CC-CHEMOKINE RECEPTOR-5 POLYMORPHISM IN RHEUMATOID-ARTHRITIS

Objective. Some chemokine receptors have been shown to be co-receptors for human immunodeficiency virus (HIV-1). A 32 base pair deletion all ele in the CC chemokine receptor 5 gene (CCR5 Delta 32 allele) affects both transmission of HIV-1 and acquired immunodeficiency syndrome (AI DS)-free survival. Chemokines are suggested to be critical for establi shment of inflammatory processes in autoimmune diseases such as rheuma toid arthritis (RA), We hypothesized that the defective allele may mod ulate the inflammatory process in RA. Methods, Using polymerase chain reaction methods, we investigated the significance of the CCR5 Delta 3 2 allele in 163 Danish patients with RA and monitored clinical and par aclinical variables, Results. The gene frequency of the CCR5 Delta 32 allele (0.10) did not deviate significantly from healthy controls and from that reported in healthy Caucasian populations, nor did the distr ibution deviate from the Hardy-Weinberg predictions (131 wild type, 30 heterozygous, 2 homozygous for the deletion allele; p = 0.85). Howeve r, a significantly increased proportion of those carrying the deletion allele were negative for IgM rheumatoid factor (RF) compared to those homozygous for the normal allele (29 vs 9%; p = 0.007). The proportio n of CCR5 Delta 32 allele carriers with swollen joints was decreased c ompared to those homozygous for the normal allele (35 vs 58%, respecti vely; p = 0.03), as was the duration of morning stiffness (median 0 vs 60 min, respectively; p = 0.0002). Conclusion. The CCR5 Delta 32 alle le seems to have some influence on RA variables including RF, which su ggests that inhibition of chemokine receptors might be a potential tar get for disease modifying therapy in RA.