Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of interstitial lung disease (ILD). However, the causal role of MMPs in ILD pathogenesis remains to be elucidated. This study aimed to investigate the causal effects of circulating MMPs on ILD risk and to evaluate whether immune cell phenotypes mediate this relationship. A comprehensive Mendelian randomization (MR) and mediation analysis was conducted using publicly available data of genome-wide association study (GWAS) summary statistics. Genetic instruments for 6 MMPs (MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, and MMP-12) and 731 immune cell traits were selected. Inverse-variance weighted (IVW) was the primary analytical method, supplemented by other MR techniques. Sensitivity analyses included MR-Egger regression, Cochran Q test, and MR-PRESSO to assess pleiotropy and heterogeneity. Mediation analysis was performed to quantify the proportion of the effect mediated by significant immune cells. Genetically predicted MMP-9 levels showed a significant positive causal effect on ILD risk (odds ratio [OR] = 1.034, 95% confidence interval [CI]: 1.006-1.064, P = .018). Among 731 immune cell phenotypes, 8 were identified as causal for ILD, including effector memory double negative T cells (EM DNT; OR = 1.170, P = .001). MMP-9 was further found to increase the abundance of EM DNT (OR = 1.041, 95% CI: 1.009-1.074, P = .012). Mediation analysis indicated that EM DNT mediated 18.5% of the total effect of MMP-9 on ILD. Sensitivity analyses revealed no evidence of horizontal pleiotropy or significant heterogeneity. This study provides genetic evidence supporting a causal role of MMP-9 in the development of ILD, partially mediated through EM DNT. These findings suggest that MMP-9 and EM DNT could be potential therapeutic targets for preventing or treating ILD.

To evaluate the feasibility and safety as well as potential effects of percutaneous sacral nerve stimulation (SNS) via acupuncture needles in patients with active rheumatoid arthritis (RA). Twenty-one patients with active RA were allocated to receive either active SNS (n = 11) or sham stimulation (n = 10) for 60 min daily over 14 days. Primary outcomes were changes in disease activity, assessed by the Disease Activity Score in 28 joints (DAS-28), tender joint count (TJC), swollen joint count (SJC), pain intensity on a visual analogue scale (VAS), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Secondary outcomes included the following: (1) patient-reported outcomes for joint function, fatigue, anxiety, and depression; (2) serum levels of inflammatory cytokines; and (3) heart rate variability (HRV) parameters as a measure of autonomic function. In this pilot study, the SNS group showed significant within-group improvements in TJC, VAS, DAS28-ESR, and DAS28-CRP. However, an analysis of covariance (ANCOVA) adjusting for baseline values revealed no significant between-group differences in clinical and inflammatory parameters. The SNS group showed a significant increase in rMSSD (parasympathetic marker), with the between-group difference sustained after baseline adjustment. No significant differences were observed in functional and psychological scores or serum cytokine levels between the two groups. This first-in-human study indicates that percutaneous SNS is feasible and safe, with a possible modulatory effect on autonomic function in active RA. Further large‑scale, adequately powered trials are warranted to confirm the clinical efficacy and mechanisms of SNS in RA. This study was registered at ClinicalTrials.gov on March 25, 2021 under the identifier NCT04821050 (Protocol ID: 202002053).

Hydroxychloroquine serves as a foundational medication in the treatment of systemic lupus erythematosus (SLE), exhibiting multiple roles including immune modulation and cardiovascular protection. However, current research on its effect on depressive symptoms in SLE patients remains limited and yields conflicting findings. A single-center cross-sectional study was conducted at the Nanjing First Hospital, Nanjing Medical University between November 1, 2022 and December 30, 2023. A total of 106 adult Chinese patients meeting SLE diagnostic criteria were enrolled. Severity of depressive symptoms was assessed using the Patient Health Questionnaire-9 (PHQ-9), alongside demographic, clinical, pharmacological, and laboratory data collection. Statistical analyses were performed using SPSS 27.0, incorporating univariate and multivariate linear regression analysis. A total of 53.8

