Clinical RheumatologyPub Date : 2025-09-01Epub Date: 2025-07-16DOI: 10.1007/s10067-025-07558-x
Yi Wei, Yansong Huang, Xu Wang, Lina Zhang, Kunyu Zheng, Yunjiao Yang, Yanlei Yang, Chengmei He, Lin Qiao, Yongzhe Li, Fengchun Zhang, Li Wang
{"title":"Postpartum may be a risk factor for biochemical flares in patients with primary biliary cholangitis: A single-center experience.","authors":"Yi Wei, Yansong Huang, Xu Wang, Lina Zhang, Kunyu Zheng, Yunjiao Yang, Yanlei Yang, Chengmei He, Lin Qiao, Yongzhe Li, Fengchun Zhang, Li Wang","doi":"10.1007/s10067-025-07558-x","DOIUrl":"10.1007/s10067-025-07558-x","url":null,"abstract":"<p><strong>Background and aims: </strong>Pregnancy and fetal outcomes in patients with primary biliary cholangitis (PBC) have garnered insufficient attention due to relatively rare in women of reproductive age. In this study, intricate relationship between PBC and pregnancy were investigated.</p><p><strong>Methods: </strong>Twenty pregnant patients with PBC under long-term follow-up in Peking Union Medical College Hospital were enrolled, which pregnancy and fetal outcomes were retrospectively analyzed.</p><p><strong>Results: </strong>Among the 28 pregnancies, 5 (17.9%) resulted in miscarriages, whereas 23 were live births (82.1%, including 21 full-term and two premature births). Notably, no post-mature births or stillbirths occurred. Adverse maternal events were observed in 6 cases (6/28, 21.4%), and adverse postpartum events occurred in 3 cases (3/28, 10.7%). Most patients with PBC (7/10, 70%) maintained relatively stable biochemical measures during pregnancy. However, up to 60% (6/10) of the patients experienced biochemical flares within the first 6 months postpartum. 4 patients continued to take ursodeoxycholic acid (UDCA) during pregnancy without encountering any adverse maternal or infant outcomes.</p><p><strong>Conclusions: </strong>Most patients with PBC (70%) were able to maintain stable biochemical parameters during pregnancy, with good maternal and infant outcomes. Nevertheless, 60% of the patients with PBC experienced biochemical flares within the first 6 months postpartum, so close monitoring is necessary. UDCA treatment appears to be safe during pregnancy. Key Points • This retrospective study focuses on peripartum safety in reproductive-age patients with PBC during pregnancy. • Although most patients with PBC could maintain biochemical stability during pregnancy, a significant number of patients experienced biochemical flares within the first 6 months postpartum. • UDCA treatment appears to be safe during pregnancy in patients with PBC.</p>","PeriodicalId":10482,"journal":{"name":"Clinical Rheumatology","volume":" ","pages":"3733-3742"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The association between STAT4 polymorphism and pulmonary arterial hypertension in Chinese patients with primary Sjögren's syndrome.","authors":"Min Hui, Xiaoyue Deng, Jieying Wang, Junyan Qian, Jiuliang Zhao, Qian Wang, Yongtai Liu, Zhuang Tian, Dong Xu, Mengtao Li, Xiaofeng Zeng","doi":"10.1007/s10067-025-07580-z","DOIUrl":"10.1007/s10067-025-07580-z","url":null,"abstract":"<p><strong>Objective: </strong>Primary Sjögren's syndrome (pSS) was one of the pivotal causes of pulmonary arterial hypertension (PAH) among connective tissue diseases (CTDs) with adverse outcomes, but genetic studies of pSS-PAH are quite limited. Studies have identified genetic predisposition in both familial PAH (fPAH) and idiopathic PAH (iPAH) cases. Therefore, the aim of this study was to explore the genetic susceptibility of PAH in pSS.</p><p><strong>Methods: </strong>Forty-three pSS-PAH patients, 92 pSS-non-PAH patients, and 105 healthy controls (HC) were obtained. PAH was diagnosed according to the 2015 European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines, and ruled out by echocardiogram as estimated PAP < 40 mmHg. Single-nucleotide polymorphism (SNP) sites related to PAH and pSS were selected and then compared between pSS-PAH and pSS-non-PAH groups.