Lupus retinopathy (LR) is a sight-threatening complication of systemic lupus erythematosus (SLE), yet disease-specific serologic biomarkers are lacking. Previous studies have shown that anti-recoverin (RCV) antibodies act as a biomarker of cancer-associated retinopathy and serum level of anti-RCV antibodies was elevated in SLE patients with fundus abnormalities. This study screened three candidate epitopes of RCV protein and evaluated anti-RCV epitope-specific autoantibodies as candidate serological markers for LR. The epitopes of RCV protein were predicted by DNAStar software and cross-checked by BepiPred-2.0 and ABCpred. Serum autoantibodies against RCV and three linear epitopes (RCV55–70, RCV139–154, RCV155–170) was determined by ELISA in SLE patients with LR (n = 48), without LR (non-LR, n = 48), and healthy controls (HC, n = 44). Statistical analyses included the Kruskal–Wallis with Dunn’s post-hoc tests, Mann-Whitney U test, Student’s t test, Chi-Square or Fisher’s exact tests, correlation analysis, logistic regression, and ROC analysis. Epitope-specific anti-RCV antibodies were significantly higher in LR than in non-LR SLE and HC (all p < 0.05). Anti-RCV139–154 demonstrated the highest diagnostic performance for identifying LR from SLE, with an AUC of 0.808 (95% CI: 0.721–0.895), a sensitivity of 54.2% and a specificity of 93.8%, outperforming full-length anti-RCV. Furthermore, anti-RCV139–154 levels positively correlated with SLE disease activity (SLEDAI, r = 0.430, p < 0.001), anti-dsDNA titers, and IgG levels, and inversely correlated with C3 and C4 levels (p < 0.001). Notably, anti-RCV139–154 levels were preferentially elevated in microvasculopathic LR and declined after treatment. Epitope-specific anti-RCV antibodies, especially anti-RCV139–154, may serve as novel biomarkers for early identification of LR in SLE patients.

Glucocorticoids (GC) comprise a cornerstone in the treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV); however, prolonged GC exposure leads to substantial toxicity and immune system-related complications. Hence, identifying treatment strategies that enable early GC withdrawal while maintaining disease control is of clinical importance. To investigate the proportion and characteristics of patients achieving GC-free clinical remission (GFCR) 48 weeks after treatment initiation in patients with newly diagnosed microscopic polyangiitis (MPA) or granulomatosis with polyangiitis (GPA) and examine their long-term clinical outcomes (up to week 96). We conducted a retrospective cohort study using clinical data from a multicenter, nationwide registry in Japan comprising patients with newly diagnosed MPA or GPA and at least 48 weeks of follow-up. GFCR was defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 with complete GC withdrawal. Univariable and multivariable logistic regression analyses were used to identify independent predictors of GFCR at week 48, and a sensitivity analysis using a matched cohort was performed to validate robustness. A total of 728 patients were enrolled in the registry, of whom 544 were followed for ≥ 48 weeks; among them, 29 (5.3%) achieved GFCR at week 48. Use of rituximab (RTX) for induction therapy and avacopan within 48 weeks were independently associated with achieving GFCR (multivariable analysis, model 1: RTX: odds ratio [OR]: 3.9, 95% confidence interval [CI]: 1.5–10.0; avacopan: OR: 24.3, 95% CI: 5.8–101.9; both p < 0.01). Conversely, methylprednisolone pulse therapy was associated with a lower likelihood of achieving GFCR (multivariable analysis, model 1: OR: 0.08, 95% CI: 0.02–0.44; p < 0.01). Patient’s demographic and baseline disease characteristics were not predictive of GFCR. In the long-term (weeks 48 through 96), the rates of death, relapse, and serious infection were similar regardless of GFCR status at week 48. The use of RTX for induction therapy and avacopan within 48 weeks is independently associated with achieving GFCR at week 48 in patients with MPA and GPA, supporting their potential as key components of GC-sparing strategies in AAV. Prospective studies are needed to confirm these results and optimize treatment algorithms to ensure disease control and minimize GC-related toxicity.

Antimitochondrial antibodies (AMA), the hallmark of primary biliary cholangitis (PBC), have been inconsistently reported and poorly characterized in systemic sclerosis (SSc). Although recently linked to subclinical dysmotility in a cohort enriched for gastrointestinal (GI) involvement, data on the prevalence and clinical relevance of AMA in real-life SSc cohorts remain limited. A retrospective cross-sectional study was conducted on consecutive SSc patients followed at a referral center for the disease. Patients were tested for serum AMA according to reference standards, including HEp-2 immunofluorescent screening and ELISA confirmation (anti-E2 pyruvate dehydrogenase). Patients’ features were compared between AMA-positive and -negative cases. Among 165 SSc patients (20% diffuse cutaneous disease, 33% interstitial lung disease, 7.3% pulmonary arterial hypertension; 51% positive for anticentromere antibodies, 29% anti-topoisomerase I, 12% anti-RNA polymerase III), 37 (22%) were AMA-positive. While strongly associated with PBC, AMA were not linked to significant differences in cutaneous, vascular, pulmonary, or myocardial involvement. However, AMA were associated with GI vascular involvement (OR 13.3, 95% CI 2.53–95.0; p = 0.002), including gastric antral vascular ectasia (OR 7.99, 95% CI 1.05–72.5; p = 0.045), independently from PBC or symptoms of SSc-GI involvement. These complications are clinically relevant, as they may lead to GI bleeding and refractory iron-deficiency anemia. In our cohort of SSc patients systematically screened for autoantibodies, we found a high prevalence of AMA and identified a novel putative association with GI vascular involvement, which warrants confirmation in independent studies.