OBJECTIVES:To develop and validate a machine-learning (ML) model that flags primary Sjögren's disease (pSjD) patients at high risk of depressive symptoms for earlier clinical attention. METHODS:We retrospectively studied 147 pSjD patients (Nanjing First Hospital, 2019-2022). Depressive symptoms were screened with Patient Health Questionnaire-9 (PHQ-9); PHQ-9 ≥5 was the primary endpoint. Missing data were handled by multiple imputation. Data were split 70/30 for training/testing. After univariate screening and LASSO selection, eight ML algorithms (e.g., logistic regression, support vector machine (SVM), tree/boosting methods) were trained with stratified 10-fold cross-validation. Performance was summarised by AUROC/AUPRC, accuracy, precision/recall, Brier score, and calibration; SHAP provided model explainability. RESULTS:Four routinely available predictors were retained: fatigue frequency, sleep duration, lymphocyte count, and anti-Ro52 status. Across repeated cross-validation, SVM showed the best overall discrimination (mean AUROC≈0.90) with strong precision and accuracy. In the held-out test set, SVM maintained high performance (AUROC=0.929; AUPRC=0.959; Brier=0.106). SHAP confirmed predictor importance, indicating higher risk with shorter sleep, lower lymphocyte counts, greater fatigue frequency, and anti-Ro52 positivity. CONCLUSIONS:This study presents the first ML-based model for predicting depressive symptoms in pSjD patients, highlighting the significance of immuno-inflammatory and clinical factors in depression pathogenesis. The SVM model offers a robust, non-invasive tool for early identification of high-risk individuals, enabling timely and personalised interventions. However, this single-centre, retrospective design with a modest sample limits generalisability; therefore, independent multi-centre validation is required before clinical use.

This study retrospectively collected clinical data from 480 patients with connective tissue diseases (CTDs) at Nanjing First Hospital between August 2019 and December 2023 to develop and validate a multi-classification machine learning (ML) model for assessing depression risk. Addressing the limitations of traditional assessment tools, six ML models were constructed using univariate analysis and the LASSO algorithm, with the categorical boosting (Catboost) model emerging as the best performer, demonstrating strong predictive ability across different depression severity levels (none_F1 = 0.879, mild_F1 = 0.627, moderate and severe_F1 = 0.588). Additionally, the study provided an interpretation of the best-performing model using SHAP and developed a user-friendly R Shiny application ( https://macnomogram.shinyapps.io/Catboost/ ) to facilitate clinical use. The findings suggest that the Catboost model represents a significant advancement in assessing depression risk among CTD patients, highlighting the potential of ML in enhancing mental health management for this patient population.

Introduction Antinuclear antibodies (ANA) are frequently positive in patients with anti-melanoma differentiation-associated gene 5-positive dermatomyositis (anti-MDA5+ DM). This study aimed to investigate the association between ANA and clinical characteristics as well as prognosis in a cohort of patients with anti-MDA5+ DM. Material and methods We conducted a systematic retrospective study of medical records from a Nanjing Medical University cohort of patients with myositis-associated interstitial lung disease (ILD). Various parameters were compared and analyzed between the ANA-positive group and the ANA-negative group. Results A total of 246 patients with anti-MDA5+ DM were enrolled in this study, with 28.5% males and 71.5% females. The median age was 53.0 years, the median disease duration was 2 months, and the median follow-up period was 12.0 months. The ANA positivity rate at baseline was 52.4% in anti-MDA5+ DM patients. The ANA-positive group showed significantly higher positivity rates of anti-Ro52 antibodies (72.9% vs. 54.7%, p = 0.003) and anti-aminoacyl-tRNA synthetase (anti-ARS) antibodies (9.3% vs. 2.6%, p = 0.033) compared to the ANA-negative group, but lower ALT levels: 39.0 (21.5, 79.3) vs. 51.3 (36.5, 95.8), p = 0.006. No significant differences were observed between the two groups in terms of overall survival, rapidly progressive interstitial lung disease (RPILD) incidence, age, disease duration, and clinical characteristics. In a subgroup analysis of the ANA-positive group, MDA5+++ patients had a higher incidence of RPILD compared to the MDA5+ group ( p = 0.028). In the ANA-negative subgroup analysis, MDA5+++ patients had a higher mortality rate and worse prognosis compared to the MDA5+ group ( p = 0.026). Multivariate Cox regression analysis showed that elevated lactate dehydrogenase (LDH) levels and the presence of rapidly progressive interstitial lung disease (RPILD) were associated with poor prognosis in ANA-negative anti-MDA5+ DM patients, with hazard ratios of 1.002 (95% CI: 1.001, 1.003, p = 0.020) and 13.694 (95% CI: 15.032, 37.267, p < 0.001), respectively. Conclusions ANA is frequently found in patients with anti-MDA5+ DM. High titers of anti-MDA5 antibodies are associated with mortality and RPILD.

