NIAMS has supported several significant advances in rheumatic diseases through GWAS of simple case-control design. A recent study published in Nature Genetics by the International Consortium for Systemic Lupus Erythematosus Genetics (SLEGEN) identified several susceptibility variants in women with systemic lupus erythematosus (SLE), including ITGAM, PXK, and KIAA1542.5
Other studies in SLE found an association with two novel alleles, C8orf13-BLK and ITGAM-ITGAX.6 Genetic studies of the src family tyrosine kinase BLK gene suggest that BLK tyrosine kinase contributes to B-cell tolerance mechanisms. ITGAM is a protein in the integrin alpha chain family, is expressed by several myeloid cells, and mediates interactions between immune cells.
Studies in RA through the North American Rheumatoid Arthritis Consortium continue to identify risk loci in RA.7 NIAMS-supported investigators genotyped more than 300,000 single nucleotide polymorphisms (SNPs) from 1,522 patients with RA and 1,850 matched controls and found that a common genetic variant at the TRAF-1C5 locus on chromosome 9 is associated with an increased risk of anticyclic citrullinated peptide-positive RA.
NIAMS investigators Kastner and Elaine Remmers, PhD, collaborated with NIAMS-supported investigators to explore the role of STAT4 and the risk of RA and SLE. They found a SNP haplotype in STAT4 associated with increased susceptibility to both RA and SLE. The fact that both RA and SLE share a common risk allele hints at the possibility that the two diseases share similar pathways.8
Childhood Arthritis and Rheumatology Research Alliance
These days, clinical research is predominantly a multidisciplinary, multisite endeavor. NIAMS supports several studies that utilize national networks and provide the infrastructure for pursuing large, multicenter studies—or, in the case of rarer diseases, smaller, multicenter studies.
One of these networks is the Childhood Arthritis and Rheumatology Research Alliance (CARRA), which has a mission to improve the care of children with rheumatic disease with high-quality clinical research. Through CARRA, NIAMS is supporting several large-scale clinical trials, including the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) trial, the Early Aggressive Therapy in Juvenile Idiopathic Arthritis (JIA) trial, the Safety and Effectiveness of Rilonacept for Treating Systemic Idiopathic Arthritis (RAPPORT) trial, and the Rituximab in Myositis (RIM) trial.
APPLE is studying the effects of atorvastatin (Lipitor) on lipid levels, inflammation, and the development of atherosclerosis in pediatric lupus patients. The Early Aggressive Therapy in JIA trial is comparing the effectiveness of aggressive drug regimens in treating children with poly-JIA, one of the more severe types of JIA. Specifically, the study will determine whether aggressive therapy started in the first six months of disease onset can result in inactive disease and clinical remission while patients are taking these medications.
