Background: Abatacept (ABA) is a biological disease-modifying antirheumatic drug (bDMARD) for rheumatoid arthritis (RA). The aim of this study was to identify molecules that are associated with therapeutic responses to ABA in patients with RA. Methods: Peripheral blood was collected using a PAX gene Blood RNA kit from 45 bDMARD-naïve patients with RA at baseline and at 6 months after the initiation of ABA treatment. Gene expression levels of responders (n = 27) and non-responders (n = 8) to ABA treatment among patients with RA at baseline were compared using a microarray. The gene expression levels were confirmed using real-time quantitative polymerase chain reaction (RT-qPCR). Results: Gene expression analysis revealed that the expression levels of 218 genes were significantly higher and those of 392 genes were significantly lower in the responders compared to the non-responders. Gene ontology analysis of the 218 genes identified "response to type I interferon (IFN)" with 24 type I IFN-related genes. RT-qPCR confirmed that there was a strong correlation between the score calculated using the 24 genes and that using OAS3, MX1, and IFIT3 (type I IFN score) (rho with the type I IFN score 0.981); the type I IFN score was significantly decreased after treatment with ABA in the responders (p < 0.05), but not in the non-responders. The receiver operating characteristic curve analysis of the type I IFN score showed that sensitivity, specificity, and AUC (95% confidence interval) for the responders were 0.82, 1.00, and 0.92 (0.82-1.00), respectively. Further, RT-qPCR demonstrated higher expression levels of BATF2, LAMP3, CD83, CLEC4A, IDO1, IRF7, STAT1, STAT2, and TNFSF10 in the responders, all of which are dendritic cell-related genes or type I IFN-related genes with significant biological implications. Conclusion: Type I IFN score and expression levels of the nine genes may serve as novel biomarkers associated with a clinical response to ABA in patients with RA.

Harigai (2018) Comparison of fluorescence optical imaging, ultrasonography and clinical examination with magnetic resonance imaging as a reference in active rheumatoid arthritis patients, Immunological Medicine, 41:2, 75-81, ABSTRACT Background: Fluorescence optical imaging with indocyanine-green enhancement (FOI) is a new imaging modality for the assessment of hand arthritis. The objective of this study was to compare performance profiles of clinical examination (CE), US and FOI using MRI as a reference in the same active rheumatoid arthritis (RA) patients.Methods: CE, US, FOI and MRI were performed on six subjects with active RA. Each sequence of FOI was divided into three phases based on indocyanine-green dynamics and the joints were graded semi-quantitatively. Sensitivities and specificities of CE, US and FOI were calculated using the RAMRIS synovitis score >0 as a reference in a total of 30 joints (the second to fifth metacarpophalangeal (MCP) joints and the wrist of the clinically dominant hand). Results: FOI showed sensitivities and specificities, respectively, of 85% and of 94% for Phase-1 and 69% and 94% for Phase-2. Sensitivities and specificities were 100% and 35% for CE (tender or swollen), 92% and 41% for gray scale US, and 77% and 100% for color-Doppler US. Conclusions: The performance characteristics of FOI in detection of synovitis in patients with active RA are comparable to those of US and more specific than CE. FOI has a potential as an assessment modality of RA. ARTICLE HISTORY

Abstract Objectives To investigate long-term prophylactic efficacy, drug retention, and safety of low-dose sulfamethoxazole/trimethoprim (SMX/TMP) prophylaxis against Pneumocystis pneumonia (PCP). Methods Adult patients with rheumatic diseases receiving prednisolone ≥0.6 mg/kg/day were randomized into the single-strength group (SS; SMX/TMP 400/80 mg daily), the half-strength group (HS; 200/40 mg daily), and escalation group (ES; starting at 40/8 mg and increased incrementally to 200/40 mg daily) and treated for 24 weeks, then observed for 52 weeks. The primary endpoint, the PCP non-incidence rate (non-IR) at week 24, was reported previously. The secondary endpoints were the PCP non-IR at week 52, treatment discontinuation rate, and adverse events (AEs). Results Fifty-eight, 59, and 55 patients in the SS, HS, and ES, respectively, received SMX/TMP. PCP did not develop in any of the patients by week 52. The estimated PCP non-IR in patients receiving SMX/TMP 200/40 mg daily (HS and ES) was 96.8–100%. Throughout the 52-week observation period, the overall discontinuation rate was significantly lower in HS than in SS (22.7% vs 47.2%, p = 0.004). The discontinuation rates due to AEs were significantly lower in HS (19.1%, p = 0.007) and ES (20.3%, p = 0.007) than in SS (41.8%). The IRs of AEs requiring SMX/TMP dose reduction through week 52 differed among the three groups, with a significantly higher IR in SS than in HS or ES (p = 0.007). Conclusion SMX/TMP 200/40 mg had a high PCP prevention rate and is superior to SMX/TMP 400/80 mg in terms of drug retention and safety.

Introduction: Anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab) is an autoantigen associated with dermatomyositis (DM). Anti-MDA5 Ab-positive DM patients frequently exhibit clinically amyopathic dermatomyositis (CADM), and develop rapidly progressive interstitial lung disease (RPILD). Even with early detection and potent combination immunosuppressive therapy, anti-MDA5 Ab-positive DM patients have a poor prognosis. In the present case report, we present a rare autopsy case of a patient with anti-MDA5 Ab+ DM with RPILD who exhibited diffuse alveolar damage (DAD) patterning in lung specimens, and extensive hemorrhages in multiple organs. Patient concerns: An 82-year-old Japanese man admitted with bacterial pneumonia was subsequently diagnosed with anti-MDA5 Ab-positive DM based on skin manifestations (mechanic's hand, ulcerated palmar papules, and flagellate erythema), myositis, interstitial pneumonia, and elevation of anti-MDA5 Ab titer. Diagnosis: The patient was diagnosed with anti-MDA5 Ab+ DM, complicated with RPILD. Interventions: The patient received potent immunosuppressive therapy consisting of pulse methylpredonisolone at a dose of 1000 mg for 3 days, followed by prednisolone at 60 mg/d, a 1000 mg pulse of intravenous cyclophosphamide (IVCY), and oral tacrolimus at 6 mg/d. Intravenous immunoglobulin (IVIG) at a dose of 400 mg/kg/d for 5 days was subsequently administered. Outcomes: Despite triple immunosuppressive therapy and IVIG, the patients’ respiratory status deteriorated, and the patient died of respiratory failure on the twelfth day after admission. An autopsy revealed pulmonary DAD and multiorgan hemorrhages, including the left iliopsoas muscle, gastric and bowl mucosa, spleen, and left adrenal gland. Lessons: Multiorgan hemorrhages may be a fatal complication in anti-MDA5 Ab+ DM patients.