ABSTRACT Rheumatoid arthritis (RA) remains a challenging autoimmune disease with variable treatment responses to tumor necrosis factor‐α (TNF‐α) inhibitors. This study investigates the clinical significance of PD‐1hiCXCR5−CD4+T peripheral helper (Tph) cells in RA and their potential utility as biomarkers for predicting etanercept (ETN) therapy response. We enrolled 58 RA patients, 12 age‐ and sex‐matched osteoarthritis patients, and 15 healthy controls, with Tph cells quantified by flow cytometry. Among 25 RA patients with inadequate response to conventional synthetic disease‐modifying antirheumatic drugs receiving ETN therapy, treatment outcomes were stratified by ACR20 response criteria. Tph cell frequency was significantly elevated in RA patients and correlated positively with multiple disease activity indicators. At baseline, ETN nonresponders exhibited higher Tph proportions than responders (13.23 ± 2.60% vs. 10.82 ± 3.08%, p = 0.0467). Following ETN treatment, responders demonstrated significant Tph reduction (10.82% decreased to 7.97%, p = 0.0105), paralleling serum IL‑21 dynamics. In an exploratory analysis, baseline Tph levels showed an association with ETN response. These findings suggest that circulating Tph cells may serve as a candidate biomarker for RA disease activity and therapeutic response monitoring, warranting further validation in larger prospective cohorts.

Background: Atopic dermatitis (AD) and asthma are common type 2 inflammatory diseases linked by the atopic march. In adults with AD, the prevalence of comorbid asthma and the strength of the AD–asthma association remain uncertain, with marked heterogeneity across studies. Moreover, the role of modern systemic therapies in this comorbidity is increasingly debated. Objective: To estimate the global pooled prevalence of asthma in adults with AD, quantify the AD–asthma association, and discuss the potential impact of targeted therapies (dupilumab, abrocitinib, omalizumab) on asthma comorbidity. Methods: Systematic review and random-effects meta-analysis (ID CRD420261304804) of observational studies from PubMed, EMBASE, and Cochrane Library (inception to 19 January 2026). Pooled prevalence and odds ratios (ORs) were calculated, with subgroup analyses by region, ethnicity, and disease definition. Results: Seventy-five studies were included. The global pooled prevalence of asthma in adults with AD was 25.9% (95% CI 22.1–30.0%; I2 = 99.9%). AD was significantly associated with asthma (OR 3.64, 95% CI 2.89–4.57; I2 = 98.6%). Prevalence varied from 9.3% in Asia to 63.2% in South America. Although dupilumab and other targeted agents are effective in both diseases, isolated reports of new-onset asthma after treatment were identified; these cases more likely reflect the natural progression of AD or unmasking of pre-existing asthma than a direct adverse drug reaction. Conclusions: Asthma is highly prevalent in adults with AD and is strongly associated with AD. Geographic and ethnic disparities call for stratified screening. Clinicians should be aware that new-onset respiratory symptoms during targeted therapy may represent AD-related comorbidity rather than drug-induced asthma.

OBJECTIVES:Previous studies have identified unique challenges for RA patients of different genders, which impact disease management. However, the association between disease activity and health-care-seeking behaviours in male and female RA patients remains underexplored. This study aimed to investigate this association, with a specific focus on the gender-specific effects of follow-up intervals on disease control. METHODS:A nationwide survey (July-September 2023) across 330 rheumatology centres in China included 13 278 female (83.85%) and 2557 male RA patients (16.15%) aged ≥18 years. Standardized questionnaires captured demographic and health-care-seeking behaviours. Disease activity was assessed using the Clinical Disease Activity Index (CDAI). RESULTS:Females had younger disease onset (45.84 vs 51.03 years, P < 0.001), longer disease duration (7.51 vs 5.64 years, P < 0.001), higher low disease activity/clinical remission rates (22.61% vs 15.33%, P < 0.001), and lower glucocorticoid use (39.5% vs 47.73%, P < 0.001). Despite similar self-reported regular follow-up rates (84.73% vs 83.14%), both genders experienced suboptimal visit intervals (>3 months: 61.30% vs 62.65%, P < 0.001). Prolonged follow-up intervals were independently associated with poor disease control (CDAI > 10) in the female subgroup, with longer intervals linked to higher odds of inadequate control at 6-month [odds ratio (OR) = 1.22, 95% CI: 1.09-1.37, P < 0.001] and 12-month intervals (OR = 1.43, 95% CI: 1.22-1.60, P < 0.001). Regular monitoring reduced high disease activity risk across genders (OR = 0.64, 95% CI: 0.56-0.74, P < 0.001). A generalized linear model showed no significant follow-up interval - gender interaction on disease activity (all P > 0.20). CONCLUSION:This large-scale study revealed gender-dimorphic patterns in RA progression and health-care engagement. Females tended to exhibit better treatment response, with a more pronounced interval-dependent disease control trend. No significant interval-gender interaction confirmed this was a descriptive trend, not a validated gender-specific difference. Our findings emphasize the need for strategies accounting for such gender-dimorphic trends to optimize care continuity and improve RA management.