</p><p><strong>Results: </strong>In pSS-PAH group, 97.7% of the patients were female and average age of PAH onset was 37.3 ± 10.6 years. The allele frequency of STAT4 rs10168266 was markedly different between pSS-PAH and pSS-non-PAH groups (p = 0.027, OR = 0.547), with the genotypic frequency of CC/CT/TT 47.6%/38.1%/14.3% versus 25.6%/53.3%/21.1%. While C-allele was much more frequent in pSS-PAH group than in pSS-non-PAH group (66.7% vs. 52.2%), the intron variant rs10168266 (C > T) of signal transductor and activator of transcription (STAT4) gene was speculated to be a protective factor for PAH in pSS patients. A remarkable divergence was also proven in the dominant and additive hereditary model tests between pSS-PAH and pSS-non-PAH groups (p = 0.012, OR = 0.378).</p><p><strong>Conclusion: </strong>SNP sites identified by genome-wide association study (GWAS) in pSS, especially STAT4 rs1016826, was verified to be correlated with pSS-PAH. Further investigations on the mechanisms were called for early diagnosis and innovative therapeutic targets.</p>","PeriodicalId":10482,"journal":{"name":"Clinical Rheumatology","volume":" ","pages":"3581-3590"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Identifying plasma proteins and immunocyte phenotypes as risk factors in rheumatoid arthritis: The role of EPHA3 and CD28<sup>+</sup> CD45RA<sup>+</sup> CD8<sup>br</sup> treg cells.","authors":"Yanqiu Zhang, Yuting Liang, Mengxue Liu, Lili Liu, Jun Li, Ruyu Li, Ziqi Wu, Longwei Qiao, Jingyu Chen","doi":"10.1007/s10067-025-07605-7","DOIUrl":"10.1007/s10067-025-07605-7","url":null,"abstract":"<p><strong>Objectives: </strong>Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease whose pathogenesis involves the participation of numerous plasma proteins and immune cells, but their relationships are unclear. So we set out to thoroughly examine the causal link between 4907 plasma proteins and RA and to identify the involvement of 731 immunocyte phenotypes as potential mediators.</p><p><strong>Methods: </strong>Using publicly available genome-wide association studies (GWAS) data, 5 Mendelian randomization (MR) methods (inverse variance weighted (IVW), weighted median, MR-Egger, simple mode, weighted mode) were applied for analysis, along with sensitivity analyses.</p><p><strong>Results: </strong>27 plasma proteins and 10 immunocyte phenotypes were causally linked to RA, with most of the proteins serving as drug targets. Ephrin type-A receptor 3 (EPHA3) was a significant risk factor for RA (odds ratio (OR) = 1.312, 95% confidence interval (CI) [1.102, 1.562], Beta = 0.272, p < 0.01). CD28 on CD28<sup>+</sup> CD45RA<sup>+</sup> CD8<sup>br</sup> regulatory T (Treg) cells mediated the relationship between EPHA3 levels and RA risk, with a mediation effect of 0.029 (95% CI: -0.111, 0.169), accounting for 10.7% of total effect. Moreover, Sensitivity analyses further supported the robustness of these findings.</p><p><strong>Conclusion: </strong>Plasma proteins and immunocyte phenotypes linked to RA have been identified using MR, including EPHA3, which may elevate RA risk by influencing CD28 on CD28<sup>+</sup> CD45RA<sup>+</sup> CD8<sup>br</sup> Treg cells. This could improve RA diagnosis and targeted therapies. Key Points • CD28 on CD28+ CD45RA+ CD8br Treg cells mediates the association between EPHA3 levels and RA risk, highlighting a novel pathway in RA pathogenesis.</p>","PeriodicalId":10482,"journal":{"name":"Clinical Rheumatology","volume":" ","pages":"3525-3537"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Clinical RheumatologyPub Date : 2025-09-01Epub Date: 2025-07-11DOI: 10.1007/s10067-025-07569-8
Zi-Ping Cai, Hong-Yang Wu, Dong-Ge Han, Qiao-Yun Tong, Wei Liu
