Data_Sheet_1_Mortality Risk Stratification Using Cluster Analysis in Patients With Myositis-Associated Interstitial Lung Disease Receiving Initial Triple-Combination Therapy.docx

ObjectiveTo stratify patients with polymyositis/dermatomyositis-associated interstitial lung disease (ILD) who were initially treated with an intensive regimen consisting of high-dose corticosteroids, a calcineurin inhibitor, and intravenous cyclophosphamide (triple-combo therapy) into subgroups based on mortality outcomes by a cluster analysis using a large-scale multicenter retrospective cohort of Japanese patients with myositis-associated ILD (JAMI).MethodsTwo-step cluster analysis of preclustering and subsequent hierarchical clustering was conducted in 185 patients who received triple-combo therapy in an unbiased manner. Initial predictors for mortality previously reported in patients with myositis-associated ILD were used as variables and included age, sex, disease duration, classification of myositis, requirement of supplemental oxygen, anti-aminoacyl tRNA synthetase (ARS) antibody, anti-melanoma differentiation-associated gene 5 (MDA5) antibody, and serum levels of C-reactive protein (CRP) and Krebs von den Lungen-6 (KL-6). The cluster model was further applied to 283 patients who received conventional regimens consisting of corticosteroids with or without a single immunosuppressive agent (dual-combo therapy or monotherapy). Cumulative survival rates were compared using Kaplan-Meier analysis, and the log-rank test was used to test for significant differences between two groups.ResultsWe developed a cluster model consisting of 6 clusters, which were categorized by age at onset, clinically amyopathic dermatomyositis, CRP, KL-6, requirement of supplemental oxygen, anti-ARS antibody, and anti-MDA5 antibody. This model was judged to be of good quality based on the silhouette measure of cohesion and separation of 0.6. These clusters were regrouped into three subsets based on low (50%) mortality rates. The performance of the clustering was generally replicated in patients who received initial dual-combo therapy or monotherapy. Survival benefits of triple-combo therapy over dual-combo therapy or monotherapy were not observed in any of the clusters.ConclusionWe successfully developed a cluster model that stratified patients with myositis-associated ILD who were treated with initial triple-combo therapy into subgroups with different prognoses, although this model failed to identify a patient subgroup that showed survival benefits from triple-combo therapy over dual-combo therapy or monotherapy.</p

sj-pdf-1-jso-10.1177_23971983221090857 – Supplemental material for Severe digital ischemia as an unrecognized manifestation in patients with antisynthetase autoantibodies: Case series and systematic literature review

Supplemental material, sj-pdf-1-jso-10.1177_23971983221090857 for Severe digital ischemia as an unrecognized manifestation in patients with antisynthetase autoantibodies: Case series and systematic literature review by Akira Yoshida, Takahisa Gono, Yuka Okazaki, Yuichiro Shirai, Mitsuhiro Takeno and Masataka Kuwana in Journal of Scleroderma and Related Disorders</p

Data_Sheet_1_Tertiary lymphoid structures in the primary tumor site of patients with cancer-associated myositis: A case–control study.docx

ObjectiveTo investigate histologic features of immunological components in the primary tumor site of patients with cancer-associated myositis (CAM) by focusing on tumor-infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLSs), which play major roles in antitumor immunity.MethodsCancer-associated myositis patients were selected from the single-center idiopathic inflammatory myopathy cohort based on the availability of primary tumor specimens obtained before the introduction of immunomodulatory agents. Control cancer subjects without CAM were selected from the cancer tissue repository at a ratio of 1:2 matched for demographics and cancer characteristics of CAM cases. A series of immunohistochemical analyses was conducted using sequential tumor sections. TLS was defined as an ectopic lymphoid-like structure composed of DC-LAMP+ mature dendritic cells, CD23+ follicular dendritic cells (FDCs) and PNAd+ high endothelial venules. TLS distribution was classified into the tumor center, invasive margin, and peritumoral area.ResultsSix CAM patients and 12 matched non-CAM controls were eligible for the study. There was no apparent difference in the density or distribution of TILs between the groups. TLSs were found in 3 CAM patients (50%) and 4 non-CAM controls (33%). TLSs were exclusively located at the tumor center or invasive margin in CAM cases but were mainly found in the peritumoral area in non-CAM controls. FDCs and class-switched B cells colocalized with follicular helper T cells were abundantly found in the germinal center-like area of TLSs from CAM patients compared with those from non-CAM controls.ConclusionThe adaptive immune response within TLSs in the primary tumor site might contribute to the pathogenic process of CAM.</p

A cumulative effect of risk allele number (<i>C8orf13–BLK</i> rs13277113A and <i>STAT4</i> rs7574865T) on susceptibility to polymyositis, dermatomyositis, and polymyositis/dermatomyositis.

<p>OR: Odds ratio, CI: confidence interval, PM: polymyositis, DM: dermatomyositis, N.S.: not significant.</p

Association between <i>C8orf13–BLK</i> rs13277113 and polymyositis/dermatomyositis.

<p>OR: Odds ratio, CI: confidence interval, PM: polymyositis, DM: dermatomyositis, N.S.: not significant.</p