Objectives. Myositis-specific autoantibodies (MSAs) are useful tools in identifying clinically homogenous subsets and predicting prognosis of patients with idiopathic inflammatory myopathies (IIM) including polymyositis (PM) and dermatomyositis (DM). Recent studies have revealed that anti-NXP2 antibody (Ab) is a major MSA in juvenile dermatomyositis (JDM). In this study, we evaluated the frequencies and clinical associations of anti-NXP2 Ab in adult IIM patients.Methods. Clinical data and sera were collected from 507 adult Japanese patients with IIM (445 adult DM, and 62 adult PM). As disease controls, 11 with JDM, 108 with systemic lupus erythematosus, 433 with systemic sclerosis, and 124 with idiopathic pulmonary fibrosis were assessed. Sera were examined for anti-NXP2 Ab by immunoprecipitation and Western blotting using polyclonal anti-NXP2 Ab.Results. Seven patients (1.6%) with adult DM and 1 (1.6%) with adult PM were positive for anti-NXP2 Ab. Except for 2 patients with JDM, no patients as disease controls were positive for this autoAb. Among 8 adult IIM patients, 3 had internal malignancies within 3 years of diagnosis of IIM. Another DM patient also had a metastatic cancer at the diagnosis. All of the carcinomas were advanced stage (stage IIIb-IV).Conclusions. While less common than in juvenile IIM, anti-NXP2 Ab was found in adult IIM. Anti-NXP2 Ab may be associated with adult IIM with malignancy.
ObjectivesWe investigated the relationships among M1 monocytes, M2 monocytes, osteoclast (OC) differentiation ability, and clinical characteristics in patients with rheumatoid arthritis (RA).MethodsPeripheral blood mononuclear cells (PBMCs) were isolated from RA patients and healthy donors, and we then investigated the number of M1 monocytes or M2 monocytes by fluorescence-activated cell sorting. We also obtained and cultured CD14-positive cells from PBMCs from RA patients and healthy donors to investigate OC differentiation in vitro.ResultsForty RA patients and 20 healthy donors were included. Twenty-two patients (55%) were anticitrullinated protein antibody (ACPA) positive. The median M1/M2 ratio was 0.59 (0.31–1.11, interquartile range). There were no significant differences between the RA patients and healthy donors. There was a positive correlation between the M1/M2 ratio and the differentiated OC number in vitro in RA patients (ρ = 0.81, p < 0.001). The ACPA-positive patients had significantly higher M1/M2 ratios in vivo (p = 0.028) and significantly greater numbers of OCs in vitro (p = 0.005) than the ACPA-negative patients. Multivariable regression analysis revealed that the M1/M2 ratio was the sole significant contribution factor to in vitro osteoclastogenesis. RA patients with M1/M2 ratios >1 (having relatively more M1 monocytes) had higher C-reactive protein and erythrocyte sedimentation rates than RA patients with M1/M2 ratios ≤1. M1-dominant monocytes in vitro produced higher concentrations of interleukin-6 upon stimulation with lipopolysaccharide than M2 monocytes.ConclusionM1/M2 monocytes imbalance strongly contributes to osteoclastogenesis of RA patients. Our findings cast M1 and M2 monocyte subsets in a new light as a new target of treatments for RA to prevent progression of osteoclastic bone destruction.
ObjectiveWe evaluated the efficacy and safety of tofacitinib in patients with rheumatoid arthritis (RA) in a real-world setting.MethodsSeventy consecutive patients, for whom tofacitinib was initiated between November 2013 and May 2016, were enrolled. All patients fulfilled the 2010 ACR/EULAR classification criteria for RA. All patients received 5 mg of tofacitinib twice daily and were followed for 24 weeks. Clinical disease activity indicated by disease activity score (DAS)28-ESR, the simplified disease activity index, and the clinical disease activity index as well as adverse events (AEs) were evaluated. Statistical analysis was performed to determine which baseline variables influenced the efficacy of tofacitinib at 24 weeks.ResultsFifty-eight patients (82.9%) continued tofacitinib at 24 weeks. Clinical disease activity rapidly and significantly decreased, and this efficacy continued throughout the 24 weeks: i.e., DAS28-ESR decreased from 5.04 ± 1.33 at baseline to 3.83 ± 1.11 at 4 weeks and 3.53 ± 1.17 at 24 weeks (P<0.0001, vs. baseline). 15 AEs including 5 herpes zoster infection occurred during tofacitinib treatment. The efficacy of tofacitinib was not changed in patients without concomitant use of methotrexate (MTX) or patients whose treatment with tocilizumab (TCZ) failed. Multivariable logistic analysis showed that the number of biologic DMARDs (bDMARDs) previously used was independently associated with achievement of DAS-low disease activity.ConclusionsOur present study suggests that tofacitinib is effective in real-world settings even without concomitant MTX use or after switching from TCZ. Our results also suggest that its efficacy diminishes if started after use of multiple bDMARDs.
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