Objective: Anti‐synthetase syndrome (ASSD) is a rare systemic autoimmune rheumatic disease (SARD) with significant heterogeneity and no shared classification criteria. We aimed to identify clinical and serological features associated with ASSD that may be suitable for inclusion in the data‐driven classification criteria for ASSD.Methods: We used a large, international, multicenter “Classification Criteria for Anti‐synthetase Syndrome” (CLASS) project database, which includes both patients with ASSD and controls with mimicking conditions, namely, SARDs and/or interstitial lung disease (ILD). The local diagnoses of ASSD and controls were confirmed by project team members. We employed univariable logistic regression and multivariable Ridge regression to evaluate clinical and serological features associated with an ASSD diagnosis in a randomly selected subset of the cohort.Results: Our analysis included 948 patients with ASSD and 1,077 controls. Joint, muscle, lung, skin, and cardiac involvement were more prevalent in patients with ASSD than in controls. Specific variables associated with ASSD included arthritis, diffuse myalgia, muscle weakness, muscle enzyme elevation, ILD, mechanic's hands, secondary pulmonary hypertension due to ILD, Raynaud phenomenon, and unexplained fever. In terms of serological variables, Jo‐1 and non–Jo‐1 anti‐synthetase autoantibodies, antinuclear antibodies with cytoplasmic pattern, and anti‐Ro52 autoantibodies were associated with ASSD. In contrast, isolated arthralgia, dysphagia, electromyography/magnetic resonance imaging/muscle biopsy findings suggestive of myopathy, inflammatory rashes, myocarditis, and pulmonary arterial hypertension did not differentiate between patients with ASSD and controls or were inversely associated with ASSD.Conclusion: We identified key clinical and serological variables associated with ASSD, which will help clinicians and offer insights into the development of data‐driven classification criteria for ASSD. image

Evidence related to the effectiveness of combination drug therapy for the treatment of osteoporosis is currently considered insufficient. Therefore, this study was performed to clarify the effects of monotherapy, and combination therapy, with a bisphosphonate (minodronic acid hydrate), a bone resorption inhibitor, and calcitonin (elcatonin), which is effective for the alleviation of pain due to vertebral fractures in osteoporotic patients. Study participants comprised of 51 female subjects with post-menopausal osteoporosis, whose main complaint was acute lower back pain caused by vertebral fractures. Subjects were randomly allocated into three groups and then administered with either intramuscular injections of elcatonin at a dose of 20 units weekly, minodronic acid hydrate at a dose of 1 mg daily, or a combination of these two drugs. As primary endpoints, time-dependent changes in levels of pain were assessed using a visual analog scale from baseline to 6 months of duration. In addition, we examined the effects of monotherapies, and a combination therapy on bone resorption, with changes in bone mineral density at 4 sites and advanced hip assessment parameters from baseline to 6 months. A two-tailed significance level of 5% was used for hypothesis testing. Elcatonin monotherapy showed some alleviation of pain immediately after any vertebral fractures, which was more than in the minodronic acid hydrate monotherapy group. In addition, the minodronic acid hydrate monotherapy group experienced more effective inhibited bone resorption than the elcatonin monotherapy group. In the combination therapy, the efficacy for alleviating pain and inhibiting bone resorption was equivalent to the effect observed in the elcatonin and minodronic acid hydrate monotherapy groups respectively, with further improved values of bone mineral density observed in the femoral neck and lumbar vertebrae, and in parameters of advanced hip assessment compared with both monotherapy groups. Combination therapy with elcatonin and minodronic acid hydrate appears to be an effective treatment for osteoporosis patients with lower back pain, caused by fresh vertebral fractures.

The assessment of physical function is fundamental in the management of patients with idiopathic inflammatory myopathies (IIMs). We aimed to investigate the physical function of patients with IIMs compared with those with non-IIM autoimmune rheumatic diseases (AIRDs) utilizing Patient-Reported Outcome Measurement Information System (PROMIS) Physical Function (PF) data obtained in the COVAD study, an international self-reported e-survey assessing the safety of COVID-19 vaccines in AIRDs. Demographics, AIRD diagnosis, disease activity, and PROMIS PF short form-10a data were extracted from the COVAD database. PROMIS PF-10a scores were compared between disease categories and stratified by disease activity. Factors affecting PROMIS PF-10a scores other than disease activity were identified by multivariable regression analysis in patients with inactive disease. A total of 1057 IIM patients, 3635 non-IIM AIRD patients and 3981 healthy controls (HCs) responded to the COVAD e-survey from April to August 2021. Using a binomial regression model, the predicted mean of PROMIS PF-10a scores was significantly lower in IIM patients compared with non-IIM AIRD patients or HCs [36.3 (95% CI 35.5, 37.1) vs 41.3 (95% CI 40.2, 42.5) vs 46.2 (95% CI 45.8, 46.6), P < 0.001], irrespective of disease activity. The independent factors for lower PROMIS PF-10a scores in patients with inactive disease were older age, female, longer disease duration, and a diagnosis of inclusion body myositis or polymyositis. Physical function is significantly impaired in IIMs compared with non-IIM AIRDs or HCs, even in patients with inactive disease. Our study highlights a critical need for better strategies to minimize functional disability in patients with IIMs.

