High baseline CD317 expression on T cells predicts favorable anifrolumab response in systemic lupus erythematosus

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.