Negative association between the chemokine receptor CCR5-Delta32 polymorphism and rheumatoid arthritis: a meta-analysis.

Rheumatoid arthritis (RA) is characterized by synovial inflammation mediated by T-cells, monocytes and macrophages. The homing of these cells to the inflamed synovium is regulated by chemokine-receptors and their ligands. A 32-basepair deletion (Delta32) in the gene encoding CCR5, a chemokine-receptor, results in a non-functional receptor. A negative association between CCR5-Delta32 and RA has been described, although other studies found no associations. Furthermore, the observation that individuals homozygous for CCR5-Delta32 develop RA has raised questions about the role of CCR5-Delta32. This meta-analysis of all published case-control association studies confirms the negative association between CCR5-Delta32 and RA (Odds Ratio=0.65; 95% confidence intervals=0.55-0.77; P<0.0001), suggesting that CCR5-Delta32 is protective against the development of RA. CCR5 blockade in animal models of RA results in amelioration of arthritis, suggesting that CCR5 blockade could also modify disease in patients with RA.