This study retrospectively collected clinical data from 480 patients with connective tissue diseases (CTDs) at Nanjing First Hospital between August 2019 and December 2023 to develop and validate a multi-classification machine learning (ML) model for assessing depression risk. Addressing the limitations of traditional assessment tools, six ML models were constructed using univariate analysis and the LASSO algorithm, with the artificial neural network (ANN) model emerging as the best performer, demonstrating strong predictive ability across different depression severity levels (none_F1=0.849, mild_F1=0.621, moderate and severe_F1=0.571). Additionally, the study provided an interpretation of the best-performing model using SHAP and developed a user-friendly R Shiny application (https://macnomogram.shinyapps.io/ANN-CTD/) to facilitate clinical use. The findings suggest that the ANN model represents a significant advancement in assessing depression risk among CTD patients, highlighting the potential of ML in enhancing mental health management for this patient population.

Epidemiological and observational studies have indicated an association between rheumatoid arthritis (RA) and pulmonary arterial hypertension (PAH). However, consistent conclusions have not been reached due to various limitations. In order to determine whether RA and PAH are causally related, we conducted a Mendelian randomization (MR) study with two samples. Data for overall RA (13,621 cases and 262,844 controls), seropositive RA (5103 cases and 402,554 controls), seronegative RA (4192 cases and 311,210 controls), and PAH (248 cases and 289,117 controls) derived from the FinnGen consortium. The inverse variance weighted, along with four other effective methodologies, were employed to comprehensively infer the causal relationships between RA and PAH. To assess the estimation's robustness, a number of sensitivity studies were performed. Causal genetic association was found between seropositive RA and decreased risk of PAH (odds ratio (OR) = 0.812, 95

Objective To explore the risk factors of anxiety and depression, especially their association with serum autoantibodies, in patients with connective tissue diseases (CTDs). Methods Three hundred and fifty-two inpatients with CTDs were recruited and their demographic, serological and imaging data were collected through the medical record system. Depression and anxiety were assessed by the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 Scale (GAD-7) respectively. Analysis of variance (ANOVA), rank sum test, chi-square test and logistic regression were performed to investigate risk factors for depression and anxiety. Results The prevalence of depression (PHQ-9 >= 5) and anxiety (GAD-7 >= 5) in CTD patients was significantly higher than that in the Chinese general population (depression: 44.3% vs. 32.2%, anxiety: 39.5% vs. 22.2%). Sleep time was a protective factor for both depression and anxiety (OR=0.734, 95% CI: 0.616-0.874, p<0.001 and OR=0.684, 95% CI: 0.559-0.835, P<0.001, respectively) while anti-Ro52 antibody was a risk factor for them (OR=5.466, 95% CI: 2.978-10.032, p<0.001 and OR=4.075, 95% CI: 2.073-8.010, p<0.001, respectively). Further analysis showed that anti-Ro52 antibody was a risk factor for depression and anxiety in all four subgroups, namely SLE, SS, RA, and other CTDs. Conclusion Anti-Ro52 antibody is probably a risk factor for depression and anxiety in patients with connective tissue diseases. CTD patients with the presence of anti-Ro52 antibody are more prone to depression and anxiety than those without it.

