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This article discusses a case report of a 64-year-old woman with dermatomyositis (DM) who had both anti-MDA5 and anti-Ro52 antibodies. The patient experienced skin manifestations, joint pain, fatigue, and difficulty breathing. Blood tests and imaging confirmed lung and muscle involvement. Early detection of the co-positive anti-Ro52 antibody allowed for aggressive treatment and a positive outcome. The article highlights the significance of a thorough autoimmune evaluation in understanding the disease and making informed treatment decisions. The document also presents a unique case of DM that was positive for anti-MDA5 antibody but presented with myositis symptoms and imaging findings. The patient received a combination therapy that improved their oxygenation and skin symptoms. The document stresses the importance of early treatment initiation and comprehensive evaluation of autoantibodies for predicting prognosis and selecting appropriate treatment. [Extracted from the article]

Interstitial lung disease is a common complication of anti-synthetase syndrome (ASS), and lymphocytic infiltration is often observed in the lesion. We have recently reported that disease-specific autoantibodies are produced by infiltrating lymphocytes in some autoimmune diseases. Here, we investigate the antigen specificity of B cells in the lung lesions of ASS patients. A total of 177 antibodies were produced from antibody-secreting cells in bronchoalveolar fluid (BALF) of three each of serum anti-Jo-1 and serum anti-EJ antibody-positive patients. Twelve to 30% and 50 to 62% of these antibodies were diseasespecific autoantibodies, respectively. These autoantibodies recognized conformational epitopes of the whole self-antigen and had affinity maturations, indicating that self-antigens themselves are the target of humoral immunity. In addition, 100 antibodies were produced from two salivary gland tissues, obtained by chance, of ASS patients. Salivary glands are not generally recognized as lesions of ASS, but unexpectedly, ASS-related autoantibody production was also observed similar to that of BALF. Immunostaining confirmed the presence of ASS-related autoantibody-producing cells in salivary glands. Our results suggest that disease-specific autoantibody production at lesion sites is a common pathogenesis of autoimmune diseases, and that tissue-specific production of autoantibodies can provide insights regarding the distribution of organ manifestations in autoimmune diseases. [ABSTRACT FROM AUTHOR]

This article discusses a case of a 10-year-old girl who was diagnosed with juvenile dermatomyositis (JDM), a rare autoimmune disorder. The patient presented with symptoms such as joint pain, edema, and skin rash. The diagnosis was confirmed through physical examination, laboratory tests, and imaging. The patient's condition worsened and she developed complications including interstitial lung disease (ILD) and macrophage activation syndrome (MAS). Despite treatment with various medications and therapies, the patient's condition deteriorated and she ultimately died due to multiple organ failure. The article highlights the challenges in diagnosing and treating JDM, particularly in cases with complications. The authors suggest that more intensive therapy and the use of immune regulators may be necessary for better outcomes in these cases. [Extracted from the article]

Abstract Protein tripartite motif-containing 21 (TRIM21/Ro52), an E3 ubiquitin ligase, is an essential regulator of innate immunity, and its dysregulation is closely associated with the development of autoimmune diseases, predominantly systemic lupus erythematosus (SLE) and primary Sjögren’s syndrome (pSS). TRIM21 /Ro52 also features anti-cancer and carcinogenic functions according to different malignancies. The interconnected role of TRIM21/Ro52 in regulating autoimmunity and cell metabolism in autoimmune diseases and malignancies is implicated. In this review, we summarize current findings on how TRIM21/Ro52 affects inflammation and tumorigenesis, and investigate the relationship between TRIM21/Ro52 expression and the formation of lymphoma and breast cancer in SLE and pSS populations.

Abstract Background This study aimed to describe the clinical characteristics and analyze the poor prognostic factors in patients with anti-MDA5 dermatomyositis. Methods A total of 126 adults with anti-MDA5 dermatomyositis were enrolled in this retrospective study. Information on survival time, cause of death, and baseline characteristics was collected. Patients were divided into two groups: a survival group and a non-survival group. Items with clinical significance that showed significant differences between the two groups were screened by Kaplan–Meier and Cox regression analyses to identify the predictors of poor survival. Results Thirty-two patients were included in the non-survival group, most of whom died from respiratory failure, with pulmonary infection accounting for half. Epstein–Barr virus infection was relatively common in both groups. Aspartate transaminase, lactate dehydrogenase, and ferritin levels; erythrocyte sedimentation rate; and anti-Ro52 antibody levels were significantly higher, while the lymphocyte count was lower in the non-survival group compared with the survival group. Notably, patients in the non-survival group were more likely to present with rapidly progressive interstitial lung disease than those in the survival group. Kaplan–Meier and Cox multivariate regression analyses revealed that the prevalence of rapidly progressive interstitial lung disease, levels of anti-Ro52 antibody, and age > 57 years were important prognostic factors independent of multiple clinical parameters. Conclusions Rapidly progressive interstitial lung disease, anti-Ro52 antibody levels, and age > 57 years are possible predictors of mortality risk in patients with anti-MDA5 dermatomyositis.

