Functional CCR5 receptor protects patients with arthritis from high synovial burden of infecting Chlamydia trachomatis.

INTRODUCTION: The 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.
METHODS: Polymerase 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.
RESULTS: Five 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.
CONCLUSION: These 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.