CXCL13 quantification in PBMCs and plasma distinguishes Sézary syndrome from other cutaneous T-cell lymphomas and dermatoses

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Frontiers in Medicine Published April 13, 2026 Medically reviewed May 1, 2026 DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Consider plasma CXCL13 quantification as a potential screening tool for suspected Sézary syndrome, noting limited utility of skin biopsy staining.

This cohort study evaluated CXCL13 expression in PBMCs and plasma CXCL13 concentrations in a population comprising patients with suspected SS, MF, AD, PS, EC, and healthy donors. The analysis included 51 samples for mRNA assessment and 142 patients for plasma analysis. CXCL13 immunohistochemical expression in skin biopsies served as a secondary outcome measure.

The primary results demonstrated significant upregulation of CXCL13 mRNA in PBMCs in SS patients compared with MF, AD, and healthy donors. Plasma CXCL13 concentrations were significantly higher in SS patients than in all other conditions and healthy donors. ROC analysis confirmed excellent performance of plasma CXCL13 as a differential marker, yielding an AUC of 93%. Immunohistochemical expression of CXCL13 in skin biopsies was broadly detected across all conditions.

No adverse events, serious adverse events, discontinuations, or specific tolerability data were reported in the study. A key limitation identified was that CXCL13 immunohistochemical expression in skin biopsies was broadly detected across all conditions, which limits its diagnostic value. The study did not report specific p-values or confidence intervals for the main comparisons, nor did it detail the absolute numbers for the effect sizes beyond the AUC.

Quantification of CXCL13 expression in PBMCs and measurement of plasma levels may represent practical screening tools to identify patients with suspected SS, facilitating earlier referral to specialized centres and prompt initiation of appropriate therapy. Clinicians should interpret these results cautiously given the lack of specificity in tissue staining and the need for further validation in larger, prospective cohorts.

Study Details

Study typeCohort

EvidenceLevel 3

PublishedApr 2026

View Original Abstract ↓

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.