{"title":"Clinical features and risk factors of abdominal IgA vasculitis in adults.","authors":"Zi-Ping Cai, Hong-Yang Wu, Dong-Ge Han, Qiao-Yun Tong, Wei Liu","doi":"10.1007/s10067-025-07569-8","DOIUrl":"10.1007/s10067-025-07569-8","url":null,"abstract":"<p><strong>Background: </strong>Adult-onset abdominal IgA vasculitis (A-IgAV) presents with abdominal pain as the initial symptom, which is a relatively rare condition that is frequently misdiagnosed.</p><p><strong>Methods: </strong>This retrospective study utilized clinical data from 125 adult patients diagnosed with IgA vasculitis (IgAV), retrieved from the electronic medical records of the First College of Clinical Medical Science, China Three Gorges University. The study comprehensively investigated the clinical manifestations, evaluated the diagnostic significance of various laboratory markers, and identified features from abdominal CT and endoscopy.</p><p><strong>Results: </strong>Of the 125 cases analyzed, 42 involved gastrointestinal (GI) complications, while the remaining 83 did not. A-IgAV predominantly affected younger male patients, with a median age of 37, whereas non-abdominal IgA vasculitis (NA-IgAV) was more common in middle-aged women, with a median age of 47. Patients with purpuric lesions affecting two or more areas of the body were statistically more likely to develop GI complications. Elevated white blood cell (WBC) and C-reactive protein/albumin ratio (CAR) levels, along with reduced immunoglobulin M (IgM), were found to be strong predictors of GI complications, offering substantial prognostic value when WBC exceeded 10.340 × 10<sup>9</sup>/L or CAR surpassed 0.355. Imaging and endoscopy identified the duodenum and ileum as the most commonly affected sites. Endoscopic evaluations frequently revealed mucosal erosion, ecchymosis, ulceration, or hemorrhage, while abdominal CT scans often showed thickening of the intestinal wall.</p><p><strong>Conclusions: </strong>The duodenum is the most frequently affected site, followed by the ileum and jejunum. Multi-regional purpura, leukocytosis, or elevated CAR are independent risk factors for GI involvement. Key Points • The duodenum is the most predominantly involved site, followed by the ileum and jejunum. • Purpura affecting two or more regions significantly increased the likelihood of GI involvement. • WBC and CAR were identifed as risk factors, while IgM was identified as a protective factor.</p>","PeriodicalId":10482,"journal":{"name":"Clinical Rheumatology","volume":" ","pages":"3639-3648"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Clinical RheumatologyPub Date : 2025-09-01Epub Date: 2025-07-19DOI: 10.1007/s10067-025-07582-x
Jian Huang, Lu Wang, Xiaodong Hu, Tianrui Wang, Yingze Zhang
{"title":"Genetic and molecular underpinnings of the link between rheumatoid arthritis and myasthenia gravis: Insights from GWAS and transcriptomic analyses.","authors":"Jian Huang, Lu Wang, Xiaodong Hu, Tianrui Wang, Yingze Zhang","doi":"10.1007/s10067-025-07582-x","DOIUrl":"10.1007/s10067-025-07582-x","url":null,"abstract":"<p><strong>Background: </strong>Although studies have shown that patients with rheumatoid arthritis (RA) are at a higher risk of developing myasthenia gravis (MG), the causal relationship and shared genetic basis between these two diseases have not been fully investigated. The purpose of this study is to uncover the potential bidirectional causality between RA and MG, and to explore their shared genetic factors and possible pathogenic mechanisms.</p><p><strong>Methods: </strong>First, we utilized genome-wide association (GWAS) data from the IEU Open GWAS project, employing the online analysis platform MRBASE and applying four Mendelian randomization (MR) methods (Inverse Variance Weighted regression, Weighted Median, MR-Egger, and Weighted Mode) to explore the bidirectional causal relationship between RA and MG. Subsequently, we extracted transcriptomic data for RA and MG from the GEO database and used differential expression analysis, weighted gene coexpression network analysis (WGCNA), machine learning, and gene set enrichment analysis (GSEA) to identify key hub genes and their associated pathways. Furthermore, we employed the CIBERSORT method to analyze the immune cell infiltration in both diseases. Ultimately, based on these identified hub genes, we constructed a diagnostic model-nomogram-to aid in the diagnosis and prediction of the diseases.