The role of CD40-CD154 interactions in autoimmunity and the benefit of disrupting this pathway

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Updated: Aug 20, 2026

Murine Model of CD40-activation of B cells
12:24

Murine Model of CD40-activation of B cells

Published on: March 5, 2010

Elias Toubi1, Yehuda Shoenfeld

  • 1Divison of Allergy and Clinical Immunology, Bnai Zion Medical Center, Haifa, Israel.

Autoimmunity
|December 29, 2004
PubMed

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.

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