CD40-CD154 interaction augments the expression of inflammatory cytokines and MMP in chondrocytes and contributes to an intrinsic process of cartilage degradation in RA.
CD40-CD154 interaction is an important mediator of inflammation and has been implicated in T helper type 1-mediated autoimmune diseases including rheumatoid arthritis (RA).
Although CD40 has recently been identified in genome-wide association study as a novel rheumatoid arthritis susceptibility gene such an association has not been documented for SLE.
Although blockade of the CD40-CD40L pathway with BI 655064 in MTX-IR patients with RA resulted in marked changes in clinical and biological parameters, including reductions in activated B-cells, autoantibody production and inflammatory and bone resorption markers, with a favourable safety profile, clinical efficacy was not demonstrated in this small phase IIa study.
CD40 rs1883832 is associated with decreased risk of Graves' disease, especially in Asian; CD40rs1883832 is associated with increased risk of multiple sclerosis; CD40 -1C>T (rs1883832) is not associated with the susceptibility of Hashimoto's thyroiditis, systemic sclerosis or Asthma; there is insufficient data to fully confirm the association between CD40rs1883832 and systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Behçet's disease (BD), myasthenia gravis (MG), Crohn's disease (CD), ulcerative colitis (UC), Sarcoidosis, Fuch uveitis syndrome (FUS), Vogt-Koyanagi-Harada syndrome (VKH), Kawasaki disease (KD), giant cell arteritis (GCA) or Immune thrombocytopenia (ITP).
In conclusion, our data suggest that therapeutic CD40-CD40L blocking agents may prove efficacious not only in early and established RA, but also in inhibiting the progression of the disease from arthralgia or UA to RA.