</p><p><strong>Result: </strong>RA is significantly associated with an increased risk of MG (Odds Ratio [OR]: 1.353, 95% Confidence Interval [CI]: 1.081 to 1.693, P = 0.008). However, there is insufficient evidence to support the hypothesis that MG increases the risk of RA. Through differential expression analysis and WGCNA methods, we collectively identified 18 key shared genes. Further, using two machine learning approaches, we ultimately identified 4 core hub genes (CDC42EP2, FKBP5, CD79A, and TDP1), which have great value in the diagnosis of RA and MG and are closely related to immune cell infiltration.</p><p><strong>Conclusion: </strong>Our study has unveiled the bidirectional causality between RA and MG, and identified shared molecular characteristics, highlighting the potential for developing targeted therapeutic strategies. Key Points • Our study shows a significant link between RA and increased MG risk, suggesting a bidirectional causal relationship. • We identified 18 key shared genes between RA and MG through differential expression and WGCNA, and pinpointed 4 core hub genes (CDC42EP2, FKBP5, CD79A, TDP1) using several machine learning algorithms. These genes are valuable for diagnosis and associated with immune cell infiltration. • We developed a diagnostic nomogram based on the hub genes, which could aid in diagnosing and predicting RA and MG, guiding clinical practice and personalized medicine.</p>","PeriodicalId":10482,"journal":{"name":"Clinical Rheumatology","volume":" ","pages":"3399-3417"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Clinical RheumatologyPub Date : 2025-09-01Epub Date: 2025-07-19DOI: 10.1007/s10067-025-07577-8
Rachael Stovall, Dominique Feterman Jimenez, Jose Andres Porres Arnaez, Vishwesh Bharadiya, Jean W Liew, Alison M Bays, Jenna Thomason, Londyn Robinson, Rashmi Dhital, Namrata Singh
{"title":"Patient characteristics and outcomes of emergency visits in psoriatic arthritis: results from the U.S. Nationwide Emergency Department Sample.","authors":"Rachael Stovall, Dominique Feterman Jimenez, Jose Andres Porres Arnaez, Vishwesh Bharadiya, Jean W Liew, Alison M Bays, Jenna Thomason, Londyn Robinson, Rashmi Dhital, Namrata Singh","doi":"10.1007/s10067-025-07577-8","DOIUrl":"10.1007/s10067-025-07577-8","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate patient characteristics and outcomes associated with emergency department (ED) visits in psoriatic arthritis (PsA) using the Nationwide Emergency Department Sample (NEDS), the largest all-payer U.S. ED database.</p><p><strong>Methods: </strong>We analyzed 2019 NEDS data for adults aged ≥ 18 years with and without PsA per International Classification of Diseases (ICD) codes. Baseline demographics, clinical comorbidities, and primary ED diagnoses were compared between PsA and non-PsA ED visits cross-sectionally. We assessed the top three primary diagnoses associated with inpatient admission among PsA ED visits. Pearson chi squared tests were used to compare categorical variables and t-tests to compare continuous variables. Multivariable logistic regression was used to identify factors associated with inpatient admission.</p><p><strong>Results: </strong>Among 117,359,429 ED visits, 61,079 (0.05%) involved PsA patients (mean age 58.9 ± 15.2 years, 59.6% female, 84.2% non-Hispanic White, 47.4% Medicare-insured). Compared to non-PsA visits, PsA visits involved older patients, higher Medicare usage (30.1% vs. 47.4%), and a greater admission frequency (54.6% vs. 17.0%). Top diagnoses linked to admission in PsA patients were septicemia, skin and subcutaneous infections, and heart failure. Factors increasing the odds of admission included older age (OR 1.02, 95% CI 1.02-1.03), alcohol use disorders (OR 3.43, CI 2.67-4.41), chronic kidney disease (OR 2.23, CI 1.89-2.64), obesity (OR 2.32, CI 2.05-2.64), and stroke (OR 4.83, CI 3.02-7.72).</p><p><strong>Conclusion: </strong>PsA ED visits were characterized by older, non-Hispanic White patients, with over half requiring admission. Differences in age and comorbidity burden between patients with and without PsA may explain some of the findings. Key Points • We used a large U.S. database to assess ED utilization and outcomes in PsA patients. • Older age, comorbidities, and socioeconomic factors influence inpatient admission odds in patients with PsA. • Findings highlight health disparities, emphasizing the need for interventions to improve PsA patient outcomes.</p>","PeriodicalId":10482,"journal":{"name":"Clinical Rheumatology","volume":" ","pages":"3573-3579"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12342128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Clinical RheumatologyPub Date : 2025-09-01Epub Date: 2025-07-19DOI: 10.1007/s10067-025-07579-6
