Circulating angiogenic T cells as potential immune-vascular biomarkers associated with disease activity in axial spondyloarthritis

Objective Axial spondyloarthritis (axSpA) is a chronic inflammatory autoimmune disease associated with persistent systemic inflammation and endothelial dysfunction. Angiogenic T cells (Tang cells), defined as CD3 + CD31 + CD184 + T cells, are specialized immune cells involved in vascular repair and endothelial homeostasis, but their clinical relevance in axSpA remains unclear. This study aimed to characterize circulating Tang cells in axSpA and evaluate their potential as immune-vascular biomarkers of disease activity. Methods Peripheral blood samples were obtained from patients with axSpA stratified by disease activity and from healthy controls. Circulating Tang cells and their phenotypic subsets were quantified using flow cytometry. Clinical characteristics, disease activity indices (ASDAS and BASDAI), inflammatory markers, and immunometabolic parameters were collected. Correlation analyses, multivariable logistic regression, and receiver operating characteristic (ROC) curve analyses were performed to assess the clinical significance of Tang cells in relation to axSpA disease activity. Results Tang cell frequency and absolute count were significantly decreased in active axSpA (median 16.40% [11.97%-25.65%]; 195.82 [135.07-322.53] cells/µL) compared with stable axSpA (32.11% [24.62%-42.33%]; 442.89 [306.48-633.02]) and healthy controls (32.23% [26.57%-43.87%]; 437.95 [293.73-507.95]) (all P < 0.001). Tang cell frequency showed a positive correlation with CD14 + HLA-DR + monocyte proportions (Spearman r = 0.537, P < 0.001) and an inverse correlation with BASDAI scores (Spearman r = −0.548, P < 0.001). Multivariable regression analysis revealed that circulating Tang cell frequency remained independently and inversely associated with active disease status (OR = 0.87, 95% CI: 0.79 - 0.95, P = 0.002) after adjustment for traditional inflammatory markers including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). In addition, circulating Tang cells showed satisfactory discriminatory ability to distinguish active axSpA from stable axSpA (area under the curve [AUC] = 0.831). Conclusions Circulating angiogenic T cells are inversely associated with disease activity in axSpA and represent a novel immune-vascular biomarker that is not redundant with traditional inflammatory parameters. These findings provide a clinical immunophenotypic framework highlighting altered vascular repair-immune interactions in axSpA and support further functional studies to clarify the functional role of Tang cells in disease pathogenesis.