Objective: To explore the association of disease activity, as evaluated by both the Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) and the SLEDAI-2000 (SLEDAI-2K), with depression and anxiety in patients with SLE. Methods: A cross-sectional study was conducted among 85 Chinese patients with SLE. Disease activity was measured using SLEDAI-2K and SLE-DAS scoring systems. Depression and anxiety were assessed using Patient Health Questionnaire-9 and Generalized Anxiety Disorder Scale-7, respectively. Multivariate logistic regression analysis was performed to evaluate the association of disease activity scores, as well as specific clinical and laboratory items, with depression and anxiety. Results: There was a robust correlation between SLEDAI-2K and SLE-DAS scores in overall patient population (Spearman's r = 0.764, 95% CI 0.655-0.842; P < 0.001) and in those with moderate-to-high disease activity (Spearman's r = 0.792, 95% CI 0.616-0.892; P < 0.0001). However, the correlation weakened for patients with mild disease activity or remission (Spearman's r = 0.450, 95%CI 0.188-0.652; P = 0.001). Multivariate logistic regression analysis did not show a significant correlation between SLEDAI-2K and SLE-DAS scores and depression/anxiety. The presence of mucosal ulcer/serositis significantly increased the risk of depression (odds ratio = 4.472, 95% CI 1.035-19.328; P = 0.045) and anxiety (odds ratio = 3.978, 95% CI 1.051-15.049; P = 0.042). Conclusion: The SLE-DAS scoring system demonstrated a comparable ability to assess disease activity in SLE compared with SLEDAI-2K. Though neither scoring system showed significant associations with depression and anxiety, the presence of mucosal ulcer/serositis markedly heightened the risk of both among SLE patients.

BackgroundThe prognosis of anti-melanoma differentiation-associated gene 5 positive dermatomyositis (anti-MDA5+DM) is poor and heterogeneous. Rapidly progressive interstitial lung disease (RP-ILD) is these patients’ leading cause of death. We sought to develop prediction models for RP-ILD risk in anti-MDA5+DM patients.MethodsPatients with anti-MDA5+DM were enrolled in two cohorts: 170 patients from the southern region of Jiangsu province (discovery cohort) and 85 patients from the northern region of Jiangsu province (validation cohort). Cox proportional hazards models were used to identify risk factors of RP-ILD. RP-ILD risk prediction models were developed and validated by testing every independent prognostic risk factor derived from the Cox model.ResultsThere are no significant differences in baseline clinical parameters and prognosis between discovery and validation cohorts. Among all 255 anti-MDA5+DM patients, with a median follow-up of 12 months, the incidence of RP-ILD was 36.86%. Using the discovery cohort, four variables were included in the final risk prediction model for RP-ILD: C-reactive protein (CRP) levels, anti-Ro52 antibody positivity, short disease duration, and male sex. A point scoring system was used to classify anti-MDA5+DM patients into moderate, high, and very high risk of RP-ILD. After one-year follow-up, the incidence of RP-ILD in the very high risk group was 71.3% and 85.71%, significantly higher than those in the high-risk group (35.19%, 41.69%) and moderate-risk group (9.54%, 6.67%) in both cohorts.ConclusionsThe CROSS model is an easy-to-use prediction classification system for RP-ILD risk in anti-MDA5+DM patients. It has great application prospect in disease management.

