We examined associations between human leukocyte antigen DRB1 (HLA-DRB1) shared epitope (SE), receptor activator of nuclear factor-kappaB (RANK), RANK ligand (RANKL), osteoprotegerin (OPG), and interleukin 17 (IL-17) genotypes with age of disease onset and radiographic progression in Japanese patients with early rheumatoid arthritis (RA). HLA-DRB1 genotypes were evaluated in 123 patients with early RA (98 female, 25 male) within 1 year of symptom onset. In 72 patients, radiographic progression over a 2-year period was evaluated using Larsen's methods, and genotypes of three polymorphic sites in RANK, five sites in RANKL, two sites in OPG, and three sites in IL-17 were determined by direct polymerase chain reaction sequencing. Possession of an SE allele was significantly associated with earlier disease onset in females (median 46.9 vs 51.9 years in SE- patients; P = 0.04). Single nucleotide polymorphisms (SNPs) in RANKL (rs2277438, P = 0.028) and IL-17 (rs3804513, P = 0.049) were significantly associated with radiographic progression at 2 years. RANKL-G-, SE- patients (n = 12) had significantly less joint damage than did RANKL-G+, SE- patients (n = 11; P = 0.0038), RANKL-G-, SE+ patients (n = 21; P = 0.0018) and RANKL-G+, SE+ patients (n = 28; P = 0.0024). In Japanese RA patients, HLA-DRB1 SE alleles are associated with disease onset at an earlier age, as has been observed in Caucasian RA patients. In addition, SNPs in RANKL and IL-17 may be associated with radiographic progression in Japanese patients with early RA.

Objective. To evaluate the role of HLA-DRB1 genotypes in the development and progression of the rheumatoid arthritis (RA) disease process.Methods. Patients with polyarthritis of <1 year in duration were consecutively enrolled in the study. Other inclusion criteria were no diagnosis of inflammatory diseases other than RA, and no history of taking disease-modifying antirheumatic drugs or steroids. Patients were evaluated every 4 weeks, and radiographs of the handstwrists and feet were taken at presentation and 1 year later. HLA-DRB1 genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism methods.Results. We enrolled 198 patients (median disease duration 5.0 months) and 150 controls. The frequency of individuals with DRBl"O405 and "0410 was significantly higher in the patients than in the controls.Homozygous states for DRBl alleles with the RArelated shared epitope (SE) were associated with increased susceptibility for the development of polyarthritis (odds ratio 3.4, 95% confidence interval 1.5-7.7). None of the DRBl alleles or SE genotypes correlated with the presence of bone erosion at presentation or 1 year later.Conclusion. DRBl alleles with SEs were associated with the development of polyarthritis but not with early radiographic progression of the disease process.It is well established that certain HLA-DR alleles are associated with rheumatoid arthritis (RA) (1-3).

Febuxostat effectively reduced the concentration of urate in serum in hyperuricemic patients regardless of the level of uric acid excreted in urine without severe adverse effects.

We examined whether polymorphisms upstream of the TNF-alpha gene (TNFA) were associated with the radiological progression of rheumatoid arthritis (RA). One hundred and twenty-three patients with early RA (disease duration <1 year) were enrolled in a prospective follow-up study. The laboratory findings (ESR, CRP, and RF) were evaluated every 2 months for 2 years. Radiological progression in hands/wrists and feet was evaluated every 6 months for 2 years using Larsen's score. HLA-DRB1 genotype was determined by PCR-RFLP method. The genotypes for -1031, -863, and -857 single-nucleotide polymorphisms in the upstream 5'-flanking region of TNFA were determined by a PCR-preferential homoduplex formation assay in patients with RA and 265 healthy controls. Four TNFA alleles (U01, U02, U03, and U04) were identified. The frequency of individuals with U02 was significantly higher in patients than in controls (P = 0.0025). Radiographs of hands/wrists/feet were available for 72 patients after 1 year and for 73 patients after 2 years. When the HLA-DRB1 genotype was analyzed simultaneously, patients possessing U02 without an HLA-DRB1 shared epitope (SE) (U02+SE-) showed the lowest progression of Larsen's score (12 months). There was no difference in the level of ESR, CRP, or RF at the first visit among U02+SE+, U02+SE-, U02-SE+, and U02-SE- groups. The combination of the polymorphism of the TNFA upstream promoter region and HLA-DRB1 allele was associated with radiological progression in the early stage of RA.

Background The therapeutic goal of rheumatoid arthritis (RA) is clinical remission. However, patient characteristics associated with clinical remission by abatacept (ABT) are little known. Objectives The aim of this study is to determine the predicting factors of clinical remission induced by ABT in biologic-naïve RA patients. Methods The ABROAD (ABatacept Research Outcome as a first-line biological Agent in the real worlD) study is an ongoing prospective multicenter cohort study for investigating the efficacy and safety of ABT for treating biologic-naïve RA in the west side of Japan. Baseline profiles of the enrolled 155 RA patients (female = 83.2%, mean age at the ABT initiation = 61.3 years old, and disease duration = 8.1 years) and simplified disease activity index (SDAI) remission rate at 24 weeks were examined and then clinical factors associated with remission were determined. Anti-citrullinated protein antibodies (ACPA) titers at baseline were classified into 4 groups; negative (less than the upper limit of normal [ULN], <4.5IU/mL), low-positive (less than 3 times of the ULN, 4.5-13.5 IU/mL), high-positive (less than 22 times of the ULN, 13.6-99 IU/mL), and very high-positive (equal or more than 22 times of the ULN, >=99 IU/mL). Results SDAI remission (<3.3) was achieved in 16% of our patients. Short disease duration (<1 year) (Odds ratio [OR] = 2.79, 95% confidence interval [CI] = 1.02-7.61, p = 0.045), and very high-positive ACPA (OR = 4.44, 95% CI = 1.28-15.38, p = 0.019) were significantly associated with clinical remission at 24weeks. Also, low disease activity defined by DAS28-CRP (<2.7) at baseline (OR = 4.97, 95% CI = 0.97-25.4, p = 0.054) and male gender (OR = 2.76, 95% CI = 0.91-8.40, p = 0.072) appeared to be linked with SDAI remission. However, age at ABT initiation, concomitant use of methotrexate, CRP level at baseline, and the 1987 ACR criteria fulfillment were not statistically associated with SDAI remission. Although ACPA positivity was associated with a better response to ABT in the ORA registry (ref.), our data demonstrated that low- or high-positive ACPA was not determined as the predicting factor for remission. Conclusions Biologic-naïve RA patients with disease duration less than 1 year and very high-positive ACPA can achieve SDAI remission by ABT more frequently than without, suggesting that T cells play a critical role in synovial inflammation in such patients. References Gottenberg JE, et al. Ann Rheum Dis 2012;71:1815. Disclosure of Interest T. Fujii Grant/research support from: Bristol-Myers Squibb Japan, M. Sekiguchi Grant/research support from: Bristol-Myers Squibb Japan, K. Matsui Grant/research support from: Bristol-Myers Squibb Japan, M. Kitano Grant/research support from: Bristol-Myers Squibb Japan, M. Hashimoto Grant/research support from: Bristol-Myers Squibb Japan, K. Ohmura Grant/research support from: Bristol-Myers Squibb Japan, A. Yamamoto Grant/research support from: Bristol-Myers Squibb Japan, H. Nakahara: None Declared, K. Maeda: None Declared, A. Yokota: No...