Functional CCR5 Receptor Protects Patients With Arthritis From High Synovial Burden of Infecting Chlamydia trachomatis

Abstract

IntroductionThe CCR5 chemokine receptor occurs in a wild-type (wt) and a nonfunctional deleted form (Δ32). Reports suggested that Chlamydia-induced reproductive tract pathology is attenuated in women bearing Δ32. The authors asked whether the mutation affects synovial prevalence and burden of Chlamydia trachomatis. MethodsPolymerase chain reaction (PCR) defined CCR5 genotype in synovial tissue DNA from 218 individuals: 21 controls, 110 with reactive arthritis (ReA), 83 with undifferentiated oligoarthritis (UO), 4 with osteoarthritis (OA). Disease durations were 0.5 to 21 years. Additional PCR assays defined the presence of C trachomatis DNA. Bacterial load was assessed by real-time PCR in selected samples. ResultsFive controls were wt/Δ32, 16 were wt/wt; 2 of 21 controls (both wt/wt) were PCR positive for C trachomatis. Eighty-five (44%) patients with arthritis were PCR positive for C trachomatis (69 ReA and 16 UO). For patients with ReA, 14 (13%) had wt/Δ32, 10 (71%) of whom were PCR positive. Nineteen patients with UO (23%) were wt/Δ32, with 1 (1%) PCR positive. No differences existed for gender or other factors. One patient with OA had wt/Δ32. In ReA and UO samples, wt/Δ32 heterozygotes had a 5- to 10-fold higher bacterial burden than did wt/wt patients (P=0.03), regardless of diagnosis. ConclusionThese results indicate that the wt/wt genotype is associated with attenuated synovial bacterial load compared with loads in wt/Δ32 patients. Although no alleles other than Δ32 were assessed, our data suggest that this allele provides little/no protection from ReA in patients infected with Chlamydia- but it may provide some protection in patients with UO. The basis of this possible differential effect of CCR5 genotype is under study.