Conventional therapeutic interventions for rheumatoid arthritis (RA) are frequently induced immunosuppressive side effects. The present study explores the therapeutic potential of Cyclovirobuxine D (CycD), a triterpenoid alkaloid isolated from Buxus microphylla, in a collagen-induced arthritis (CIA) mouse model or in vitro. The CIA model was treated with varying doses of CycD or methotrexate. The biomarkers of inflammatory factors related to macrophage polarization and oxidative stress in serum or synovial tissue was conducted. The RNA sequencing (RNA-seq) was employed to identify key post-regulatory genes in CycD treatment. The pathway was investigated using PI3K activators and inhibitors, both in vivo and vitro. Molecular docking, Network Pharmacology, Drug Affinity Responsive Target Stability (DARTS) and Cellular Thermal Shift Assay (CETSA) were performed to validate. The administration of CycD resulted in a substantial alleviation arthritis severity, joint pathology, and levels of biomarkers associated with macrophage polarization and oxidative stress in CIA mice. In contrast to methotrexate, CycD exhibited minimal adverse effects on the spleen and thymus. RNA-seq and immunofluorescent staining has showed that the biological function of CycD is predominantly characterized by its capacity to suppress the PI3K-AKT pathway in M1 macrophages. The activation of PI3K was found to counteract the therapeutic benefits of CycD in both CIA mice, RAW264.7 and THP-1 cells. Molecular docking, Network Pharmacology, DARTS and CETSA confirmed that CycD competes with PI3K for binding in M1-type macrophages. CycD alleviates collagen-induced arthritis by inhibiting the PI3K-AKT pathway in macrophages.

In chronic diseases the length and redundancy of medical records can hamper the accurate interpretation of the individual clinical history, and we hypothesize that Natural Language Processing (NLP) may be used to optimize information from unstructured texts in electronic health records (EHRs). We developed an NLP-based classifier to discriminate rheumatoid (RA) and psoriatic arthritis (PsA) versus non-inflammatory rheumatic diseases (NIRD), namely osteoarthritis and fibromyalgia, from notes in the rheumatology practice. A retrospective cross-sectional study was conducted on 1,372 anonymized EHRs from a single Italian rheumatology center, including 468 RA, 732 PsA, and 172 NIRD cases. After removing explicit diagnostic referrals, texts were embedded using five models and the resulting embeddings were used to train multiple classifiers. The best-performing embedding-classifier combination was selected, predictions were stratified into high-, moderate-, and low-certainty according to a confidence-based decision system, and explainability was assessed using LIME and SHAP. The chosen model reached an overall accuracy of 85% in distinguishing between the three diagnostic groups. In detail, 74.5% of cases were classified with high certainty, reaching 94.6% accuracy, while only 1.5% were considered uncertain. No misclassifications occurred between RA and NIRD, though some overlap was seen between PsA and the other two conditions. Attempts to interpret the model’s decisions through dedicated algorithms provided partially meaningful insights, but results were inconsistent, especially when the clinical notes included complex or negated language. We developed an NLP-based classifier to detect inflammatory arthritis from unstructured rheumatology notes. The model showed high confidence and accuracy, with low risk of missing patients with inflammatory disease. Although interpretability remains a limitation, external validation in multicenter and multilingual cohorts is warranted to confirm its generalizability.

BackgroundPatients with rheumatoid arthritis (RA) are at a higher risk for sarcopenia than the general population. Exercise therapy can improve muscle strength in older adults; however, its efficacy in older patients with RA has not been fully established. This study aimed to evaluate the efficacy of a personalized exercise program on physical function in older patients with RA at high risk for sarcopenia.MethodsA single-centre, parallel-group, two-arm, superiority randomized controlled trial was conducted in patients with RA aged 60–85 years who were at risk of sarcopenia. The intervention group (n = 69) underwent a 16-week personalized exercise program in addition to nutritional guidance and standard care, whereas the control group (n = 65) received only nutritional guidance and standard care. The primary outcome was the change in the total Short Physical Performance Battery (SPPB) scores from baseline to week 16.ResultsA total of 140 patients were randomized. Of these, 134 initiated the assigned intervention. There was a 0.2-point difference in SPPB total score from baseline to week 16 between the intervention group (+ 0.4 points) and the control group (+ 0.2 points); 95% confidence interval: -0.1 to 0.5; p = 0.206. Regarding the secondary outcomes at week 16, there was a tendency for improvement in the chair-stand test, grip strength, and the mental component score.ConclusionThe 16-week personalized exercise therapy did not improve the total SPPB scores. However, the intervention may improve standing ability, grip strength, and mental health-related quality of life in older patients with RA at high risk of sarcopenia.Trial registrationThis study was registered with UMINCTR (trial number: UMIN000044930).Supplementary InformationThe online version contains supplementary material available at 10.1186/s13075-026-03751-8.