Toll-like Receptor 2 Variants Are Associated With Acute Reactive Arthritis

Objective. We previously reported a recent outbreak of salmonellosis in which some individuals developed complications of the enteric infection. The objective of this study was to identify genetic variants that might predispose infected individuals to develop articular and/or extraarticular sequelae after Salmonella enteritidis infection. Methods. The entire exposed cohort was invited to participate in the study by sending a saliva sample for DNA analysis. Seventy-five Salmonella-infected subjects for whom there was clinical information agreed to participate and were stratified into 4 groups. Group 1 patients had arthritis and extraarticular features, group 2 patients had arthritis alone, group 3 patients had extraarticular features alone, and group 4 patients had neither. DNA samples from an uninfected cohort of 91 normal subjects were also genotyped. Genotyping was performed using 2 Toll-like receptor 2 (TLR-2) (rs5743708 and rs5743704) and 2 TLR-4 (rs4986790 and rs4986791) single-nucleotide polymorphisms (SNPs). Statistical analyses were carried out using chi-square tests. Results. There was no association of TLR-4 exonic variants with any clinical events that were reported as accompanying the Salmonella infection. In contrast, compared with normal controls, one of the rare TLR-2 SNPs (rs5743708, R753Q) was associated with the development of arthritis and extraarticular features (P = 0.015 by chi-square test). The TLR-2 variant 753Q was not detected in any of the infected individuals with an uncomplicated course. Another TLR-2 variant, 631H, was associated with articular symptoms in infected males (P = 0.03 by chi-square test). Conclusion. In this outbreak, genetic variants of TLR-2, but not TLR-4, were associated with acute reactive arthritis following infection with S enteritidis.