An epitope is an antibody‐recognition site on a target antigen. As such, active immunization of epitope peptides may induce therapeutic efficacy equivalent to the administration of parent antibody medicines. In the present study, we designed peptides based on the epitope recognized by the tumor‐suppresive anti‐CD98 monoclonal antibody HBJ127, and investigated their efficacy for induction of antitumor immunity. The immune sera showed reactivity against the corresponding peptide–keyhole limpet hemocyanin (KLH) and peptide–bovine serum abumin (BSA) conjugates, although they did not react with CD98‐positive HeLa cells or recombinant CD98 heavy chain. To elucidate whether the epitope peptide failed to induce antitumor immunity or not, we constructed the IgG1, κ Fab phage display libraries from spleen cells of immunized mice and tried to retrieve CD98‐reactive recombinant Fab (rFab) fragments by panning against either epitope peptide–BSA conjugates or live HeLa cells. RFab fragments retrieved from peptide–BSA panning showed no reactivity to HeLa cells. Their variable‐region sequences were different from HBJ127. However, rFab fragments retrieved from HeLa cell panning showed reactivity to CD98 by indirect immunofluorescence and immunoprecipitation. Moreover, they were structurally almost identical to HBJ127. Although the immunogenicity of epitope peptides may be insufficient for induction of expected antitumor activity in vivo, we used antibody phage display to show that IgG antibodies almost identical to HBJ127 were an undetectable population in epitope peptide‐induced immune sera. (Cancer Sci 2009; 100: 126–131)

Objectives: To investigate health-related quality of life in patients with idiopathic inflammatory myopathies (IIMs) compared with those with non-IIM autoimmune rheumatic diseases (AIRDs), non-rheumatic autoimmune diseases (nrAIDs) and without autoimmune diseases (controls) using Patient-Reported Outcome Measurement Information System (PROMIS) instrument data obtained from the second COVID-19 vaccination in autoimmune disease (COVAD-2) e-survey database. Methods: Demographics, diagnosis, comorbidities, disease activity, treatments and PROMIS instrument data were analysed. Primary outcomes were PROMIS Global Physical Health (GPH) and Global Mental Health (GMH) scores. Factors affecting GPH and GMH scores in IIMs were identified using multivariable regression analysis. Results: We analysed responses from 1582 IIM, 4700 non-IIM AIRD and 545 nrAID patients and 3675 controls gathered through 23 May 2022. The median GPH scores were the lowest in IIM and non-IIM AIRD patients {13 [interquartile range (IQR) 10–15] IIMs vs 13 [11–15] non-IIM AIRDs vs 15 [13–17] nrAIDs vs 17 [15–18] controls, P < 0.001}. The median GMH scores in IIM patients were also significantly lower compared with those without autoimmune diseases [13 (IQR 10–15) IIMs vs 15 (13–17) controls, P < 0.001]. Inclusion body myositis, comorbidities, active disease and glucocorticoid use were the determinants of lower GPH scores, whereas overlap myositis, interstitial lung disease, depression, active disease, lower PROMIS Physical Function 10a and higher PROMIS Fatigue 4a scores were associated with lower GMH scores in IIM patients. Conclusion: Both physical and mental health are significantly impaired in IIM patients, particularly in those with comorbidities and increased fatigue, emphasizing the importance of patient-reported experiences and optimized multidisciplinary care to enhance well-being in people with IIMs.

Objective: Severe digital ischemia, including digital ulcers and gangrene, is considered rare in patients with antisynthetase antibodies. This study aimed to elucidate the clinical features of antisynthetase-positive patients complicated with digital ulcers and/or gangrene using a systematic literature review and case series in a single-center cohort. Methods: A systematic literature review was conducted to identify reports describing antisynthetase-positive cases with digital ulcers and/or gangrene. Our cohort of consecutive patients with antisynthetase antibodies was stratified by the history of severe digital ischemia. Demographic and clinical features and outcomes in patients with severe digital ischemia identified in the systematic literature review and our cohort were compared with those in patients without severe digital ischemia in our cohort. Results: The systematic literature review revealed 12 antisynthetase-positive patients with severe digital ischemia from one case series and eight case reports. Seven (7%) of 100 patients with antisynthetase antibodies in our cohort had a record of severe digital ischemia. Severe digital ischemia was often found at presentation and was associated with the classification of systemic sclerosis with or without myositis overlap. Clinical features associated with severe digital ischemia in antisynthetase-positive patients included Raynaud’s phenomenon ( p < 0.001), digital pitting scars ( p = 0.001), and nailfold capillary abnormality ( p = 0.02). Outcomes of severe digital ischemia were generally favorable with vasodilators. Conclusion: Severe digital ischemia is an overlooked complication in antisynthetase-positive patients. Antisynthetase antibodies should be measured in patients presenting with digital ulcers or gangrene, especially in those with systemic sclerosis phenotype and features associated with antisynthetase antibodies in the absence of systemic sclerosis-specific autoantibodies.