this pathway in many animal models led to the improvement of graft survival in these models. CD40-CD154 interactions were also shown to play a significant role in the maintenance of autoimmunity, and the production of auto-antibodies in systemic lupus erythematosus (SLE). High-level expression of CD154 has been detected on T cells from patients with active SLE, rheumatoid arthritis (RA) and other autoimmune diseases, indicating that such cells could account for the high-level expression of immune accessory molecules on B cells of patients with active disease. An increased serum level of soluble CD154 was also reported in SLE, RA, and Sjogren's disease in correlation with the relevant auto-antibodies and with the clinical disease activity. Anti-CD154 antibody therapy prevents auto-antibody production and renal immune complex deposition in lupus nephritis, indicating that disruption of this pathway could be a beneficial treatment in SLE. However, the etiology of the higher than expected number of thromboembolic events in anti-CD154 treated SLE patients should be investigated and preventive measures should be considered.
Toubi
Elias
E
Divison of Allergy and Clinical Immunology, Bnai Zion Medical Center, Haifa, Israel.
Shoenfeld
Yehuda
Y
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology*; D023201:CD40 Ligand / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D008214:Lymphocytes / Q000276:immunology
D000906:Antibodies; D019013:CD40 Antigens; D023201:CD40 Ligand