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

Autoimmunity. Sep-Nov 2004;37(6-7):457-64. doi: 10.1080/08916930400002386.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies / immunology
  • Antibodies / therapeutic use
  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / immunology
  • Autoimmunity / immunology*
  • CD40 Antigens / immunology*
  • CD40 Ligand / immunology*
  • Dendritic Cells / immunology
  • Graft Rejection / immunology
  • Humans
  • Lymphocytes / immunology

Substances

  • Antibodies
  • CD40 Antigens
  • CD40 Ligand