OBJECTIVES:This study aimed to investigate the gender-specific factors influencing health-related quality of life (HRQoL) among rheumatoid arthritis (RA) patients within biopsychosocial framework and the interacting effects of these factors. METHODS:A prospective multi-centre cross-sectional study was conducted. Binary logistic regression and subsequent stratified analyses were used to analyse the determinants of HRQoL among RA patients and how they interacted. RESULTS:Female patients (83.85%) exhibited earlier onset (45.68 vs. 50.85 years), longer disease duration (60.00 vs. 36.00 months), lower Clinical Disease Activity Index (CDAI) (19.00 vs. 22.00), and less glucocorticoid use (39.55% vs. 47.75%). Multivariable analysis suggested that better HRQoL was linked to urban residence and higher education. Worse HRQoL was related to older age at onset, higher financial burden, glucocorticoid use, elevated CDAI, irregular follow up, longer follow-up intervals, comorbidities, anxiety/depressive symptoms, poor sleep satisfaction, and fatigue. Stratified analysis revealed significant interactions among CDAI and financial burden, anxiety/depressive symptoms and sleep satisfaction. CONCLUSIONS:These findings highlight the biopsychosocial factors affecting HRQoL, emphasising the need for gender-specific strategies and targeted interventions focusing on financial burden, anxiety/depressive symptoms and sleep satisfaction in RA patients with moderate-to-high disease activity.

OBJECTIVE:Despite growing interest in the gut microbiota and blood metabolome in patients with ankylosing spondylitis (AS), its role remains poorly understood. Here, we investigate how microbial and metabolic alterations contribute to AS. METHODS:Fecal microbiome data from 40 AS patients were compared with those from 40 healthy controls (HCs) using 16S ribosomal RNA (rRNA) gene sequencing. The plasma metabolic profiles were analyzed and integrated with the microbiota data to identify biological characteristics specific to AS. RESULTS:AS patients showed significant enrichment of specific genera, including Megamonas, Elusimicrobium, Dysgonomonas, Ruminococcus_gauvreauii_group, and unclassified_Prevotellaceae. Pathways with the most differentially expressed metabolites included bile secretion; neomycin, kanamycin, and gentamicin biosynthesis; and arachidonic acid metabolism. Positive correlations between Megamonas and Elusimicrobium and metabolites such as piribedil, l-cystathionine, and crocetin dialdehyde suggested microbial enrichment in AS patients. CONCLUSIONS:A disrupted gut microbiota and altered metabolites are present in AS patients. Integrating microbiome and metabolomic data reveals significant disruptions in AS patients, improving our understanding of its pathogenesis.

OBJECTIVES:To assess the clinical significance of Mer receptor tyrosine kinase (MerTK) on circulating natural killer (NK) cells in systemic lupus erythematosus (SLE). METHODS:63 patients with SLE and 36 healthy controls (HCs) were recruited in this study. Peripheral blood samples were collected from all participants. MerTK expression on circulating NK cells (CD3-CD56+) was detected by flow cytometry. MerTK expression was compared between patients with SLE and HCs or lupus nephritis (LN) and non-LN subgroups, and its correlation with clinical or laboratory features was also investigated. Bioinformatic analysis was conducted to explore the potential function of MERTK in NK cells in SLE. RESULTS:MerTK expression on circulating NK cells was significantly higher in patients with SLE than that in HCs. In patients with SLE, NK-cell specific MerTK expression was positively correlated with Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), anti-double-stranded DNA antibody levels, proportions and absolute count of B lymphocytes, but negatively correlated with complement C3, complement C4, proportions and absolute count of NK cells. Moreover, NK-cell specific MerTK expression was significantly higher in the LN group than that in the non-LN group. Bioinformatics analysis revealed that MERTK was one of the dysregulated NK-cell related genes in SLE, and the differentially expressed genes related to MERTK were associated with biological pathways including NK cell activation and response to type I interferon (IFN-I). In vitro study showed that MerTK expression on NK cells was increased after IFN-I treatment. CONCLUSIONS:The expression of MerTK on circulating NK cells was significantly elevated in patients with SLE, particularly in patients with LN, and was correlated with disease activity and autoantibody titres. MERTK expression may be related to regulation of NK cell activation and induced by IFN-I in SLE. Our findings indicate that circulating NK-cell specific expression of MerTK may play a role in the development and progression of SLE.

