Autoimmune diseases are considered to result from an interplay of genetics, environment, and the immune system itself. The genetic component of rheumatoid arthritis (RA) has been estimated as conferring approximately 60% of disease risk, with previously identified genetic associations having been found for the human leukocyte antigen (HLA) locus, as well as for the PTPN22 and CTLA4 genes. These genetic regions all are involved in T-cell-mediated immune responses. In contrast, the tumor necrosis factor (TNF) receptor-associated factor 1 (TRAF1) gene is involved in the signaling cascade of the proinflammatory cytokine TNF, and the C5 gene plays a central role in complement-related protection against pathogens. These two genes occupy adjacent loci on chromosome 9q33-34 and are also thought to be involved in the onset and perpetuation of inflammation, Ms. Kurreeman explained during her presentation at the annual European Congress of Rheumatology. The TRAF1-C5 locus has already been implicated in the development of RA in a Dutch case-control study of 290 patients with the disease and 254 unaffected controls (PLoS Medicine. 2007;4:e278). “We previously found that this region has an odds ratio of about 1.2-1.3 for rheumatoid arthritis, which, as with many genes involved in susceptibility to complex disease, is a modest effect,” said Ms. Kurreeman, a PhD student at Leiden (the Netherlands) University Medical Centre. “We also observed that the effect was predominantly seen in patients who harbored autoantibodies, suggesting that this locus might be involved in other autoimmune diseases as well,” she said. Accordingly, genotyping of the variant defining the signal peak was performed in Spanish and Dutch sample sets that included a total of 862 patients with type 1 diabetes, 1,049 patients with celiac disease, 367 patients with systemic sclerosis, and 746 patients with systemic lupus erythematosus (SLE). Some 2,442 healthy, ethnically matched unrelated subjects were controls. Significant associations of the A allele of TRAF1-C5 were seen for type 1 diabetes, with an odds ratio of 1.16, and SLE, with an odds ratio of 1.18. Significant associations were not seen for systemic sclerosis or celiac disease, with odds ratios of 1.04 and 1.10, respectively. The associations with diabetes and SLE were replicated in an analysis of another sample set from Crete that included 99 patients with type 1 diabetes and 223 controls, as well as 272 patients with SLE and 259 controls, yielding odds ratios of 1.56 and 1.50, respectively. Furthermore, the association has also been found for the development of juvenile idiopathic arthritis (JIA), with a 1.5-fold increased risk, as was seen in a case-control study that included 338 patients with JIA and 511 healthy controls. The association was strongest for polyarticular JIA, with an odds ratio of 1.46 (Ann. Rheum. Dis. 2008 July 1 [doi:10.1136/ard.2008.089060]). “This gene probably lies in a common pathway that predisposes to autoimmune disease, and may provide a basis for insight into underlying mechanisms of disease. In the long run, we hope to identify genetically at-risk patients earlier, and develop improved therapies and possibly cures,” she said during a press conference. Ms. Kurreeman received a European League Against Rheumatism Young Investigator Award for this work. She disclosed no conflicts of interest.