CXCL13 as a simple and promising blood biomarker for differentiating Sézary syndrome from mycosis fungoides and other confounding chronic inflammatory skin diseases

Sézary syndrome (SS) is a rare and aggressive type of cutaneous T-cell lymphoma (CTCL). Due to its rarity and marked biological heterogeneity, SS diagnosis is frequently delayed, as it requires the integration of multiple complex diagnostic tests interpreted by highly specialized biomedical figures. In this context, we investigated the expression of CXCL13-increasingly implicated in several inflammatory and neoplastic skin disorders-as a potential screening biomarker to discriminate SS from mycosis fungoides (MF), the most common CTCL subtype, and from clinically overlapping inflammatory skin diseases, i.e. atopic dermatitis (AD), psoriasis (PS) and eczema (EC). Real-time PCR analysis of CXCL13 mRNA expression in 51 samples showed a significant upregulation in peripheral blood mononuclear cells (PBMCs) from SS patients compared with MF, AD and healthy donors (HD). Protein-level analysis in a larger cohort (n = 142), including allergic and atopic EC patients, revealed significantly higher plasma CXCL13 concentrations in SS than in all other conditions and HD, as assessed by ELISA. Receiver operating characteristic (ROC) analysis confirmed the excellent performance of plasma CXCL13 as a differential marker (AUC = 93%). In contrast, CXCL13 immunohistochemical expression in skin biopsies was broadly detected across all conditions, limiting its diagnostic value. In conclusion, quantification of CXCL13 expression in PBMCs and, more robustly, measurement of its plasma levels by widely available techniques such as RT-qPCR and ELISA may represent practical screening tools to identify patients with suspected SS. These assays could facilitate earlier referral to specialized centres for confirmatory testing and prompt initiation of appropriate therapy.