Protein tripartite motif-containing 21 (TRIM21/Ro52), an E3 ubiquitin ligase, is an essential regulator of innate immunity, and its dysregulation is closely associated with the development of autoimmune diseases, predominantly systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS). TRIM21 /Ro52 also features anti-cancer and carcinogenic functions according to different malignancies. The interconnected role of TRIM21/Ro52 in regulating autoimmunity and cell metabolism in autoimmune diseases and malignancies is implicated. In this review, we summarize current findings on how TRIM21/Ro52 affects inflammation and tumorigenesis, and investigate the relationship between TRIM21/Ro52 expression and the formation of lymphoma and breast cancer in SLE and pSS populations. [ABSTRACT FROM AUTHOR]

To analyze the clinical characteristics and risk factors of the patients with primary Sjogren’s syndrome (pSS) complicated with interstitial lung disease (ILD), and to improve the clinicians’understandings of the disease, and to provide the evidence for the early detection of extradular organ involvement by the clinicians. Methods The clinical characteristics of 176 patients with pSS were collected and were divided into pSS complicated with ILD group (n=21) and pSS complicated without ILD group (n=155) according to whether the patients were complicated with ILD.The levels of hemoglobin (Hb), white blood cells (WBC), platelets (PLT), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)，rheumatoid factor (RF)，immunoglobulin G (IgG)，immunoglobulin M (IgM)，immunoglobulin A (IgA), complement 3 (C3), complement 4 (C4), and the positive rates of granular type antinuclear antibodies, cytoplasmic granular type antinuclear antibodies, homogeneous type antinuclear antibodies, anti-SSA, anti-SSB, and anti-Ro-52 antibodies of the patients in two groups were compared.Univariate and multivariate Logistic regression analysis were used to analyze the clinical characteristics and laboratory indexes of the pSS patients complicated with ILD. Results Among the 176 pSS patients, the ratio of male to female was 1∶28, with the median age of 49 (39－58) years and the median course of 24 (24－48) months. Compared with pSS complicated without ILD group，the age of the patients in ILD group was older (P<0.01), and the level of ESR was increased(P<0.01)，the positive rates of cytoplasmic granular type antinuclear antibody and anti-Ro-52 antibody were increased (P<0.01). The multivariate Logistic regression analysis results showed that the increasing of ESR level (OR=1.046，95% CI： 1.026－1.066, P=0.001) and positive granulosa type (OR=4.676，95% CI： 1.156－18.916, P=0.031) were the risk factors for ILD complicated with pSS. Conclusion The patients with pSS complicated by ILD have an older onset age and higher ESR levels； ILD is more likely to occur when the cytoplasmic granular type antinuclear antibody and anti-Ro-52 antibody of the patients are positive； the increasing of the ESR level and positive coated granular type antinuclear antibody are the risk factors for the pSS complicated with ILD. [ABSTRACT FROM AUTHOR]

Anti‐MDA5 antibody dermatomyositis (DM) is a special type of myositis, which can potentially cause rapidly progressive interstitial lung disease (RP‐ILD). Mixed connective tissue disease (MCTD) is a complex disease with different characteristics of autoimmune connective tissue disease, associated with ILD. Both are rare diseases, and few patients with both diseases have been reported. A 71‐year‐old woman complained of palpitations, with a 2 months history of rash around her hands, extensor surface of right elbow, and the nape of her neck. Subsequently, the patient had acute exacerbation of dyspnea and tachypnea. Anti‐Ro52, U1 RNP and MDA5 antibodies were positive; the presenting evidence was suggestive of anti‐MDA5+DM‐RP‐ILD complicated with MCTD. Our patient deteriorated rapidly and had a fatal outcome, despite "triple therapy" for RP‐ILD. This case illustrates that patients with coexisting anti‐MDA5+DM and MCTD have the former's typical clinical manifestations, and may develop ILD quickly rather than slowly as in MCTD, especially with the coexistence of anti‐Ro52 antibodies. [ABSTRACT FROM AUTHOR]

Background: Pulmonary fibrosis is common in primary Sjögren's syndrome (pSS)-related interstitial lung disease (ILD). However, research is lacking on the diagnostic immunological examination of pSS-related pulmonary fibrosis. Particularly, the value of detecting anti-Ro52 antibody in pulmonary fibrosis is unclear. Objective: To evaluate the potential diagnostic value of anti-SSA, anti-SSB, and anti-Ro52 autoantibodies as markers of pSS-related pulmonary fibrosis. Methods: One-hundred seventy-nine patients with pSS were analyzed retrospectively at our hospital. They were divided into the fibrosis and non-fibrosis groups. Pulmonary fibrosis was classified as mild, moderate, or severe based on the patients' computed tomography (CT) findings. Laboratory examinations, including anti-SSA, anti-SSB, and anti-Ro52 antibody evaluations, were performed. The influencing factors of pulmonary fibrosis were analyzed using logistic regression. Results: Chest CT revealed pulmonary fibrosis in 45 patients with pSS (25.1%). The positive rates of anti-SSA and anti-Ro52 antibodies in the fibrosis group were lower than in the non-fibrosis group (P=0.04, P=0.001). The frequency of anti-Ro52 antibody showed no significant differences between mild-to-moderate (53.8%) and severe (47.3%) pulmonary fibrosis. The anti-Ro52 antibody was identified as a potentially protective factor against pSS (P=0.041). Conclusions: Patients with pSS and pulmonary fibrosis had a low frequency of anti-SSA and anti-Ro52 antibodies. In patients with pSS and negative anti-Ro52 antibody, a chest CT is recommended to further understand the patients' condition.

