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Objectives To characterize clinically distinct subgroups among unselected patients with anti-synthetase antibodies using cluster analysis. Methods This study evaluated patients with anti-synthetase antibodies registered to two independent cohorts; 106 consecutive patients from a prospective, single-centre cohort of the Scleroderma/Myositis Centre of Excellence (SMCE) were used as a derivation cohort and 125 patients from the Multicentre Retrospective Cohort of Japanese Patients with Myositis-Associated Interstitial Lung Disease (JAMI) were used as a validation cohort. Anti-synthetase antibodies were identified by RNA immunoprecipitation. A multiple correspondence analysis followed by hierarchical clustering was performed to aggregate the patients into homogeneous subgroups. Subsequently, a simple-to-use classification tree was generated using classification and regression tree analysis. Results Three clusters were identified in the SMCE cohort: cluster 1 (n  = 48), the interstitial pneumonia with autoimmune features/amyopathic dermatomyositis cluster, associated with older age at diagnosis and a higher frequency of malignancy; cluster 2 (n  = 46), the DM cluster, corresponded to a younger age at diagnosis with a higher prevalence of myositis, arthritis, DM pathognomonic rashes, mechanic's hands and fever; and cluster 3 (n  = 12), the SSc cluster, characterized by chronic interstitial lung disease. There was no significant difference in overall survival or progression-free survival between the clusters. A simple classification tree using myositis and RP was created in the SMCE cohort. Clusters 1 and 2 were successfully reproduced and the classification tree demonstrated favourable performance in the JAMI cohort. Conclusion Patients with anti-synthetase antibodies were classified into three distinct phenotypes, indicating substantial heterogeneity within this patient group. [ABSTRACT FROM AUTHOR]

Objective: To develop a multianalyte assay for the detection of dermatomyositis (DM)-related autoantibodies using immunoprecipitation (IP) combined with immunoblotting (IB). Methods: Sera from 116 DM patients were subjected to RNA and protein immunoprecipitation assays as well as commercial enzyme-linked immunosorbent assays (ELISAs) for anti-aminoacyl transfer RNA synthetase, anti-melanoma differentiation antigen 5 (MDA5), anti-Mi-2, antitranscriptional intermediary factor-1γ (TIF-1γ), and anti-U1 ribonucleoprotein antibodies. The IP/IB assay was developed by immunoprecipitation of autoantigens from HeLa cell extracts using patient sera, followed by immunoblotting with an antibody against Mi-2, TIF-1γ, OJ, nuclear matrix protein (NXP)-2, MDA5, PM/Scl, small ubiquitin-like modifier activating enzyme (SAE), or Ku. A multianalyte assay was designed by mixing primary antibodies in the IP/IB assay. Results: IP assays identified any DM-related autoantibodies in 100 patients (86%), of which 82% were covered by commercial ELISAs, with a false-positive result in two sera and a false-negative result in one serum. The results obtained from the multianalyte IP/IB assay and ‘goldstandard’ IP assays were concordant in terms of the presence or absence of anti-MDA5, anti-TIF-1γ, anti-OJ, anti-NXP-2, anti-PM/Scl, anti-SAE, anti-Mi-2, and anti-Ku antibodies. Conclusion: This multianalyte IP/IB assay combined with commercial ELISAs is an alternative to ‘gold-standard’ IP assays for the detection of DM-related autoantibodies. [ABSTRACT FROM AUTHOR]

Objective To evaluate upstream and downstream regulators leading to macrophage activation and subsequent cytokine storm in patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-associated interstitial lung disease (ILD). Methods We conducted an integrated miRNA-mRNA association analysis using circulating monocytes from 3 patients with anti-MDA5-associated ILD and 3 healthy controls and identified disease pathways and a regulator effect network by Ingenuity Pathway Analysis (IPA). The expression of relevant genes and proteins was verified using an independent validation cohort, including 6 patients with anti-MDA5-associated ILD, 5 with anti-aminoacyl tRNA synthetase antibody-associated ILD, and 6 healthy controls. Results IPA identified 26 matched pairs of downregulated miRNA and upregulated mRNAs and revealed that canonical pathways mediated by type I IFN signalling and C-C motif ligand 2 (CCL2) were responsible for the pathogenic process (P < 0.05 for all pathways). The regulatory network model identified IFN-β; Toll-like receptors 3, 7, and 9; and PU.1 as upstream regulators, while the downstream effect of this network converged at the inhibition of viral infection. mRNA and protein expression analysis using validation cohort showed a trend towards the increased expression of relevant molecules identified by IPA in patients with anti-MDA5-associated ILD compared with those with anti-aminoacyl tRNA synthetase antibody-associated ILD or healthy controls. The expression of all relevant genes in monocytes and serum levels of CCL2 and IFN-β declined after treatment in survivors with anti-MDA5-associated ILD. Conclusion An antiviral proinflammatory network orchestrated primarily by activated monocytes/macrophages might be responsible for cytokine storm in anti-MDA5-associated ILD. [ABSTRACT FROM AUTHOR]

Oishi K, Nishioka S, Okazaki Y, Hirakawa K, Nakamura M, Ichinose A, Kurihara M. Relationship between oral hygiene and function and activities of daily living at discharge in convalescent patients with stroke. Jpn J Compr Rehabil Sci 2022; 13: 17-25., Objective: This study was designed to examine the relationship between improvement in oral hygiene and function and activities of daily living (ADLs) at discharge in patients admitted to convalescent rehabilitation wards., Methods: Eligible criteria were patients with stroke with a score of 13 or higher (i.e., severe oral problems) on the Revised Oral Assessment Guide (ROAG) at admission. Age, gender, primary diseases, rehabilitation dose, dentist visits and denture status, Eichner classification, eating status at admission and discharge, and body mass index at admission were collected. The patients were classified into two groups: those with ROAG scores of less than 9 points at discharge (good ROAG group) and those with scores of 9 points or more (poor ROAG group), and Functional Independence Measure (FIM) gain and total FIM discharge scores were compared using univariate and multivariate analyses., Results: The good and poor ROAG groups comprised 126 and 366 patients, respectively. The good ROAG group had significantly higher total FIM score, FIM efficiency, and FIM gain at discharge than the poor ROAG group (112 vs. 82; P < 0.001). The ROAG scores at discharge were independently associated with FIM gain (partial regression coefficient = -9.889, 95% confidence interval = -13.499 to -6.279) and total FIM score at discharge., Conclusion: Improvement in oral hygiene and function in convalescent patients with stroke was associated with ADLs at hospital discharge., Competing Interests: Conflict of interest: There is no conflict of interest in this study., (©Kaifukuki Rehabilitation Ward Association 2022.)