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To investigate the risk factors for CMV infection and to clarify the cut-off count of CMV pp65 antigenemia predicting clinical symptoms related to CMV infection in patients with rheumatic disease. We retrospectively analyzed 261 patients with rheumatic disease who were treated with immunosuppressive therapy. CMV infection was defined as positive 1 CMV-positive cell per two slides (CMV pp65 antigenemia C10/C11). Patients with CMV infection were divided into two groups based on the presence of antiviral treatment for CMV disease. We determined a cut-off value of CMV-positive cells for the diagnosis of CMV disease. CMV infection was observed in 141 cases (54%). In a multivariate analysis, CMV infection was associated with three following factors: Age 60 years (OR 1.87 [95% CI 1.04-3.36]); lymphocyte counts 1000/μL (OR 3.34 [95% CI 1.88-6.05]); steroid pulse therapy (OR 2.60 [95% CI 1.27-5.55]). The cut-off level of CMV pp65 antigenemia indicating CMV disease was five positive cells average two slides by using receiver operating characteristic curve analysis (AUC 0.95, sensitivity 0.94, specificity 0.80). Age 60 years, lymphocytopenia ( 1000/μL) and steroid pulse therapy are risk factors of CMV infection. We recommend that CMV pp65 antigenemia of 5 cells average two slides (C10/C11) in patients with rheumatic disease should be the treated with antiviral drugs.

New synthetic protocols to the nitrogen-embedded flapping molecules have been developed. Gram-scale synthesis of a key precursor, tetraamine of dibenzo[a,e]cyclooctatetraene has been established for designing flapping quinoxaline and flapping phenazineimide. The impact of the nitrogen substitution on the photophysical properties and the viscosity-probing function has been investigated in comparison with the reported flapping anthraceneimide.

Allergic asthma that is caused by inhalation of house dust mites (HDMs) is mainly mediated by Th2 cells. Recently, the roles of Sox (SRY-related high-mobility-group (HMG)-box) family members in various immune responses have been investigated. However, the roles of Sox12, a member of the SoxC group, in Th2 cell differentiation and allergic airway inflammation, remain unknown. We showed that Sox12 mRNA was significantly increased during Th2 cell differentiation. In vivo, HDM-induced eosinophil infiltration into the lung and Th2 cell differentiation were exacerbated in Sox12(−/−) mice compared with those in control Sox12(+/−) mice. In vitro, Sox12(−/−) CD4(+) T cells that were cultured under Th2 conditions had increased production of Th2 cytokines and GATA3 protein compared with those of control Sox12(+/−) CD4(+) T cells. Importantly, forced expression of Sox12 decreased the protein levels of GATA3 in CD4(+) T cells under Th2 conditions without affecting mRNA expression. Furthermore, Sox12 induced degradation of GATA3 through the proteasome pathway in CD4(+) T cells. Consistently, Sox12 enhanced ubiquitination of GATA3, which was mediated by the E3 ligase Fbw7. Finally, we found that Fbw7 knockdown partly abrogated Sox12-mediated GATA3 suppression in CD4(+) T cells. Taken together, these results suggest that Sox12 suppresses Th2 cell differentiation by accelerating Fbw7-mediated GATA3 degradation, and attenuates HDM-induced allergic inflammation.

Single-molecule spectroscopy (SMS) of a dual fluorescent flapping molecular probe (N-FLAP) enabled real-time nanoscale monitoring of local free volume dynamics in polystyrenes. The SMS study was realized by structural improvement of a previously reported flapping molecule by nitrogen substitution, leading to increased brightness (22 times) of the probe. In a polystyrene thin film at the temperature of 5 K above the glass transition, the spectra of a single N-FLAP molecule undergo frequent jumps between short- and long-wavelength forms, the latter one indicating planarization of the molecule in the excited state. The observed spectral jumps were statistically analyzed to reveal the dynamics of the molecular environment. The analysis together with MD and QM/MM calculations show that the excited-state planarization of the flapping probe occurs only when sufficiently large polymer free volume of more than, at least, 280 A3 is available close to the molecule, and that such free volume lasts for an average of 1.2 s.