Abstract A 65‐year‐old female was admitted with rapidly progressive respiratory failure requiring intubation and mechanical ventilation. She was considered to have an infective exacerbation of underlying interstitial lung disease (ILD). She improved on antibiotics, but the interstitial process progressed rapidly, and she could not be weaned. An antimyositis antibody panel yielded a strongly positive anti‐Jo‐1 and anti‐Ro 52. A diagnosis of antisynthetase syndrome (ASS) associated ILD, a very rare disease with high mortality, was made. She was managed with high‐dose corticosteroids and intravenous immunoglobulin therapy and was eventually liberated from mechanical ventilation. This case highlights the importance of considering ASS in an otherwise unexplained rapidly progressive ILD requiring mechanical ventilation.

Objectives In the present study, we aimed to assess the prevalence and clinical significance of anti-Ro52 antibodies in a cohort of patients with idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD) with different myositis-specific autoantibodies (MSAs). Methods A cohort of 267 IIM-ILD patients, including 62 patients with PM, 126 patients with DM and 79 patients with clinically amyopathic DM (CADM) were retrospectively analysed in this study. Clinical and laboratory findings, pulmonary function tests (PFTs), HRCT patterns and treatment information were compared between patients with and without anti-Ro52 antibodies. The association between prognosis and anti-Ro52 antibodies was also evaluated based on different MSA subgroups. Results Anti-Ro52 antibodies were more frequent in patients with anti-MDA5 (62.1%, P  < 0.01) and anti-Jo1 (64.9%, P  < 0.01) antibodies than in those with other MSAs. The proportion of patients with anti-Jo1 antibodies was higher in the anti-Ro52 antibody-positive group than in the anti-Ro52 antibody-negative group. Patients with anti-Ro52 antibodies were more likely to exhibit the Gottron sign than the anti-Ro52 antibody-negative group (P  < 0.001). Furthermore, it was a predictive factor for rapid progression interstitial lung disease (RP-ILD) (P  = 0.001) and was also associated with a higher mortality rate (log-rank test, P  = 0.001). Furthermore, RP-ILD was more frequently exhibited in anti-MDA5- and anti-Ro52-positive patients. Moreover, anti-Ro52 antibody positivity was closely associated with a higher mortality rate in anti-MDA5-ILD patients (log-rank test, P  < 0.05). Conclusions Anti-Ro52 antibodies were highly prevalent in patients with anti-MDA5 and anti-Jo1 antibodies. Within all patients with IIM-ILD, those with anti-Ro52 autoantibodies had a higher frequency of RP-ILD and a poorer prognosis, especially in the anti-MDA5 antibody subgroup. [ABSTRACT FROM AUTHOR]

Background: Anti-melanoma differentiation-associated gene 5 antibodypositive dermatomyositis with interstitial lung disease (anti-MDA5 DM-ILD) is a disease with high mortality. We sought to develop an effective and convenient prediction tool to estimate mortality risk in patients with anti-MDA5 DM-ILD and inform clinical decision-making early. Methods: This prognostic study included Asian patients with anti-MDA5 DM-ILD hospitalized at the Nanjing Drum Hospital from December 2016 to December 2020. Candidate laboratory indicators were retrospectively collected. Patients hospitalized from2016 to 2018 were used as the discovery cohort and applied to identify the optimal predictive features using a least absolute shrinkage and selection operator (LASSO) logistic regression model. A risk score was determined based on these features and used to construct the mortality risk prediction model in combination with clinical characteristics. Results were verified in a temporal validation comprising patients treated between 2019 and 2020. The primary outcome was mortality risk within one year. The secondary outcome was overall survival. The predictionmodel's performance was assessed in terms of discrimination, calibration, and clinical usefulness. Results: This study included 127 patients, (72 men [56.7%]; median age, 54 years [interquartile range, 48-63 years], split into discovery (n = 87, 70%) and temporal validation (n=37, 30%) cohorts. Five optimal features were selected by LASSO logistic regression in the discovery cohort (n = 87) and used to construct a risk score, including lymphocyte counts, CD3+CD4+ T-cell counts, cytokeratin 19 fragment (CYFRA21-1), oxygenation index, and anti-Ro52 antibody. The retained predictive variables in the final prediction model were age, Heliotrope, fever, and risk score, and the most predictive factor was the risk score. The prediction model showed good discrimination (AUC: 0.915, 95% CI: 0.846-0.957), good calibration (Hosmer-Lemeshow test, P = 0.506; Brier score, 0.12), and fair clinical usefulness in the discovery cohort. The results were verified among patients in the temporal validation cohort (n = 38). We successfully divided patients into three risk groups with very different mortality rates according to the predictive score in both the discovery and validation cohorts (Cochran-Armitage test for trend, P < 0.001). Conclusions: We developed and validated a mortality risk prediction tool with good discrimination and calibration for Asian patients with anti-MDA5 DM-ILD. This tool can offer individualized mortality risk estimation and inform clinical decision-making. [ABSTRACT FROM AUTHOR]