IntroductionTo identify the clinical characteristics and risk factors for cutaneous ulcers in patients with anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis (anti-MDA5+ DM) combined with rapidly progressive interstitial lung disease (RPILD).Material and methodsWe conducted a retrospective cohort study on the medical records of patients enrolled from the Nanjing Medical University Myositis-associated ILD cohort (NMMI). The clinical characteristics of patients in the ulcer-positive group were compared with those in the ulcer-negative group by chi-square or Fisher’s exact test. Univariate and multivariate logistic regression analyses were used to assess risk factors for the development of cutaneous ulcers.ResultsA total of 246 patients with anti-MDA5+ DM were retrospectively enrolled in the study, including 176 females (176/246, 71.54%) and 70 males (70/246, 28.46%), with a female-to-male ratio of 2.51 : 1. Among the 246 patients, a total of 88 cases (88/246, 35.77%) with anti-MDA5+ DM combined with RPILD were further studied, including 55 females (55/88, 62.5%) and 33 males (33/88, 37.5%), with a female-to-male ratio of 1.67 : 1. Twelve patients (12/88, 13.64%) had cutaneous ulcers. In terms of clinical characteristics, patients in the ulcer-positive group had significantly more proximal muscle involvement (83.33% vs. 38.16%, p = 0.003) and more heliotrope rash (83.33% vs. 43.42%, p = 0.010) than in the ulcer-negative group. In univariate analysis, cutaneous ulcers were associated with proximal muscle involvement (OR = 8.103; 95% CI: 1.657–39.625; p = 0.010) and heliotrope rash (OR = 6.515; 95% CI: 1.336–31.773; p = 0.020). In multivariate analysis, cutaneous ulcers were associated with proximal muscle involvement (OR = 6.436; 95% CI: 1.274–32.524; p = 0.024), and proximal muscle involvement was an independent risk factor for cutaneous ulcers.ConclusionsWe confirmed the association between cutaneous ulcers and proximal muscle involvement and heliotrope rash in patients with anti-MDA5+ DM combined with RPILD. Proximal muscle involvement is an independent risk factor for cutaneous ulcers.

ABSTRACTThis study aimed to explore the potential causal link between genetic predisposition to various connective tissue diseases (CTDs), namely systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), polymyositis (PM), dermatomyositis (DM), systemic sclerosis (SSc), mixed connective tissue disease (MCTD), and rheumatoid arthritis (RA), and the incidence of pulmonary arterial hypertension (PAH) utilizing Mendelian randomization (MR). Employing a two‐sample MR approach, genetic variants associated with CTDs served as instrumental variables to investigate the exposure‐outcome relationship, with GWAS data sourced from the FinnGen Biobank. Comprehensive statistical analyses, including the inverse variance weighted (IVW) method, were conducted, alongside heterogeneity, pleiotropy, and sensitivity tests to ensure the robustness and validity of findings. The results revealed that in the Finnish population, no significant causal associations were identified between PAH and SLE, SS, PM, DM, MCTD, or RA. Notably, a significant association was observed between SSc and an increased risk of PAH (IVW: OR = 1.278, 95% CI = 1.061–1.540, p = 0.010). However, this finding was not replicated in other European populations. These results indicate the unique genetic and pathological pathways underlying SSc‐associated PAH, emphasizing the need for tailored screening and management protocols in this patient group.

ObjectiveInterstitial lung disease (ILD) is a common extramuscular complication contributing to significant morbidity and mortality in patients with dermatomyositis (DM) who are positive for antimelanoma differentiation–associated gene 5 antibody (anti-MDA5+). We conducted this study to investigate the association of anti-Ro52 antibodies with clinical characteristics and prognosis in patients with anti-MDA5+ DM.MethodsWe assessed a cohort of 246 patients with anti-MDA5+ DM. To calculate hazard ratios and 95% CIs for rapidly progressive ILD (RP-ILD) and death while controlling for potential confounders, variables selected by univariate Cox regression analysis were included in a multivariate Cox regression model with the stepwise forward-selection method. A 2-tailed analysis withP< 0.05 was considered to be statistically significant.ResultsA total of 246 patients with anti-MDA5+ DM were enrolled; 70 patients were male, and the patient group had an average age of 53.1 (12.4) years. Anti-Ro52 was present in 64.2% (158/246) patients. Patients with anti-MDA5+ DM who were positive for anti-Ro52 had a higher rate of RP-ILD (log-rankP< 0.001) and a higher mortality rate (log-rankP= 0.01). For patients with anti-MDA5+ DM who were positive for anti-Ro52, those with a short disease course and high inflammation were at increased risk of RP-ILD and death. The appearance of active rash was an independent protective factor of death.ConclusionAnti-Ro52 antibodies were highly prevalent in patients with anti-MDA5+ DM, and their coexistence correlated with a higher rate of RP-ILD and mortality. Patients with a short disease course, with increased inflammation, and without rash were more likely to have a poor prognosis.

