Abstract
OBJECTIVE: A dysregulated immune response is involved in the pathogenesis of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). These diseases have been reported as immune-related adverse events in patients with cancer treated with immune checkpoints inhibitors. In this cross-sectional study, the relationship between soluble immune checkpoint molecules (sICMs) and clinical/imaging features of PMR and GCA was investigated. METHODS: Consecutive patients with PMR diagnosed according to the criteria by Bird et al were compared with age- and sex-matched healthy controls. Patients with PMR and overlapping GCA had to also satisfy the 1990 ACR classification criteria for GCA. All patients underwent standardized clinical, laboratory examination, and (18)F-fluorodeoxyglucose positron emission tomography/computed tomography scans. The sICM anticytotoxic T Ly-4, the programmed cell death protein 1 (PD-1), and PD-1 ligands PD-L1 and PD-L2 were measured by enzyme-linked immunosorbent assay. RESULTS: Forty patients (80% women, mean age 76 years, and mean disease duration 88 days) were assessed. Of these, 30 had isolated PMR and 10 had PMR with GCA. Patients showed significantly higher concentrations of all sICMs compared with controls (P < 0.001). Conditional logistic regression revealed the strong discriminative capacity of these molecules between patients and healthy controls, with PD-1 showing complete separation among groups (effect size = 0.78) and PD-L1 (odds ratio [OR] 134.33, P < 0.001) and PD-L2 (OR 63.00, P < 0.001) demonstrating the strongest ability to distinguish patients from controls. Correlations between sICM levels and clinical features were generally weak or absent, with no significant differences based on disease phenotype or glucocorticoid exposure. Results were similar in glucocorticoid-naive patients. CONCLUSION: sICMs are significantly elevated in PMR and GCA and strongly differentiate patients from healthy controls. Although they do not correlate with clinical or imaging features, their consistent elevation in active disease might suggest a complex interplay between innate and adaptive immunity.