Sicca syndrome, which is typical for Sjögren’s syndrome (SS), is relatively often comorbid with other autoimmune diseases. The current classification criteria for SS published in 2016 include only anti-SSA (anti-Ro) autoantibody, while the latest literature proposes that anti-Ro60/anti-Ro52 autoantibody profiles should be used instead, as these two types of antibodies correlate with specific clinical symptoms and laboratory test findings. The paper presents the case of a 41-year-old woman suffering from primary Sjögren’s syndrome (pSS) and her three daughters, who were under observation for rheumatic disorders due to sicca symptoms, especially pSS, as well as a discussion on separate determination of anti-Ro60 and anti-Ro52 autoantibodies based on current literature in the PubMed database. When testing with antinuclear antibodies, the Ro60+Ro52+La+ autoantibody profile most closely matches for pSS. Further research is needed to find marker antibodies for SS and quantification methods.

A 65‐year‐old female was admitted with rapidly progressive respiratory failure requiring intubation and mechanical ventilation. She was considered to have an infective exacerbation of underlying interstitial lung disease (ILD). She improved on antibiotics, but the interstitial process progressed rapidly, and she could not be weaned. An antimyositis antibody panel yielded a strongly positive anti‐Jo‐1 and anti‐Ro 52. A diagnosis of antisynthetase syndrome (ASS) associated ILD, a very rare disease with high mortality, was made. She was managed with high‐dose corticosteroids and intravenous immunoglobulin therapy and was eventually liberated from mechanical ventilation. This case highlights the importance of considering ASS in an otherwise unexplained rapidly progressive ILD requiring mechanical ventilation. [ABSTRACT FROM AUTHOR]

Background: Programmed cell death protein-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors therapy is now a routine scheme in cancers. However, the effect of preexisting autoantibodies on the safety and efficacy of PD-1/PD-L1 inhibitors in cancer patients is not well understood. Methods: The present retrospective cohort study evaluated the safety and efficacy of PD-1/PD-L1 inhibitors in patients with preexisting autoantibodies. Patients who received PD-1/PD-L1 inhibitors in the Department of Medical Oncology, Peking Union Medical College Hospital between November 2017 and August 2021 were reviewed. Results: 67 (37.9%) of the 177 patients, 27 (20.3%) of the 133 patients, and 16 (11.0%) of 146 patients who received PD-1/PD-L1 inhibitors were positive for ANA, anti-Ro52, and antithyroid antibodies, respectively. Preexisting ANA and anti-Ro52 antibody were not associated with the increased risk of immune-related adverse events (irAEs), while thyroid dysfunction was more frequent in patients with positive antithyroid antibody (75.0% versus 13.8%, p < 0.001). The median progression-free survival (PFS, 13.1 versus 7.0 months, p = 0.015) was significantly longer in the ANA-positive patients, while the median overall survival (OS, 14.5 versus 21.8 months, p = 0.67) did not differ significantly between the ANA-positive and ANA-negative groups. Moreover, the preexisting anti-Ro52 and antithyroid antibodies were not significantly associated with PFS and OS. Conclusions: The presence of ANA and anti-Ro52 antibody were not associated with a higher risk of irAEs, whereas patients positive for antithyroid antibody should monitor closely immune-related thyroid dysfunction. Preexisting ANA might be a predictor of longer PFS, while anti-Ro52 and antithyroid antibodies had no significant effect on survival outcomes in patients receiving PD-1/PD-L1 inhibitors therapy. [ABSTRACT FROM AUTHOR]

BackgroundProgrammed cell death protein-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors therapy is now a routine scheme in cancers. However, the effect of preexisting autoantibodies on the safety and efficacy of PD-1/PD-L1 inhibitors in cancer patients is not well understood.MethodsThe present retrospective cohort study evaluated the safety and efficacy of PD-1/PD-L1 inhibitors in patients with preexisting autoantibodies. Patients who received PD-1/PD-L1 inhibitors in the Department of Medical Oncology, Peking Union Medical College Hospital between November 2017 and August 2021 were reviewed.Results67 (37.9%) of the 177 patients, 27 (20.3%) of the 133 patients, and 16 (11.0%) of 146 patients who received PD-1/PD-L1 inhibitors were positive for ANA, anti-Ro52, and antithyroid antibodies, respectively. Preexisting ANA and anti-Ro52 antibody were not associated with the increased risk of immune-related adverse events (irAEs), while thyroid dysfunction was more frequent in patients with positive antithyroid antibody (75.0% versus 13.8%, p < 0.001). The median progression-free survival (PFS, 13.1 versus 7.0 months, p = 0.015) was significantly longer in the ANA-positive patients, while the median overall survival (OS, 14.5 versus 21.8 months, p = 0.67) did not differ significantly between the ANA-positive and ANA-negative groups. Moreover, the preexisting anti-Ro52 and antithyroid antibodies were not significantly associated with PFS and OS.ConclusionsThe presence of ANA and anti-Ro52 antibody were not associated with a higher risk of irAEs, whereas patients positive for antithyroid antibody should monitor closely immune-related thyroid dysfunction. Preexisting ANA might be a predictor of longer PFS, while anti-Ro52 and antithyroid antibodies had no significant effect on survival outcomes in patients receiving PD-1/PD-L1 inhibitors therapy.