Burak Oz, Yusuf Dogan, Ahmet Karatas, Suleyman Serdar Koca
{"title":"Radiological and serological predictors of cavitary transformation in rheumatoid arthritis-associated pulmonary nodules: a retrospective cohort study.","authors":"Burak Oz, Yusuf Dogan, Ahmet Karatas, Suleyman Serdar Koca","doi":"10.1007/s10067-025-07579-6","DOIUrl":"10.1007/s10067-025-07579-6","url":null,"abstract":"<p><strong>Background/objectives: </strong>Cavitary pulmonary nodules (CPN) represent a rare but clinically relevant manifestation of rheumatoid arthritis (RA), yet their radiological and serological predictors remain poorly defined. This study aimed to identify key clinical, immunological, and imaging features associated with CPN among RA patients presenting with pulmonary nodules (PN).</p><p><strong>Methods: </strong>This retrospective cohort included 156 RA patients with PN identified on thoracic computed tomography between 2010 and 2024. Clinical data, autoantibody status, treatment characteristics, and radiological parameters were compared between patients with and without CPN.</p><p><strong>Results: </strong>CPN were detected in 9.0% (n = 14) of cases. Compared to patients without CPN, affected individuals had a significantly greater number of nodules, larger nodule diameters, and higher seropositivity for rheumatoid factor, anti-cyclic citrullinated peptide antibodies, and ANCA. The largest nodule diameter was the only independent predictor of cavitary transformation (OR: 1.59, 95% CI: 1.19-2.12; p = 0.002), with stronger effect sizes in penalized regression (OR: 6.69 per SD; 95% CI: 3.52-12.61). Despite limited sample size, ROC analysis identified an optimal cut-off of 18 mm, yielding excellent discriminative performance (AUC: 0.979; sensitivity: 92.9%, specificity: 95.8%), further supported by bootstrap validation. No significant differences in baseline treatments were observed, though greater variability in drug exposure and post-diagnostic therapy adjustments was noted in CPN-positive patients.</p><p><strong>Conclusions: </strong>Radiological morphology-particularly increased nodule size-alongside autoantibody positivity, are key correlates of cavitary transformation in RA-associated PN. These findings support the use of imaging-based risk stratification and highlight the need for prospective validation across broader RA populations. Key Points • CPN were detected in 9% of RA patients with PN on CT imaging • Larger PN diameter emerged as the principal independent predictor of cavitary transformation, with an18 mm cut-off providing high discriminative capacity (AUC = 0.979). • Seropositivity for RF, anti-CCP, and ANCA IFA was significantly associated with cavitation. • Greater heterogeneity in pre-diagnostic leflunomide exposure and more frequent post-diagnostictherapy modifications among CPN-positive patients suggest a dynamic and potentially treatmentinfluenceddisease pattern, possibly reflecting variability in therapeutic response over time.</p>","PeriodicalId":10482,"journal":{"name":"Clinical Rheumatology","volume":" ","pages":"3433-3444"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"CD68 + macrophage infiltrations in muscle tissue of juvenile dermatomyositis associated with the course of the disease, not with the severity.","authors":"Yun Zhou, Fei Zheng, Yini Wang, Weizhong Gu, Yiping Xu, Liping Teng, Qian Ma, Bin Hu, Meiping Lu, Xuefeng Xu","doi":"10.1007/s10067-025-07601-x","DOIUrl":"10.1007/s10067-025-07601-x","url":null,"abstract":"<p><strong>Objective: </strong>To explore the relationship between the immunohistochemical characteristics of muscle tissue and clinical phenotype, and investigate the influencing factors of inflammatory cell infiltrations in muscle tissue in Juvenile dermatomyositis (JDM) patients.