OBJECTIVE:To investigate the impact of sex differences on the clinical characteristics and prognosis of patients with anti-melanoma differentiation-associated gene 5-positive dermatomyositis (MDA5+ DM).METHODS:We retrospectively analyzed a cohort of 251 patients with MDA5+ DM, including 71 in the male group and 180 in the female group. A multivariate logistic regression model was built to analyze independent risk factors for RPILD in each group. An ROC curve was drawn to evaluate the predictive value of independent risk factors. Kaplan‒Meier analysis was used to compare the cumulative survival rates, while the log-rank test was used to test for significant differences between the two groups.RESULTS:Patients in the male group had a significantly higher prevalence of heliotrope rash, V sign, severe interstitial lung disease (ILD), and rapidly progressive interstitial lung disease (RPILD) than those in the female group. Anti-Ro52 positivity, high CRP level and short disease were identified as independent risk factors for RPILD in both male and female groups by multivariate logistic regression analysis. The mortality rates of males and females were 33.8% and 22.0%, respectively, and the survival time of patients in the male group was shorter than that in the female group.CONCLUSION:Male patients with MDA5+ DM exhibit an increased risk of RPILD, elevated mortality rates and reduced overall survival time compared to their female counterparts, and anti-Ro52 positivity may be an unfavorable prognostic factor for these patients. Key Points • The prevalence of solar rash, V sign, severe interstitial lung disease (ILD) and rapidly progressive interstitial lung disease (RPILD) in anti-MDA5-positive female patients was significantly lower than that in male patients. • Positive Anti-Ro52, high CRP level, and short course of disease were independent risk factors for RPILD in both men and women. • Female patients exhibited a lower mortality rate than male patients (22.0% vs 33.8%) and demonstrated longer survival time.

Abstract The risk of mental disorders such as depression and anxiety is increased in connective tissue diseases (CTDs). However, little is known about whether this risk is related to autoantibodies. We conducted an observational, single-center, cross-sectional study to investigate the correlation of depression and anxiety with the presence of autoantibodies in patients with CTDs. Three hundred and fifty-two inpatients with CTDs were recruited and their demographic, serological and imaging data were collected through the medical record system. Depression and anxiety were assessed by the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 Scale (GAD-7) respectively. Analysis of variance (ANOVA), rank sum test, chi-square test and logistic regression were performed to investigate risk factors for depression and anxiety. The prevalence of depression (PHQ-9 ≥ 5) and anxiety (GAD-7 ≥ 5) in CTD patients was significantly higher than that in the Chinese general population (depression: 44.3% vs 32.2%, anxiety: 39.5% vs 22.2%). Sleep time was a protective factor for both depression and anxiety (OR = 0.719, 95% CI: 0.605 ~ 0.856, P = 0.0002 and OR = 0.639, 95% CI: 0.528 ~ 0.773, P < 0.0001, respectively) while anti-Ro52 antibody was a risk factor for them (OR = 5.545, 95% CI: 3.053 ~ 10.074, P < 0.001 and OR = 5.642, 95% CI: 3.071 ~ 10.363, P < 0.0001, respectively). Further analysis showed that anti-Ro52 antibody was a risk factor for depression and anxiety in all four subgroups, namely SLE, SS, RA, and other CTDs. CTD patients with the presence of anti-Ro52 antibody are more prone to depression and anxiety than those without it.