Abstract Background Coronavirus disease 2019 (COVID-19) has reach pandemic proportions globally. For patients with symptoms of fever and cough accompanied by rapid lung damage progression, COVID-19 needs to be distinguished from interstitial lung disease (ILD) attributed to connective tissue disease (CTD), especially dermatomyositis (DM)/clinical amyopathic dermatomyositis (CADM) associated rapidly progressive interstitial lung disease (RP-ILD). Case presentation We report a case of a woman observed with fever, cough, and rapid lung damage during the epidemic. The patient had a suspicious epidemiological history, and her chest CT scans showed lung damage similar to that caused by COVID-19, but anti-Ro52 antibody was strongly positive. She was diagnosed with CADM associated RP-ILD and died 1 month later. Conclusions During the COVID-19 epidemic, it is critical to carefully assess patients with CTD related ILD, especially RP-ILD associated with CADM. Repeated nucleic acid tests for COVID-19 are necessary to achieve accurate case diagnosis. High-resolution CT (HRCT) of the chest is presently deemed an inefficient technique to distinguishing between COVID-19 and CADM associated RP-ILD. The characteristic rashes of dermatomyositis require careful observation and can often provide diagnostic clues. For patients with CADM, a high titers of anti-Ro52 antibody may be related to the pathogenesis of RP-ILD, suggesting a poor prognosis.

This case report highlights dermatomyositis (DM) characterised by the concurrent presence of anti-melanoma differentiation-associated protein 5 (anti-MDA5) and anti-Ro52 antibodies. A 64-year-old woman initially presented with erythema on the palms, which later spread to the dorsum of the hands, followed by involvement of the face, forehead, and upper eyelids. The patient reported joint pain, fatigue, and dyspnea. Physical examination revealed characteristic cutaneous manifestations, including heliotrope rash and Gottron's sign, accompanied by skin ulceration and muscle weakness. Blood tests showed elevated levels of creatine phosphokinase and C-reactive protein. A high-resolution computed tomography (HRCT) scan revealed interstitial lung disease (ILD) with an organising pneumonia (OP) pattern. Magnetic resonance imaging (MRI) confirmed the presence of myositis. Autoantibody analysis revealed concurrent positivity for both anti-MDA5 and anti-Ro52 antibodies. At the time of diagnosis, she had no respiratory impairment, but had an elevated C-reactive protein and high levels of anti-MDA5 antibody. She was started on triple combination therapy with glucocorticoids, cyclophosphamide, and tacrolimus. She had worsening oxygenation and elevated ferritin during the first weeks of treatment, but then her symptoms improved. Early detection of a co-positive anti-Ro52 antibody led to early initiation of triple combination therapy and a good prognosis., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

Interstitial lung disease is a common complication of anti-synthetase syndrome (ASS), and lymphocytic infiltration is often observed in the lesion. We have recently reported that disease-specific autoantibodies are produced by infiltrating lymphocytes in some autoimmune diseases. Here, we investigate the antigen specificity of B cells in the lung lesions of ASS patients. A total of 177 antibodies were produced from antibody-secreting cells in bronchoalveolar fluid (BALF) of three each of serum anti-Jo-1 and serum anti-EJ antibody-positive patients. Twelve to 30% and 50 to 62% of these antibodies were disease-specific autoantibodies, respectively. These autoantibodies recognized conformational epitopes of the whole self-antigen and had affinity maturations, indicating that self-antigens themselves are the target of humoral immunity. In addition, 100 antibodies were produced from two salivary gland tissues, obtained by chance, of ASS patients. Salivary glands are not generally recognized as lesions of ASS, but unexpectedly, ASS-related autoantibody production was also observed similar to that of BALF. Immunostaining confirmed the presence of ASS-related autoantibody-producing cells in salivary glands. Our results suggest that disease-specific autoantibody production at lesion sites is a common pathogenesis of autoimmune diseases, and that tissue-specific production of autoantibodies can provide insights regarding the distribution of organ manifestations in autoimmune diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Takeshita, Suzuki, Nakazawa, Kamata, Ishii, Oyamada, Oshima, Usuda, Tsunoda and Takeuchi.)

