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PubMed2025

An Immunosenescent CD8+ T Cell Subset in Patients with Axial Spondyloarthritis and Psoriatic Arthritis Links Spontaneous Motility to Telomere Shortening and Dysfunction.

OBJECTIVE: A pathogenetic role of CD8+ T lymphocytes in radiographic axial spondyloarthritis (r-axSpA) and other spondyloarthritis (SpA) is sustained by genome-wide association studies and by the expansion of public T cell clonotypes in the target tissues. This study investigates the migration of CD8+ T cells along with their phenotype and functions in patients with r-axSpA and psoriatic arthritis (PsA). METHODS: Peripheral blood CD8+ and CD4+ T cells were isolated from patients with r-axSpA (n = 128), PsA (n = 60), and rheumatoid arthritis (RA) (n = 74) and healthy donors (HDs) (n = 79). Transwell migration assay was performed in the presence of different chemokines. CD8+ T cell immunoprofiling and effector functions were assessed by multiparametric flow cytometry. Transcriptome signature was evaluated by RNA sequencing analysis, whereas telomere length and dysfunction were measured by reverse transcriptase-polymerase chain reaction and immunofluorescence-fluorescence in situ hybridization, respectively. RESULTS: A significantly higher number of CD8+ T cells migrating in the absence of chemokine stimuli was found in patients with SpA compared with HDs and patients with RA. This subset, producing cytotoxic (granzyme B, perforin, granulysin) and proinflammatory molecules (tumor necrosis factor), was significantly enriched in terminally differentiated (CCR7-CD45RA+) and senescent (CD28-CD57+) cells having a gene expression profile characterized by cytolytic signature and natural killer markers. Remarkably, these spontaneously migrating CD8+ T cells showed DNA damage response activation, telomere shortening, and dysfunction. CONCLUSION: These data describe a terminally differentiated CD8+ T cell subset with a senescent and cytotoxic/proinflammatory profile and an intrinsic invasive potential enriched in patients with SpA that represents a possible player in disease pathogenesis.

Humans↗

PubMed2025

High prevalence and distinct patterns of metabolic syndrome in rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis: a population-based study.

INTRODUCTION: Metabolic syndrome (MetS) in inflammatory arthritis (IA) directly impacts its management and associated morbidity and mortality. MetS is a well-recognised comorbidity in PsA, but the epidemiology across IA is unclear. This study aimed to characterise the prevalence of MetS across rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) compared to controls. METHODS: We performed a cross-sectional analysis of half a million individuals from the UK Biobank, aged 40 to 69 years, who were collected between 2006 and 2010. Participants with RA, PsA, and axSpA were identified using ICD-10 codes and/or read codes. MetS was defined according to adapted National Cholesterol Education Program Adult Treatment Panel III criteria. Statistical analysis included ANOVA and chi-squared test for between-group difference and logistic regression for odds of MetS, adjusted for age, sex, CRP and smoking status. RESULTS: The prevalence of MetS was highest in RA (43.4%), followed by PsA (42.3%), axSpA (37.1%) and controls (31.8%). Hypertension was prevalent across all IAs (~ 80%), as was hypertriglyceridaemia. Elevated waist circumference and dysglycaemia were more prevalent in RA and PsA compared to axSpA. The adjusted odds of comorbid MetS were elevated in RA (OR 1.15; 95% CI 1.07, 1.24; p < 0.001) and PsA (OR 1.31; 95% CI 1.13, 1.52; p < 0.001) compared to controls, but decreased in axSpA (OR 0.82; 95% CI 0.70, 0.96; p = 0.012). CONCLUSION: RA and PsA, but not axSpA, are associated with an increased odds of MetS. Holistic management strategies that address both IA and MetS are essential for improving mortality and morbidity.

Humans↗

PubMed2026

Definition and prevalence of residual disease in inflammatory arthritis: a systematic literature review and meta-analysis.

OBJECTIVE: To assess how residual disease (i.e., clinically relevant signs/symptoms despite achieving treatment targets) is defined in rheumatoid arthritis (RA), psoriatic arthritis (PsA) or axial spondyloarthritis (axSpA), and estimate the prevalence/severity of residual disease in these diseases. METHODS: Systematic review of original research in RA/PsA/axSpA. Two key residual disease components were extracted: (1) the patient's disease state (often remission/low disease activity) and (2) which residual signs/symptoms were measured, e.g. swollen joints or fatigue (indicators of residual disease). Frequencies of the disease states and indicators were described (Objective 1). Prevalence (%) and severity (absolute score on instrument, e.g. fatigue NRS) of residual disease was analysed by indicator, using random effects meta-analysis (≥4 studies) or descriptively (<4 studies) (Objective 2). RESULTS: Regarding residual disease definitions (59 studies), disease states were almost exclusively disease activity-based (>99%), but with much variation in specific instruments/thresholds. Across diseases, physician-reported (66%) and patient-reported (73%) indicators were used more often than laboratory indicators to define residual disease (46%). Especially peripheral joint counts, pain, physical function and CRP were frequently used (42-56% of studies). The prevalence of residual disease (84 studies) was notable. For example, 5-25% of RA and PsA patients in remission still had swollen joints, and up to one-third reported relevant pain or fatigue. For axSpA, evidence was limited. CONCLUSION: Residual disease definitions in RA/PsA/axSpA are based on various disease activity instruments/thresholds and indicators (signs/symptoms). Residual disease affects up to half of patients. Future research should aim for a consensus-based definition of residual disease.

Humans↗