We report a case of a 61-year-old man with granulomatosis with polyangiitis (GPA) complicated with refractory optic neuritis and maxillary osteomyelitis. He had been treated with prednisolone (PSL) as cryptogenic organizing pneumonia in the respiratory department for 2 years. Afterward, he complained tenderness of paranasal sinuses and rapidly progressive visual loss of the left eye. Although both MPO-ANCA and PR3-ANCA were negative, he was diagnosed as GPA based on the American College of Rheumatology 1990 criteria. Ophthalmologic and oral examination revealed left optic neuritis and destructive maxillary bone. Magnetic resonance imaging (MRI) showed the optic neuritis and inflammation around the optic nerve. This finding suggested that the direct spread of inflammation from paranasal sinuses caused the optic neuritis. In a short time, increasing a dose of PSL and administration of intravenous cyclophosphamide were initiated. Antibiotics were also administered to treat sinusitis. Although his visual acuity of the left eye deteriorated to no light perception temporarily, it finally improved after treatment and findings of MRI were also improved. In contrast, destruction of maxilla bone had been progressing. This is a rare case of GPA complicated with optic neuritis due to sinusitis and maxillary osteomyelitis.

Background: We aimed to clarify the associations of musculoskeletal inflammation patterns with peripheral blood innate lymphoid cell (ILC) populations, serum cytokine/chemokines, and treatment response to methotrexate in patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA).Methods: We enrolled patients with either RA or SpA who had peripheral symptoms and performed comprehensive ultrasound to evaluate power Doppler signals for synovitis (52 joint regions), tenosynovitis (20 tendons), and enthesitis (44 sites). We performed clustering analysis using unsupervised random forest based on the multi-axis ultrasound information and classified the patients into groups. We identified and counted ILC1-3 populations in the peripheral blood by flow cytometry and also measured the serum levels of 20 cytokine/chemokines. We also determined the American College of Rheumatology 20% improvement (ACR20) response at 3 months in 38 patients who initiated treatment with methotrexate after baseline assessment. Results: We enrolled a total of 100 patients with RA (n=66) or SpA (n=34). Synovitis was more prevalent and severer in RA than in SpA, whereas tenosynovitis and enthesitis were comparable between RA and SpA. Patients were classified into two groups which represented synovitis-dominant and synovitis-nondominant inflammation patterns, respectively. While peripheral ILC counts were not significantly different between RA and SpA, they were significantly higher in the synovitis-nondominant group than in the synovitis-dominant group (ILC1-3 p=0.0007, p=0.0061, p=0.0002, respectively). On the other hand, clustering of patients based on serum cytokine/chemokines did not clearly correspond either to clinical diagnoses or to synovitis-dominant/nondominant patterns. The synovitis-nondominant pattern was the factor that predicted no clinical response to methotrexate most significantly (p=0.0065).Conclusions: Ultrasound-detected musculoskeletal inflammation is clustered into synovitis-dominant and nondominant patterns. These patterns are associated with peripheral ILC counts and could predict treatment response to methotrexate. These data suggest that ultrasound-based inflammation patterns can be utilized to establish more individualized treatment for both RA and SpA. Trial registration: The study has been registered in UMIN Clinical Trial Registry (UMIN ID: 000033797, date of registration: 18th of August, 2018).

We treated skin sclerosis with triple therapy consisting of a glucocorticoid, intravenous cyclophosphamide, and double-filtration plasmapheresis. The objective of this study was to analyze its effectiveness in a case series of patients who received triple therapy. We enrolled 8 patients with diffuse cutaneous systemic sclerosis (dcSSc) who received triple therapy at our hospital from 2008 to 2016. We analyzed the mean change in the modified Rodnan skin score (mRSS), percentage of the predicted forced vital capacity (%FVC), percentage of the predicted carbon monoxide diffusing capacity (%DLCO), and serum KL-6 levels from baseline to follow-up. All patients were treated with an intermediate dose of oral prednisolone (30.6 ± 2.1 mg/day) initially. The mean cumulative dose of intravenous cyclophosphamide was 1.4 ± 0.2 g. The mean mRSS decreased significantly at follow-up compared with that at baseline (27.0 ± 3.3 vs 15.8 ± 3.5; P = .03). At the end of the treatment, the mean %FVC and %DLCO were improved moderately, although the differences were not significant. The serum KL-6 levels decreased from 578.9 ± 146.5 to 205.3 ± 43.1 U/ml (P = .02). No significant correlation was found between the change in mRSS or disease duration and the initial skin score severity. Triple therapy may improve skin sclerosis, with effectiveness equal or superior to other reported treatments. This preliminary case series demonstrates the potential of triple therapy for treating dcSSc. However, prospective studies with long-term follow-up should be performed to assess its role.