Objective Anti-Ro52 antibody often co-occurs with anti-Jo1 antibody in antisynthetase syndrome and their co-occurrence correlates with a more aggressive clinical phenotype and poorer prognosis. The strong association of anti-Ro52 antibody with anti-melanoma differentiation-associated protein-5 (anti-MDA5) antibody has been indicated in juvenile myositis. The aim of this study was to assess the clinical significance of anti-Ro52 antibody in a cohort of adult patients with anti-MDA5-positive clinically amyopathic dermatomyositis with interstitial lung disease (CADM-ILD). Methods We assessed a cohort of 83 consecutive patients with anti-MDA5-positive CADM-ILD. Anti-MDA5 antibodies and anti-Ro52 antibodies were detected in immunoblotting and semi-quantitatively analysed by densitometry. Clinical features and the 24 month survival were compared between anti-MDA5-positive patients with and without anti-Ro52 antibodies. Results Anti-Ro52 antibodies were found in 74.7% of anti-MDA5-positive CADM-ILD patients and were associated with an increased frequency of rapidly progressive interstitial lung disease (RP-ILD; 54.8% vs 23.8%; P  = 0.014) and cutaneous ulcerations (27.4% vs 4.8%; P  = 0.033). The cumulative 24 month survival rate tended to be lower in patients with anti-Ro52 antibodies than patients without (59.9% vs 85.7%; P  = 0.051). The combination of anti-Ro52 antibody status and anti-MDA5 antibody levels further stratified patients' survival rates, showing that the survival rate of patients who were dual positive for anti-MDA5 antibody and anti-Ro52 antibody was significantly lower than patients with mild positive anti-MDA5 antibody alone (59.9% vs 100%; P  = 0.019). Conclusion Anti-Ro52 antibody is highly prevalent in anti-MDA5-positive CADM-ILD patients and their coexistence correlates with a subgroup of patients with more aggressive phenotypes. The combination of anti-MDA5 antibody levels and anti-Ro52 antibody status could help to predict patients' prognosis and guide risk-based therapy. [ABSTRACT FROM AUTHOR]

Sicca syndrome, which is typical for Sjögren's syndrome (SS), both primary (pSS) and secondary (sSS), is relatively often comorbid with other autoimmune diseases. The current classification criteria for SS published in 2016 include only anti-SSA (anti-Ro) autoantibody, while the latest literature proposes that anti-Ro60/anti-Ro52 autoantibody profiles should be used instead, as these two types of antibodies correlate with specific clinical symptoms and laboratory test findings. The paper presents the case of a 41-year-old woman suffering from pSS and her three daughters, who were under observation for rheumatic disorders due to sicca symptoms, especially pSS, as well as a discussion on separate determination of anti-Ro60 and anti-Ro52 autoantibodies based on current literature in the PubMed database. When testing with antinuclear antibodies, the Ro60+Ro52+La+ autoantibody profile most closely matches for pSS. Further research is needed to find marker antibodies for SS and quantification methods. [ABSTRACT FROM AUTHOR]

Objectives: To clarify clinical features of anti-Ro52 antibody (Ab)-positive polymyositis (PM)/dermatomyositis (DM)., Patients and Methods: We retrospectively examined clinical features and status of anti-Ro52 Ab in patients with PM/DM admitted at the University of Tsukuba Hospital between January 2019 and February 2023. We compared anti-Ro52 Ab-positive and -negative groups., Results: A total of 40 patients were selected and analyzed. Median age at diagnosis was 61.5 (48.8-69.3) years and 34 cases were female. Twenty-three cases were PM and 17 cases were DM (including 6 clinically amyopathic dermatomyositis: CADM). Twenty-two cases were positive for anti-Ro52 Ab, 14 for anti-ARS Ab, and 6 for anti-MDA5 Ab. Interstitial lung disease (ILD) was detected in 29 cases, 9 of which were rapidly progressive. Glucocorticoid (GC)-resistant cardiomyopathy was detected in 6 cases, malignancy in 3 cases, and Sjögren's syndrome (SS) in 4 cases. Of the 22 anti-Ro52 Ab positive cases, only 3 were single-positive and the remaining 19 cases simultaneously had other autoantibodies. Comparing the anti-Ro52 Ab-positive and -negative groups, the frequencies of anti-ARS Ab positivity (63.6% vs. 0%), ILD (95.5% vs. 44.4%), GC-resistant cardiomyopathy (27.3% vs. 0%), concomitant use of immunosuppressants (95.5% vs. 55.6%), and levels of C-reactive protein (CRP) were significantly higher in the anti-Ro52 Ab-positive group (p<0.05). The frequencies of PM/DM, positivity of anti-MDA5 Ab, malignancies, and SS were comparable between groups., Conclusion: Anti-Ro52 Ab were frequently positive in PM/DM and anti-Ro52 Ab-positive patients showed significantly higher rates of anti-ARS Ab positivity and ILD, GC-resistant cardiomyopathy, concomitant use of immunosuppressants, and higher levels of CRP. Anti-Ro52 Ab may be useful as a severity marker in PM/DM., (© Japan College of Rheumatology 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

• High mortality of coexistence of ILD in patients with IIM. • Patients with interstitial lung disease had lower initial creatine kinase levels. • Patients with anti-Ro52 antibodies had 9.17-fold increased odds of ILD. • Patients with anti-Ro52 or anti-Jo1 antibodies had 13.44-fold increased odds of ILD. • The common serology tests can guide pulmonary screening for patients with IIM. Interstitial lung disease (ILD) is an extramuscular manifestation associated with increased mortality in idiopathic inflammatory myopathy (IIM). To identify risk factors for ILD in patients with IIM, this study retrospectively enrolled 117 eligible patients from a university medical center. After a comprehensive chart review, 56 patients were stratified into ILD (n = 28) and non-ILD (n = 28) groups. Clinical features, laboratory data, concomitant diseases, and serology profiles were compared. Patients with ILD had high prevalence of anti-Jo1 antibodies (p = 0.002), anti-Ro52 antibodies (p < 0.001), both anti-Jo1 and anti-Ro52 antibodies (p = 0.008), anti-Jo1 or anti-Ro52 antibodies (p < 0.001), and lower initial creatine kinase (CK) levels (p = 0.006). Moreover, patients with anti-Ro52 antibodies and either anti-Ro52 or anti-Jo1 antibodies had 9.17-fold (95% confidence interval [CI]: 2.858–33.487, p < 0.001) and 13.44-fold (95% CI: 4.008–52.757, p < 0.001) increased odds of developing ILD, respectively. By contrast, patients with higher CK levels had 0.99-fold (95% CI: 0.999–0.999, p = 0.011) increased odds of developing ILD. Both anti-Ro52 and anti-Jo1 antibodies were independent serological risk factors for IIM-associated ILD. Because these serology tests are commonly available, they can be used to guide pulmonary screening for patients with IIM to increase neurologist proactivity in recognizing and treating extramuscular conditions. [ABSTRACT FROM AUTHOR]

