Genetic susceptibility and the link between cat exposure and rheumatoid arthritis

Abstract

Objectives: Rheumatoid arthritis (RA) is a chronic inflammatory disease for which immunogenetic susceptibility factors have been defined. In a recent case control study, it was shown that a prior intimate relationship with pet cats or budgerigars confers risk for subsequent development of RA after a period of latency. Pets are a potential reservoir for putative microbial agents that could be a stimulus for chronic inflammation subject to the influence of immunogenetic factors. Therefore, a study was undertaken to determine whether the presence of HLA-DRB1 alleles bearing the RA susceptibility motif influenced risk for RA associated with prior exposure to pets. Methods: Blood samples were obtained from available RA patients and their case controls who had participated in the prior epidemiologic study. DR and DQ genotypes were determined by sequence analysis of oligonucleotides amplified from the DRB1 and DQB1 genes by polymerase chain reactions (PCR). Subjects were segregated according to pet exposure (as determined previously) and genotype for statistical analyses. Results: The odds ratio (OR) for prepubertal exposure to cats and RA in available subjects irrespective of DRB1 genotype was 4.2 (CI, 2.1 to 8.5; P <.00002). The OR between prior exposure to cats and RA in subjects with the RA susceptibility genotype DRB1 *0401 and *0404 was 5.8 (CI, 1.4 to 26; P <.02) and >24 (CI, 1.6 to 813; P <.01), respectively. In subjects with the genotype DRB1 *1501, the association between RA and prior cat exposure was OR 8.4 (CI, 1.7 to 45; P <.01). No significant association between RA and pet exposure was found in patients selected according to other genotypes. The association between RA and the recognized HLA-DR susceptibility motif was slightly stronger in subjects with a history of intimate cat exposure (OR 4.7 [CI, 1.5 to 14.8], P <.005) than subjects without prior intimate exposure (OR 3.3 [CI; 1.2 to 9.3], P <.02). In the small number of subjects who had reported an intimate association with pet birds, no influence of DR genotype on risk for RA was discerned. Conclusions: Risk for RA associated with prior intimate exposure to cats is concentrated in subjects with the RA-susceptibility conferring genotypes DRB1 *0401 and *0404. The findings suggest an interaction between an environmental agent associated with pet cats and certain RA susceptibility-conferring DR genotypes. The risk for RA associated with intimate cat exposure also was significant in subjects with DRB1 *1501, a genotype not otherwise associated with RA, but which shares with known RA susceptibility-bearing alleles the presence of an electropositive pocket (Pocket 4) in the DR peptide binding groove.