Individuals with rheumatoid arthritis frequently have autoantibodies to citrullinated peptides, suggesting the involvement of the peptidylarginine deiminases citrullinating enzymes (encoded by PADI genes) in rheumatoid arthritis. Previous linkage studies have shown that a susceptibility locus for rheumatoid arthritis includes four PADI genes but did not establish which PADI gene confers susceptibility to rheumatoid arthritis. We used a case-control linkage disequilibrium study to show that PADI type 4 is a susceptibility locus for rheumatoid arthritis (P = 0.000008). PADI4 was expressed in hematological and rheumatoid arthritis synovial tissues. We also identified a haplotype of PADI4 associated with susceptibility to rheumatoid arthritis that affected stability of transcripts and was associated with levels of antibody to citrullinated peptide in sera from individuals with rheumatoid arthritis. Our results imply that the PADI4 haplotype associated with susceptibility to rheumatoid arthritis increases production of citrullinated peptides acting as autoantigens, resulting in heightened risk of developing the disease.

Rheumatoid arthritis is a common autoimmune disease characterized by chronic inflammation. We report a meta-analysis of genome-wide association studies (GWAS) in a Japanese population including 4,074 individuals with rheumatoid arthritis (cases) and 16,891 controls, followed by a replication in 5,277 rheumatoid arthritis cases and 21,684 controls. Our study identified nine loci newly associated with rheumatoid arthritis at a threshold of P < 5.0 × 10(-8), including B3GNT2, ANXA3, CSF2, CD83, NFKBIE, ARID5B, PDE2A-ARAP1, PLD4 and PTPN2. ANXA3 was also associated with susceptibility to systemic lupus erythematosus (P = 0.0040), and B3GNT2 and ARID5B were associated with Graves' disease (P = 3.5 × 10(-4) and 2.9 × 10(-4), respectively). We conducted a multi-ancestry comparative analysis with a previous meta-analysis in individuals of European descent (5,539 rheumatoid arthritis cases and 20,169 controls). This provided evidence of shared genetic risks of rheumatoid arthritis between the populations.

The low-signal intensity changes on T1-weighted sequences indicated a poor prognosis. The authors speculate that high-signal intensity changes on T2 weighted images include a broad spectrum of compressive myelomalacic pathologies and reflect a broad spectrum of spinal cord recuperative potentials. Predictors of surgical outcomes are preoperative signal intensity change pattern of the spinal cord on radiologic evaluations, age at the time of surgery, and chronicity of the disease.

We concluded that fall rates in RA patients were higher than in the general population and that balance impairment or side effects of drugs may play a role in increasing the risk of falls.

Objective. To evaluate medial radial displacement (MRD) of the medial meniscus in osteoarthritic (OA) and normal knees, with and without weight bearing, using ultrasonography (US), and to prospectively evaluate the time course of changes in MRD in OA knees.Methods. The study subjects were 78 patients with OA of the knee (69% female; mean age 66.4 years) and 20 healthy, asymptomatic subjects (70% female; mean age 64.5 years) who served as a control group. The OA stage was determined according to the Kellgren/ Lawrence (K/L) radiographic grading system. US measurement of MRD was performed with subjects in the supine and standing positions. With the exception of subjects who dropped out, 58 OA knees (followup rate 74%) were evaluated at baseline and ϳ1 year later.Results. The medial meniscus was significantly displaced radially by weight bearing in control knees (P < 0.001) and in knees with K/L grades 1-3 OA (P < 0.01 for each comparison). MRD in either the supine or the standing position was not significantly different between the control knees and the K/L grade 1 knees, but significant differences were noted between the control knees and K/L grade 2 or more severe OA knees (P < 0.01 for each comparison). MRD of the medial meniscus had increased significantly on followup in all knees (P < 0.05 for each comparison) excluding K/L grade 4 knees in the standing position.Conclusion. MRD of the medial meniscus increased with weight bearing and during followup. These findings suggest a close association between extraarticular displacement of the medial meniscus and progression of OA.