Aims The human ether-a-go-go- related gene (hERG) encodes the rapidly activating delayed rectifier potassium channel (IKr). Malfunction of hERG/IKr is the primary cause of acquired long QT syndrome (LQTS), an electrical disorder of the heart that can cause arrhythmias and sudden death. Patients with autoimmune diseases display a high incidence of LQTS. While dysfunction of hERG channels induced by autoantibodies such as anti-Ro52 may play a role in this pathology, the underlying mechanisms are not well understood. Here, we investigated the acute and chronic effects of anti-Ro52 antibody on hERG channels stably expressed in human embryonic kidney (hERG-HEK) 293 cells as well as IKr in neonatal rat ventricular myocytes. Methods and results Using whole-cell patch clamp, western blot analyses, and immunocytochemistry, we found that a 12-h treatment of hERG-HEK cells with patients' sera containing anti-Ro52 autoantibody decreased the hERG current (IhERG) by 32% compared to cells treated with autoantibody-negative patients' sera. Commercial anti-Ro52 antibody at 100 µg/mL did not acutely block IhERG. Instead, a 12-h treatment with anti-Ro52 antibody at a concentration of 4 µg/mL significantly reduced mature hERG protein expression and IhERG. Specifically, anti-Ro52 antibody did not acutely block hERG current but chronically facilitated hERG endocytic degradation. The extracellular S5-pore linker of hERG, which forms the turret of the channel on the outside of the cell, is the target region for anti-Ro52-mediated hERG reduction since its replacement with the analogous region of EAG abolished the anti-Ro52 effect. In neonatal rat ventricular myocytes, 100 µg/mL anti-Ro52 antibody did not acutely block IKr, but a 12-h treatment of cells with 4 µg/mL anti-Ro52 antibody selectively reduced IKr and prolonged the action potential duration. Conclusions Our results indicate that anti-Ro52 antibody acts on the hERG S5-pore linker to chronically decrease hERG expression and current. These findings provide novel insights into hERG regulation and anti-Ro52 antibody-associated LQTS. [ABSTRACT FROM AUTHOR]

Background: Anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis with interstitial lung disease (anti-MDA5 DM-ILD) is a disease with high mortality. We sought to develop an effective and convenient prediction tool to estimate mortality risk in patients with anti-MDA5 DM-ILD and inform clinical decision-making early., Methods: This prognostic study included Asian patients with anti-MDA5 DM-ILD hospitalized at the Nanjing Drum Hospital from December 2016 to December 2020. Candidate laboratory indicators were retrospectively collected. Patients hospitalized from 2016 to 2018 were used as the discovery cohort and applied to identify the optimal predictive features using a least absolute shrinkage and selection operator (LASSO) logistic regression model. A risk score was determined based on these features and used to construct the mortality risk prediction model in combination with clinical characteristics. Results were verified in a temporal validation comprising patients treated between 2019 and 2020. The primary outcome was mortality risk within one year. The secondary outcome was overall survival. The prediction model's performance was assessed in terms of discrimination, calibration, and clinical usefulness., Results: This study included 127 patients, (72 men [56.7%]; median age, 54 years [interquartile range, 48-63 years], split into discovery (n = 87, 70%) and temporal validation (n=37, 30%) cohorts. Five optimal features were selected by LASSO logistic regression in the discovery cohort (n = 87) and used to construct a risk score, including lymphocyte counts, CD3+CD4+ T-cell counts, cytokeratin 19 fragment (CYFRA21-1), oxygenation index, and anti-Ro52 antibody. The retained predictive variables in the final prediction model were age, Heliotrope, fever, and risk score, and the most predictive factor was the risk score. The prediction model showed good discrimination (AUC: 0.915, 95% CI: 0.846-0.957), good calibration (Hosmer-Lemeshow test, P = 0.506; Brier score, 0.12), and fair clinical usefulness in the discovery cohort. The results were verified among patients in the temporal validation cohort (n = 38). We successfully divided patients into three risk groups with very different mortality rates according to the predictive score in both the discovery and validation cohorts (Cochran-Armitage test for trend, P < 0.001)., Conclusions: We developed and validated a mortality risk prediction tool with good discrimination and calibration for Asian patients with anti-MDA5 DM-ILD. This tool can offer individualized mortality risk estimation and inform clinical decision-making., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gui, Li, Yu, Zhao, Jin, Meng, Wang, Shi, Yu, Ma, Chen, Luan, Xin, Qiu, Qiu, Zhang, Cao, Cao, Dai, Cai, Huang and Xiao.)