</p><p><strong>Methods: </strong>Nineteen JDM patients and five control patients were included in the present study. Immunohistochemical staining was performed on the muscle biopsies.</p><p><strong>Results: </strong>The macrophages and lymphocytes significantly increased in muscle tissue of JDM patients compared with the control group. The positive area proportions of macrophage infiltrations and T lymphocyte infiltrations in muscle tissue of JDM were linearly correlated (CD68 and CD3 r = 0.592, p < 0.001; CD68 and CD4 r = 0.690, p < 0.001; CD68 and CD8 r = 0.579, p < 0.001; CD163 and CD3 r = 0.649, p < 0.001; CD163 and CD4 r = 0.651, p < 0.001; CD163 and CD8 r = 0.763, p < 0.001). In JDM patients with a disease course < 1 year, the duration of disease is linearly correlated with the degree of CD68 + macrophage infiltrations in muscle tissue, and the longer the disease duration, the more CD68 + macrophage infiltrations in the muscle tissue (r = 0.283, p = 0.028). The positive area proportions of CD68 + macrophages and T lymphocytes (CD3 + , CD4 + , and CD8 +) infiltrating the muscle tissue of anti-PM/Scl75-positive JDM patients were significantly higher than those of anti-PM/Scl75-negative patients. The degree of T lymphocyte (CD3 + , CD4 + , and CD8 +) infiltrations in the muscle tissue of anti-NXP2-positive JDM patients was significantly lower than those of anti-NXP2-negative patients.</p><p><strong>Conclusion: </strong>The CD68 + macrophages infiltrations of muscle tissues in JDM associated with the course of JDM, not related to disease severity. Key Points • The inflammatory cell infiltrations of muscle tissues associated with the course of JDM, not severity. • Macrophage infiltrations in muscle tissue of JDM are linearly correlated with T lymphocyte infiltrations. • The duration of disease is linearly correlated with CD68 + macrophage infiltrations in muscle tissue.</p>","PeriodicalId":10482,"journal":{"name":"Clinical Rheumatology","volume":" ","pages":"3629-3638"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Synovial infiltrating immune cell heterogeneity associated with synovitis severity and systemic disease activity in rheumatoid arthritis: a cross-sectional study.","authors":"Peishi Rao, Shanzhao Jin, Baozhen Zhang, Ru Li, Xiaolin Sun, Liang Zhang, Zhanguo Li","doi":"10.1007/s10067-025-07565-y","DOIUrl":"10.1007/s10067-025-07565-y","url":null,"abstract":"<p><strong>Background: </strong>Rheumatoid arthritis (RA) is a systemic autoimmune disorder characterized by persistent synovitis. The synovial inflammation observed in RA exhibits significant heterogeneity among patients.</p><p><strong>Objective: </strong>To examine the relationship between major immune cell infiltration profiles in synovium and both local synovitis and systemic manifestations of RA.</p><p><strong>Methods: </strong>This cross-sectional study enrolled 22 RA patients (mean disease duration: 7.1 years). Synovial biopsies were assessed using the Krenn synovitis scoring system (no/low/high-grade) and immunohistochemical pathotyping (lympho-myeloid, diffuse-myeloid, pauci-immune). Clinical parameters, including the Disease Activity Score-28 (DAS28), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and autoantibody status, were systematically analyzed.</p><p><strong>Results: </strong>Immunohistochemical analysis identified three distinct synovial pathotypes, characterized by specific distributions of CD3⁺ T cells, CD68⁺ macrophages, CD20⁺ B cells, and CD138⁺ plasma cells. Synovitis severity, classified using the Krenn scoring system, demonstrated significant differences in synovial inflammation and stromal hyperplasia. High-grade synovitis exhibited significantly increased infiltration of CD20⁺ B cells (p = 0.025) and CD138⁺ plasma cells (p = 0.034) compared to non-inflamed tissues. Pathotype distribution analysis revealed a predominance of the pauci-immune subtype in the no-synovitis group (59.1%), whereas the lympho-myeloid subtype became progressively more prevalent with increasing synovitis severity (31.8% overall).ESR, CRP, and DAS28, were significantly correlated with synovial immune cell infiltration and synovitis severity, whereas no significant association was observed between synovitis and RA associated autoantibodies such as anti-cyclic citrullinated peptide (anti-CCP) or rheumatoid factor (RF).