BACKGROUND:Macrophages play a crucial role in SLE associated diffuse alveolar hemorrhage (DAH), and Axl receptor tyrosine kinase (AxlTK) is prominently expressed in macrophages. This study aimed to evaluate the role of AxlTK in the onset of lupus-associated DAH. METHODS:The expression of soluble Axl (sAxl) in serum from SLE patients with/without DAH was detected by ELISA. Wild-type (WT) and AxlTK-Knockout (Axl-KO) mice were used to explore the role of AxlTK in the development of DAH in a pristane-induced lupus model, and the therapeutic effect of AxlTK inhibitor TP-0903 was also assessed. The effect of AxlTK on macrophage function was demonstrated by flow cytometry and ELISA. The macrophages from the lung tissues of WT and Axl-KO DAH mice were collected for RNA-sequencing to further explore the mechanism. RESULTS:The serum sAxl level was higher in SLE patients with DAH, and correlated with disease activity. And AxlTK was highly expressed on macrophages from the lungs of DAH mice. Compared with WT mice, both Axl-KO mice and TP-0903-treated mice exhibited less severe DAH, with reduced iNOS+F4/80+ macrophages and elevated CD206+F4/80+ macrophages in lung tissues. Further experiments revealed that AxlTK deficiency inhibited the polarization of bone marrow-derived macrophages (BMDMs) and decreased the uptake of apoptotic cells. Additionally, RNA-sequencing analysis revealed that AxlTK may affect macrophage activation in DAH mice through inflammatory pathways. CONCLUSION:AxlTK is involved in the development of DAH by regulating the activation of macrophages and might be a potential therapeutic target for SLE with DAH.

Rheumatoid arthritis(RA)is a common immune-mediated inflammatory disease characterized by synovial inflammation and joint destruction,(1)affecting 0.5％to 1％of the global population and leading to disability.(2)Current therapies,including conventional synthetic disease-modifying antirheumatic drugs(csDMARDs),biologic DMARDs(bDMARDs),and targeted synthetic DMARDs(tsDMARDs),often limited by side effects,high costs,and incomplete efficacy.

Cell metabolism is an indispensable biochemical process that provides the basic energy and materials necessary for normal cell function. Accumulating evidence implicates abnormal metabolism of T cells as playing a critical role in the pathogenesis of rheumatoid arthritis (RA). The deacetylase SIRT3 has been shown to directly regulate energy metabolism in nonimmune cells. However, the role of SIRT3 in T cells and whether it participates in RA process remain unclear. In this study, we demonstrated that T-cell glycolysis was inhibited after SIRT3 deficiency. Compared to wild-type mice, SIRT3 knockout mice exhibited more severe arthritis, cartilage erosion, and inflammation after immunization with antigen-induced arthritis (AIA). It is interesting to note that SIRT3 deficiency reduced the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a regulatory and rate-limiting enzyme in glycolysis. Overexpression of PFKFB3 was shown to restore the impaired ATP production caused by SIRT3 deficiency in T cells, and protects T cells from apoptosis. In summary, SIRT3 plays an important role in the regulation of T-cell metabolism in the pathogenesis of RA. SIRT3 deficiency decreases glycolysis, reduces ATP production, induces apoptosis in CD4+ T cells, and further promotes AIA in mice.

A 56-year-old woman with 1-year recurrent fever, rash, joint swelling (acute exacerbation) was diagnosed with adult-onset Still disease (AOSD) per 1992 Yamaguchi criteria. She initially improved with methylprednisolone, tocilizumab, methotrexate, and iguratimod but relapsed after discontinuing methylprednisolone. Twenty-four hours after first Re Du Ning injection, she developed progressive rash (extensive polymorphic erythema, bullae, and >30% body surface epidermal detachment), high fever, organ impairment, and coagulopathy and was diagnosed with AOSD complicated by macrophage activation syndrome (2004 haemophagocytic lymphohistiocytosis guidelines), toxic epidermal necrolysis, myocardial injury, hepatic impairment, and disseminated intravascular coagulation. Treatment included dexamethasone, methylprednisolone, plasma exchange, cyclosporine, anakinra, ganciclovir, voriconazole, intravenous immunoglobulin, and supportive care, leading to marked improvement in lesions. This case highlights rare AOSD complications and anakinra’s efficacy.

Psoriatic arthritis (PsA) is a chronic and progressive inflammatory arthritis associated with psoriasis, mainly affecting the axial and peripheral joints, characterized by a wide range of complex phenotypes, significant heterogeneity, and a multifactorial etiology. To effectively address the distinct challenges in managing PsA, a pivotal emphasis is placed on clarifying the concept of refractory PsA. Here, we propose a distinction between refractory PsA, differentiating between difficult-to-treat PsA (D2T PsA) and Pseudo-D2T PsA. The former centers on the lack of efficacy of multiple disease-modifying anti-rheumatic drugs (DMARDs) and signs suggestive of active/progressive disease, while also considering the challenges posed by comorbidities. The latter focuses on misdiagnosis and mismanagement, detailing the difficulties caused by artificial factors, whether by clinicians or patients. Hoping the clarification of these distinctions will enable clinicians to manage patients with refractory PsA more effectively.