Background: Pulmonary fibrosis is common in primary Sjögren's syndrome (pSS)-related interstitial lung disease (ILD). However, research is lacking on the diagnostic immunological examination of pSS-related pulmonary fibrosis. Particularly, the value of detecting anti-Ro52 antibody in pulmonary fibrosis is unclear., Objective: To evaluate the potential diagnostic value of anti-SSA, anti-SSB, and anti-Ro52 autoantibodies as markers of pSS-related pulmonary fibrosis., Methods: One-hundred seventy-nine patients with pSS were analyzed retrospectively at our hospital. They were divided into the fibrosis and non-fibrosis groups. Pulmonary fibrosis was classified as mild, moderate, or severe based on the patients' computed tomography (CT) findings. Laboratory examinations, including anti-SSA, anti-SSB, and anti-Ro52 antibody evaluations, were performed. The influencing factors of pulmonary fibrosis were analyzed using logistic regression., Results: Chest CT revealed pulmonary fibrosis in 45 patients with pSS (25.1%). The positive rates of anti-SSA and anti-Ro52 antibodies in the fibrosis group were lower than in the non-fibrosis group (P=0.04, P=0.001). The frequency of anti-Ro52 antibody showed no significant differences between mild-to-moderate (53.8%) and severe (47.3%) pulmonary fibrosis. The anti-Ro52 antibody was identified as a potentially protective factor against pSS (P=0.041)., Conclusions: Patients with pSS and pulmonary fibrosis had a low frequency of anti-SSA and anti-Ro52 antibodies. In patients with pSS and negative anti-Ro52 antibody, a chest CT is recommended to further understand the patients' condition.

Aim: Recent studies have shown that anti-Ro52 antibody is associated with both interstitial lung disease (ILD) and the degree of disease severity in juvenile patients with dermatomyositis (DM). We found that more than half of adult patients with DM were positive for anti-Ro52 antibody. In this study, we analysed the correlation between anti-Ro52 antibody and ILD in adult patients with DM., Method: Serum samples were collected from 153 adult inpatients with DM, at the First Medical Centre of PLA General Hospital, Beijing, China, who met the classification criteria of idiopathic inflammatory myopathies from March 1, 2016 to September 30, 2019. The patients were followed up to May 31, 2020. Immunoblotting was used to detect 16 types of myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs) from serum samples. High-resolution computed tomography (HRCT) was used to calculate the ILD score, and tumours were screened. Clinical data and HRCT scores were evaluated and analysed retrospectively., Results: Our results showed that anti-Ro52 antibodies were the most commonly found antibodies in patients with DM, with a positive rate of 52.9%. Anti-Ro52, anti-aminoacyl-tRNA synthetase (anti-ARS), and anti-melanoma differentiation-related gene 5 (anti-MDA5) antibodies were found to be risk factors for ILD development. Anti-Ro52 antibodies had a strong predictive effect on ILD in patients with DM., Conclusion: The occurrence of ILD is highly likely in patients with DM who are positive for the anti-Ro52 antibodies. Thus, anti-Ro52 antibodies is an independent risk factor for ILD in patients with DM., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: To compare the clinical characteristics and identify the longterm outcomes of Chinese patients with different antisynthetase antibodies., Methods: We investigated retrospectively 124 consecutive patients with antisynthetase syndrome. Medical records, laboratory results, and computed tomography images were obtained., Results: The antisynthetase antibodies we investigated were anti-Jo1 (n = 62), anti-PL7 (n = 31), anti-PL12 (n = 12), and anti-EJ (n = 19). The overall prevalence of interstitial lung disease (ILD) reached 94.4% among study patients. Eleven patients (8.9%) developed rapidly progressive ILD (RP-ILD). Eight patients (6.5%) experienced malignancy. RP-ILD was statistically more prevalent in patients with antisynthetase syndrome with anti-PL7 than those without anti-PL7 (p = 0.028). Anti-Ro52-positive patients with antisynthetase syndrome experienced higher frequency of RP-ILD than those without anti-Ro52 (p = 0.001). Further, anti-PL7-positive patients coexisting with anti-Ro52 exhibited more RP-ILD than those without anti-Ro52 (p = 0.001). Patients with antisynthetase syndrome with RP-ILD had a higher proportion of neutrophils in bronchoalveolar lavage fluid and serum ferritin than those without RP-ILD (p = 0.006 and p = 0.013, respectively). Although no differences were observed between the Kaplan-Meier curves of the 4 antisynthetase antibodies subgroups (p = 0.349), the survival rate of patients with anti-PL7 decreased more rapidly in the early stage of longterm followup compared with those with other antisynthetase antibodies. The presence of RP-ILD, malignancy, and elevated serum ferritin was identified to be associated with poor prognosis in patients with antisynthetase syndrome., Conclusion: Our study investigates the clinical phenotypes and outcomes of patients with antisynthetase syndrome with distinct antisynthetase antibodies and highlights the link between the anti-PL7 antibody and RP-ILD.