The mechanisms underlying cytotoxic immune dysfunction in ankylosing spondylitis (AS) remain incompletely understood. While systemic inflammation is a hallmark of AS, traditional inflammatory markers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) may not adequately reflect immune functional status. This study aimed to investigate differences in cytotoxic lymphocyte function between AS patients and healthy controls, and to evaluate the roles of body mass index (BMI), inflammatory markers, and nutritional-inflammatory indices in modulating immune function.

This retrospective study included 216 patients with ankylosing spondylitis and 229 healthy controls. Cytotoxic immune function was assessed by measuring perforin and granzyme expression in T cells, natural killer T (NKT) cells, and cytotoxic T lymphocytes (CD8+ T cells). A comprehensive analytical strategy was applied, including group comparisons, multiple BMI stratifications, inflammatory marker analyses, subgroup combination analyses, correlation analyses, and multivariable regression models. Stratified analyses based on platelet-to-albumin ratio (PAR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) were performed to validate the findings.

Compared with healthy controls, patients with AS exhibited significantly reduced cytotoxic lymphocyte function, as reflected by lower perforin and granzyme expression and decreased co-expression levels, despite relatively preserved immune cell proportions. BMI showed no consistent association with immune parameters across multiple classification strategies. Similarly, CRP and ESR were not significantly associated with cytotoxic immune function. In contrast, PAR demonstrated a robust and consistent positive association with perforin and granzyme expression across multiple immune cell subsets, particularly in CD8+ T cells. Conversely, SII and platelet-related indices were significantly negatively associated with cytotoxic function. Notably, NLR showed a positive association with certain functional markers, suggesting a potential role in immune activation. These findings were consistently supported by stratified analyses.

AS is characterized by impaired cytotoxic lymphocyte function that is not explained by BMI or traditional inflammatory markers. Instead, immune function appears to be primarily regulated by the balance between nutritional status and inflammatory burden. PAR acts as a key positive regulator, whereas platelet-related inflammatory indices exert suppressive effects. These findings highlight a functional rather than quantitative immune dysregulation in AS and provide novel insights into immune modulation in inflammatory diseases.