Abstract
BACKGROUND: Anifrolumab (ANI), a monoclonal antibody blocking the type I interferon (IFN) receptor, is approved for systemic lupus erythematosus (SLE); yet real-world responses vary. We aimed to identify biomarkers predicting clinical response to ANI in SLE. METHODS: We prospectively enrolled patients with SLE who initiated ANI and evaluated immune cell subsets and type I IFN-associated markers by flow cytometry with respect to clinical response to ANI. Clinical response at 6 months was classified into responders and non-responders based on two criteria: achievement of a British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response and successful glucocorticoid tapering. RESULTS: Of the 31 patients analyzed, 15 were responders and 16 were non-responders. Among the ten biomarkers that showed significant changes in responders, four - CD317 expression on T cells, CD317 expression on B cells, CD169 expression on monocytes, and T-peripheral-helper-cell frequency - were already higher at baseline in responders than in non-responders. Baseline CD317 expression on T cells showed the highest discriminative power in predicting 6-month response, separating responders from non-responders with an AUC of 0.89, surpassing the four-gene IFN gene signature (IFNGS) measured by quantitative PCR (qPCR) (DeLong's test, P = 0.044). CONCLUSIONS: This study demonstrates that higher baseline CD317 expression on T cells is associated with a favorable clinical response to ANI and predicts this response more accurately than the previously proposed IFNGS in patients with SLE. These findings identify CD317 as a promising and practical candidate biomarker to guide personalized treatment strategies in SLE, contingent upon further validation.