Genetic risk factors for infection in patients with early rheumatoid arthritis

Abstract

We analyzed clinical and genetic factors contributing to infections in 457 subjects with early rheumatoid arthritis (RA) enrolled in a prospective, 1-year clinical trial of methotrexate and the TNF inhibitor etanercept. Subjects were genotyped for the following single nucleotide polymorphisms (SNPs): (TNF À308, À238, and þ 488); lymphotoxin-a (LTA) (LTA þ 249, þ 365, and þ 720); and Fc gamma receptors FCGR2A 131 H/R; FCGR3A 176 F/V; and FCGR3B NA 1/2 and genotypes were correlated with infections. At least one URI was noted in 52% of subjects (99/191) with the NA2/NA2 genotype of the neutrophil-specific FCGR3B gene, compared to 42% (77/181) of those with the NA1/NA2 genotype and 39% (23/59) of those with the NA1/NA1 genotype (P ¼ 0.038). Urinary tract infection (UTI) was associated with the TNF À238 A (odds ratio(OR) 2.56, 95% confidence interval (CI) 1.05-6.25) and LTA þ 365 C (OR 1.73, 95% CI 1.07-2.79) alleles, and marginally with the FCGR3A F allele (OR 1.72, 95% CI 0.99-3.00). There was a striking linear correlation between UTI and the number of risk alleles defined by these three SNPs (Po0.001), suggesting an additive effect on susceptibility. These findings have important implications for the role of genetics in susceptibility to bacterial and viral infections.

The Japanese experience with biologic therapies for rheumatoid arthritis

“…63 At present, however, consensus has not been reached as to which molecules offer truly accurate and generalizable predictions of the efficacy of biologic therapies for RA. 64,65 Many investigators are also extensively searching for factors that can predict ADR (including infections 66 and infusion reactions) associated with biologic agents by examining genetic polymorphisms in patients with RA.…”

Immunoactive prophylaxis of recurrent urinary tract infections: a meta-analysis

“…Some of these risk factors suggest possible therapeutic or prophylactic interventions. Additionally, there are diseases that seem to predispose to recurrent UTI, in particular lupus erythematosus [8] and rheumatoid arthritis [9].…”

TNF receptor I polymorphism is associated with persistent palindromic rheumatism

“…The +488A allele was not found in any (0/156, 0%) of the Chinese patients, but was found with a prevalence of 8.2% in Caucasian patients in a previous study of patients with RA (25).…”