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Based on the efficacy of intravenous immunoglobulin (IVIg) for the treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), we developed a recombinant single-chain-fragment variable clone, VasSF, therapeutic against AAV in a mouse model (SCG/Kj mice). VasSF is thought to bind to vasculitis-associated apolipoprotein A-II (APOA2) as a target molecule. VasSF is a promising new drug against AAV, but difficulties in the yield and purification of VasSF remain unresolved. We produced monomers of new VasSF molecules by modifying the plasmid structure for VasSF expression and simplifying the purification method using high-performance liquid chromatography. We compared the therapeutic effects between 5-day continuous administration of the monomers, as in IVIg treatment, and single shots of 5-day-equivalent doses. We also evaluated the life-prolonging effect of the single-shot treatment. Two-dimensional western blots were used to examine the binding of VasSF to APOA2. Our improved manufacturing method resulted in a 100-fold higher yield of VasSF than in our previous study. Monomerization of VasSF stabilized its efficacy. Single shots of a small amount (1/80 000 of IVIg) produced sufficient therapeutic effects, including decreased glomerular crescent formation, a decreasing trend of serum ANCA against myeloperoxidase (MPO-ANCA), decreases in multiple proinflammatory cytokines, and a trend toward prolonged survival. Two-dimensional western blots confirmed the binding of VasSF to APOA2. The newly produced pure VasSF monomers are stable and therapeutic for AAV with a single low-dose injection, possibly by removing vasculitis-associated APOA2. Thus, the new VasSF described herein is a promising drug against AAV. AAV is believed to develop with ANCA production after a cytokine storm caused by microbe infection. Here, we produced completely pure and stable monomers of VasSF and then demonstrated its efficacy with a single shot of a small amount: decreased glomerular crescent formation, MPO-ANCA, and proinflammatory cytokines. In addition, the VasSF-treated group tended to survive longer than the control group. Two-dimensional western blots confirmed the binding of VasSF to APOA2 (aberrant APOA2: aberrant HDL), indicating that VasSF would be a promising drug against AAV. Graphical Abstract [ABSTRACT FROM AUTHOR]

Background During the coronavirus disease-2019 (COVID-19) pandemic, segments of the public relied on social media platforms such as Twitter for medical information shared by medical personnel. Although physicians are likely to disseminate more accurate information on Twitter than non-medical individuals, it cannot be taken for granted. As such, tweets written by physicians in Japan should also be scrutinized for accuracy. Purpose The purpose of this study was to create a profile of the most popular physician influencers on Twitter in Japan, and to do a fact-check of their tweets regarding COVID-19-related drugs. Design This is a retrospective observational study. Methods We purchased Twitter data for Japan for the initial 9 months of the COVID-19 pandemic (from January 2020 to September 2020), and extracted tweets with keywords related to COVID-19 at a sampling rate of 3%. The most popular physicians were identified and selected consecutively by searching for the top 1000 accounts using Twitter's search function. These top accounts were considered influencers and their tweets and retweets concerning COVID-19-related drugs were fact-checked against scientific literature. Results We identified 21 physician influencers with real names: most were male in their 40s and 50s working at private medical facilities. The contents of their tweets were mainly sourced from scientific publications that were current at that time. The fact-check revealed that only one of 50 tweets was not correct while the others had no identifiable inaccuracies. Conclusions Except for one tweet, tweets written and retweeted by Japanese physician influencers concerning the COVID-19-related drugs contained predominantly accurate information.   What is already known on this topic?   During the COVID-19 pandemic, Japanese physicians were likely to disseminate more accurate information on Twitter than non-medical individuals, but it cannot be taken for granted. What this study adds?   We identified 21 Japanese physician influencers on Twitter. Except for one tweet in Japanese, their tweets contained predominantly accurate information. How this study might affect research, practice, or policy?   Use of Twitter by Japanese physicians with real names will continue to be an effective means of providing rapid information. [ABSTRACT FROM AUTHOR]

Objective We aimed to clarify the clinical significance of serum levels of MMPs in interstitial lung disease (ILD) complicated with PM/DM (PM/DM-ILD). Methods We retrospectively analysed serum levels of seven subsets of MMPs in 52 PM/DM-ILD patients diagnosed at Kyoto University Hospital or Tenri Hospital from January 2005 to December 2014. The patients were sub-grouped based on the presence of anti-amimoacyl-tRNA synthetase antibody (anti-ARS antibody), anti-melanoma differentiation-associated protein 5 antibody (anti-MDA5 antibody) or lack of the antibodies (ARS-ILD, MDA5-ILD and other-ILD groups, respectively) and independently analysed. Eighteen PM/DM patients without ILD and 55 healthy control were also analysed. Associations between serum levels of MMPs and clinical findings including mortality were analysed. Results Among the MMPs analysed, MMP-7 serum levels in the ARS-ILD group were significantly higher compared with those in any of the other groups of PM/DM patients or in healthy controls. On the other hand, in the MDA5-ILD group, serum MMP-7 levels >5.08 ng/ml were associated with worse overall survival both in univariate (P = 0.017; odds ratio 18.0; 95% CI 1.69, 192.00) and multivariate (P = 0.027; odds ratio 14.60; 95% CI 1.11, 192.00) analyses. Immunohistochemical analysis suggested that MMP-7 was expressed in type II alveolar epithelial cells adjacent to the fibrotic lesions. Conclusion Serum MMP-7 levels were higher in anti-ARS antibody-positive PM/DM-ILD patients, while higher serum MMP-7 levels among anti-MDA5 antibody-positive PM/DM-ILD patients were associated with a worse prognosis. Fibrotic processes may be associated with the elevation of serum MMP-7 levels. [ABSTRACT FROM AUTHOR]

Objectives: Anti-neutrophil cytoplasmic autoantibodies (ANCA) are useful diagnostic markers in systemic vasculitic disorders with small-vessel involvement, but depending on the particular test used, the myeloperoxidase (MPO)-ANCA results are variable. In the present study, we performed a comparative analysis between our originally developed nMPO-ANCA assay that targets the native MPO antigen and other commercially available assays using sera of patients with clinical features of ANCA-associated vasculitis (AAV). Methods: Sera of 24 patients strongly suspected of having AAV were examined for the presence of MPO-ANCAs by our nMPO-ANCA assay and by other commercial-based MPO-ANCA assays. These results were correlated to indirect immunofluorescence microscopy staining patterns and patient clinical parameters. Results: Eighteen out of 24 patients (75 %) were positive for nMPO-ANCA, compared with 13 out of 24 patients (54 %) by one of the most frequently used commercial-based MPO-ANCA enzyme-linked immunosorbent assays (ELISAs) in Japan. Interestingly, the patients who tested positive with our nMPO-ANCA assay alone showed clinical features of AAV marked by continuous fever, polyarthritis, and mild nephritis. The titers of nMPO-ANCA decreased in association with clinical improvement after treatment. Conclusions: Our data suggest that a positive nMPO-ANCA result, which identifies antibodies to human native MPO antigen, correlates with AAV disease activity. Moreover, the nMPO-ANCA test has clinical utility in detecting AAV-affected patients who have tested negative using commercially available assays. [ABSTRACT FROM AUTHOR]