</p><p><strong>Conclusion: </strong>These findings underscore the complex interactions between synovial infiltrating immune cells, synovitis severity, and systemic disease activity, providing valuable insights for the development of personalized RA management strategies. Key Points •This study characterizes synovial immune infiltrates in relation to synovitis severity and systemic disease activity in RA •High-grade synovitis, as assessed by the Krenn scoring system, is associated with increased infiltration of immune cells, such as CD20⁺ B cells and CD138⁺ plasma cells, contributing to more severe inflammation and joint destruction. •The distribution of synovial pathotypes (lympho-myeloid, diffuse-myeloid, pauci-immune) correlates with synovitis severity, providing insights into potential molecular subtypes that could influence clinical phenotypes and treatment responses in RA.</p>","PeriodicalId":10482,"journal":{"name":"Clinical Rheumatology","volume":" ","pages":"3487-3495"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Clinical RheumatologyPub Date : 2025-09-01Epub Date: 2025-07-15DOI: 10.1007/s10067-025-07549-y
Dianshan Ke, Rongsheng Zhang, Hanhao Dai, Yibin Su, Linhai Yang, Dong Guo, Jie Xu
{"title":"Single-cell immunomics reveals the immunological hallmarks about the onset and different outcomes for ankylosing spondylitis patients.","authors":"Dianshan Ke, Rongsheng Zhang, Hanhao Dai, Yibin Su, Linhai Yang, Dong Guo, Jie Xu","doi":"10.1007/s10067-025-07549-y","DOIUrl":"10.1007/s10067-025-07549-y","url":null,"abstract":"<p><strong>Objectives: </strong>The immunological hallmarks associated with ankylosing spondylitis (AS) occurrence and development were unclear.</p><p><strong>Method: </strong>After recruiting healthy donors and patients in different stages, we performed single-cell RNA sequencing for peripheral blood mononuclear cells (PBMCs) and relied on T-cell receptor (TCR) and B-cell receptor (BCR) analyses to explore the immunological patterns causing AS onset and different outcomes.</p><p><strong>Results: </strong>Effector T/B cells possessed marked clonal expansion and AS lesions were characterized by B-cell clonal expansion. However, patients in remission showed weak T/B-cell clonal expansion. The usage of top 10 CDR3 sequences and the rearrangement of V(D)J genes in AS remission was less diverse. BCR-V(D)J rearrangement in healthy donors was more specific. AS different stages all exhibited preferred TRA genes (TRAV17 for onset, TRAV9-2 for aggravation, and TRAV23/DV6 and TRAJ56 for remission) and TRBV12-5 was overrepresented in remission. The top two paired TCR-V/J genes for AS different stages were all different (TRBV20-1/TRBJ2-1 and TRAV14/DV4/TRAJ53 for onset, TRBV7-9/TRBJ2-5 and TRBV20-1/TRBJ2-3 for aggravation, and TRBV27/TRBJ2-1 and TRBV28/TRBJ2-1 for remission). IGHV3-30 and IGHV4-30-2 were overrepresented in remission and the top two paired BCR-V/J genes for AS different stages were also different (IGHV3-23/IGHJ4 and IGHV3-7/IGHJ3 for onset, IGLV1-44/IGLJ2 and IGHV3-7/IGHJ4 for aggravation, and IGHV3-74/IGHJ4 and IGLV3-1/IGLJ2 for remission).</p><p><strong>Conclusion: </strong>These findings provide insights into the dynamic immune-response features of AS onset and outcomes, suggesting that there is an important connection between driving AS lesions and B-cell clonal expansion, and decreased V(D)J usage diversity in remission has guiding value for inducing rapid remission in AS patients. Key Points • Differential immunodominant epitopes in T/B-cell responses are associated with AS onset and different outcomes. • The specificity of BCR-V(D)J in AS patients determines the driving effect of B-cell clonal expansion on AS lesions. • Decreased V(D)J-usage diversity in remission results in the contribution of inadequate clonal expansion to AS remission.</p>","PeriodicalId":10482,"journal":{"name":"Clinical Rheumatology","volume":" ","pages":"3549-3559"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}