Systemic lupus erythematosus (SLE) is associated with a significant risk of atherosclerotic cardiovascular disease, especially in the development of premature atherosclerosis. Specific prediction models for premature atherosclerosis in SLE patients are still limited. The objective of this study was to establish a predictive model for premature atherosclerosis in SLE. The study collected clinical and laboratory data from 148 SLE patients under the age of 55, between January 2021 and June 2023. The least absolute shrinkage and selection operator logistic regression model was utilized to identify potentially relevant features. Subsequently, a nomogram was developed using multivariable logistic analysis. The performance of the nomogram was evaluated through a receiver-operating characteristic curve, calibration curve, and decision curve analysis (DCA). A total of 148 SLE patients who fulfilled the inclusion criteria were enrolled in the study, of whom 53 patients (35.81

OBJECTIVE:This study aimed to classify idiopathic inflammatory myopathy (IIM) patients with cardiac involvement (IIM-CI) into different categories based on their clinical phenotypes via cluster analysis and to explore their differences in outcomes.METHODS:IIM-CI patients admitted to Peking Union Medical College Hospital from January 2015 to June 2021 were retrieved. The clinical data, laboratory examinations, and treatment were retrospectively reviewed, and the outcome was traced. A second-order clustering method was employed for categorization.RESULTS:A total of 88 IIM-CI patients were enrolled in this study and were classified into two categories through cluster analysis. Category I consisted of patients who exhibited distinct cardiac structural and functional changes, such as enlargement of atriums and/or ventricles, along with the remarkable heart insufficiency biomarkers, whereas patients of category II displayed more widely systemic injuries and intensive skeletal muscle weakness. In comparison, pulmonary hypertension (58.8% vs 16.7%, p < 0.01), arrhythmia (82.4% vs 27.8%, p < 0.01), and positive serum anti-mitochondrial-M2 antibody (52.9% vs 5.6%, p < 0.01) were more prevalent in category I than in category II, and serum N-terminal pro-B-type natriuretic peptide levels (1703.5 pg/L vs 364.0 pg/L, p = 0.02) were significantly elevated in category I, whereas skeletal muscle weakness (50.0% vs 74.1%, p = 0.02), interstitial lung disease (20.6% vs 63.0%, p < 0.01), skin rash (11.8% vs 48.1%, p < 0.01), arthralgia (2.9% vs 27.8%, p < 0.01), fever (2.9% vs 27.8%, p < 0.01), and dysphagia (2.9% vs 22.2%, p < 0.01) were more common in category II patients. Heart failure was the primary cause of death in category I, but severe pneumonia was predominantly responsible for deaths in category II.CONCLUSION:Two categories of IIM-CI were identified based on clinical features with distinctive characteristics. Two categories exhibited differences in clinical manifestations, autoantibody profiles, and the primary cause of death.

OBJECTIVE:Alterations in gut microbiota have been implicated in the pathogenesis of ankylosing spondylitis (AS), but the underlying mechanisms remain elusive. This study aims to investigate changes in gut microbiota and metabolites in individuals with AS before and after treatment with secukinumab, to identify the biological characteristics specific to AS patients and investigate the potential biomarkers, for optimizing therapeutic strategies more effectively. METHODS:Fecal microbiome data were collected from 30 AS patients before and after secukinumab therapy and compared with data from 40 healthy controls (HC). Additionally, we analyzed the metabolic profile of both groups from plasma. RESULTS:Findings indicated that the treatment-induced changes in the composition of several crucial bacterial groups, including Megamonas, Prevotella_9, Faecalibacterium, Roseburia, Bacteroides, and Agathobacter. Post-treatment, these groups exhibited a distribution more akin to that of the healthy populations compared with their pretreatment status. We identified three gut microbial taxa, namely Prevotellaceae_bacterium_Marseille_P2831, Prevotella_buccae, and Elusimicrobiota, as potential biomarkers for diagnosing individuals at a higher risk of developing AS and assessing disease outcomes. Plasma metabolomics analysis revealed 479 distinct metabolites and highlighted three disrupted metabolic pathways. Integration of microbiome and metabolomics datasets demonstrated a significant degree of correlation, underscoring the impact of the microbiome on metabolic activity. CONCLUSION:Secukinumab can restore the balance of the gut microbiome and metabolites in AS patients, rendering them more similar to those found in the healthy population. The analysis of microbiome and metabolomics data have unveiled some candidate biomarkers capable of evaluating treatment efficacy.