OBJECTIVE:There is substantial heterogeneity among the phenotypes of patients with anti-melanoma differentiation-associated gene 5 antibody-positive (anti-MDA5+) dermatomyositis (DM), hindering disease assessment and management. This study aimed to identify distinct phenotype groups in patients with anti-MDA5+ DM and to determine the utility of these phenotypes in predicting patient outcomes. METHODS:A total of 265 patients with anti-MDA5+ DM were retrospectively enrolled in the study. An unsupervised hierarchical cluster analysis was performed to characterize the different phenotypes. RESULTS:Patients were stratified into 3 clusters characterized by markedly different features and outcomes. Cluster 1 (n = 108 patients) was characterized by mild risk of rapidly progressive interstitial lung disease (RPILD), with the cumulative incidence of non-RPILD being 85.2%. Cluster 2 (n = 72 patients) was characterized by moderate risk of RPILD, with the cumulative incidence of non-RPILPD being 73.6%. Patients in cluster 3 (n = 85 patients), which was characterized by a high risk of RPILD and a cumulative non-RPILD incidence of 32.9%, were more likely than patients in the other 2 subgroups to have anti-Ro 52 antibodies in conjunction with high titers of anti-MDA5 antibodies. All-cause mortality rates of 60%, 9.7%, and 3.7% were determined for clusters 3, 2, and 1, respectively (P < 0.0001). Decision tree analysis led to the development of a simple algorithm for anti-MDA5+ DM patient classification that included the following 8 variables: age >50 years, disease course of <3 months, myasthenia (proximal muscle weakness), arthritis, C-reactive protein level, creatine kinase level, anti-Ro 52 antibody titer, and anti-MDA5 antibody titer. This algorithm placed patients in the appropriate cluster with 78.5% accuracy in the development cohort and 70.0% accuracy in the external validation cohort. CONCLUSION:Cluster analysis identified 3 distinct clinical patterns and outcomes in our large cohort of anti-MDA5+ DM patients. Classification of DM patients into phenotype subgroups with prognostic values may help physicians improve the efficacy of clinical decision-making.

Objectives Anti-melanoma differentiation-associated gene 5 positive (anti-MDA5+) DM has a close relationship with rapidly progressive interstitial lung disease (RPILD) and is associated with high mortality. However, data regarding the time-dependent risk of RPILD and deaths during disease progression are limited. We conducted this study to investigate whether the risk of RPILD and death were time-dependent or not in anti-MDA5+ DM. Methods We assessed a cohort of 272 patients with anti-MDA5+ DM. The clinical characteristics of patients with anti-MDA5+ were collected, and COX regression was used to analyse independent risk factors for RPILD and death. We also described changes in risk of RPILD and death over time and their potential clinical implications. Results There were 272 anti-MDA5+ DM patients enrolled in this study. According to the multivariate cox regression analysis, short disease course, high CRP level, anti-Ro52 positive and anti-MDA5 titre (++similar to+++) were independent risk factors of RPILD. High creatine kinase level, high CRP level and RPILD were independent risk factors for death, and >90% RPILD and 84% mortality occurred in the first 6 months after disease onset. Notably, the first 3 months is a particularly high-risk period, with 50% of RPILD and 46% of deaths occurring. Hazards regarding RPILD and mortality diminished over time during a median follow-up of 12 months. Conclusion These results suggest significant, time-dependent changes in RPILD and mortality risk in anti-MDA5+ DM patients, providing a cut-off time window to estimate disease progression and poor prognosis.

目的 目前维生素D在类风湿关节炎(RA)患者中的作用机制尚未明确.研究RA患者外周血清25-羟维生素D[25(OH)D]浓度与疾病活动度的关系;明确体外给予活性维生素D[1,25(OH)2D3,VD]干预是否可抑制人类滑膜成纤维细胞系(MH7A)炎性细胞因子的释放及探讨可能的抗炎机制.方法 回顾分析2019年5月至2020年5月南京市第一医院风湿免疫科住院的类风湿关节炎患者血清93份(RA组),以及同期正常体检者血清48份(健康组),患者血清为RA组,健康体检者血清为健康组.用质谱法检测血清25(OH)D的浓度值,比较两组值之间的差异.并记录以上93例住院患者的临床指标,包括:类风湿因子、抗环瓜氨酸多肽抗体、血沉、C反应蛋白、血钙、压痛关节数、肿胀关节数和25(OH)D水平.按疾病活动度DAS28评分将93份数据分为缓解组、中低活动组和高活动组;按血清25(OH)D浓度将93份数据分为25(OH)D正常组、25(OH)D不足组和25(OH)D缺乏组.统计不同疾病活动度与不同血清25(OH)D浓度及临床指标之间的相关性.体外培养MH7A细胞,将实验分为3组,对照组:不加任何处理;刺激组:用脂多糖(LPS,100 ng/mL)刺激细胞5 h,模拟RA的体外炎症环境;干预组:将LPS和VD(10-8mol/L)与细胞共培养24 h.采用RT-qPCR和ELISA法检测MH7A细胞产生炎性细胞因子(TNF-α,IL-1β,IL-6)mRNA和蛋白水平以及miR-155水平,统计分析3组之间炎性因子及miR-155表达的差异.结果 RA组血清25(OH)D水平[(15.8±6.01)ng/mL)]较健康组[(30.5±3.80)ng/mL]明显降低(P<0.01).疾病高活动组的血清25(OH)D水平低于缓解组和中低活动组(P<0.05),而ESR、CRP、TJC和SJC高于缓解组和中低活动组(P<0.05);中低活动组的血清25(OH)D水平低于缓解组(P<0.05),而ESR、CRP、TJC和SJC高于缓解组(P<0.05).血清25(OH)D缺乏组的DAS28、ESR、CRP、TJC和SJC高于另外2组(P<0.05).血清25(OH)D与高ESR(r=-0.485,P<0.01);高CRP(r=-0.667,P<0.01);低血Ca(r=0.548,P<0.01);高TJC(r=-0.563,P<0.01);高SJC(r=-0.466,P<0.01)及高DAS28评分(r=-0.761,P<0.01)相关.LPS刺激MH7A细胞后,与对照组比较,刺激组炎性细胞因子(TNF-α,IL-1β,IL-6)的mRNA及蛋白表达水平升高(P<0.01);与刺激组比较,干预组的炎性细胞因子的mRNA及蛋白表达水平下调(P<0.01).RT-qPCR检测,与对照组miR-155表达(1.00±0.00)比较,刺激组(3.86±0.07)升高(P<0.01),而干预组较刺激组表达(2.22±0.10)被下调(P<0.01).结论 RA患者血清25(OH)D水平较正常健康人群明显偏低,且与疾病活动度负相关.给予外源性VD干预后可抑制MH7A产生的炎性细胞因子水平,并下调miR-155的表达.

OBJECTIVES To investigate the association of serum interleukin-11 (IL-11) with disease activity and occurrence of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA). METHODS One hundred and six RA patients were included, including 31 with ILD. All patients were divided into two groups according to the 28-joint Disease Activity Score (DAS28), active-disease group (DAS28>3.2) and target-achieved group (DAS28≤3.2). Serum IL-11 was detected by ELISA. Serum autoantibodies [anticitrullinated protein antibody (ACPA) and rheumatoid factor (RF)], inflammatory markers [C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)], and complete blood count were measured with routine methods. RESULTS Serum IL-11 was upregulated in RA patients compared with healthy controls (HC), and increased more significantly in patients with ILD (RA-ILD) than patients without ILD (RA-nonILD). In both RA-ILD and RA-nonILD patients, serum level of IL-11 was higher in the active-disease group than that in the target-achieved group. Pearson correlation analysis confirmed that IL-11 was positively correlated with DAS28. No significant correlation was found between serum level of IL-11 and ACPA or RF. IL-11 was positively correlated with ESR and CRP levels and PLT count in RA patients. CONCLUSIONS IL-11 was found to be involved in the development of arthritis and ILD in RA patients, and might constitute a potential target for the treatment of RA-ILD.