# CXCL13 as a Biomarker of Complex Common Variable Immunodeficiency

## TL;DR

This study shows that CXCL13 levels in blood can help identify and categorize patients with Common Variable Immunodeficiency based on their immune and clinical features.

## Contribution

The study introduces CXCL13 as a novel biomarker for classifying complex CVID subtypes and predicting clinical severity.

## Key findings

- CVID patients had higher serum CXCL13 levels compared to healthy donors, particularly in females.
- CXCL13 levels correlated with clinical complications and immune markers like CD21low B cells and cTfh counts.
- Higher CXCL13 levels were associated with more severe disease features in CVID patients.

## Abstract

Common Variable Immunodeficiency (CVID) is a group of heterogeneous disorders with common denominators of impaired antibody production and function, and recurrent infections. Currently, prognostic biomarkers for CVID are limited. CXCL13 is a critical regulator of germinal centre responses and antibody production, with T follicular helper (Tfh) cells as a major source, and acts as a potent B cell chemoattractant. Serum levels of CXCL13 are increased in chronic inflammatory conditions and malignancy.

We aimed to explore whether serum CXCL13 levels are altered in CVID and whether they can categorise the patients based on their clinical and immune phenotype.

We compared the serum levels of CXCL13 between CVID and healthy donors (HD) and associated them with the clinical and immune phenotype of the patients.

The serum levels of CXCL13 were higher in CVID, especially in female patients, as compared to HD, and were positively correlated with the number of clinical complications in CVID and the total peripheral circulating Tfh cells (cTfh). CVID patients with higher levels of CXCL13 were more likely to have clinical complications and/or high frequency of CD21low B cells or low frequency of switched memory B cells.

CXCL13 can categorise heterogeneous patients with CVID and be used as a biomarker of complex disease.

The online version contains supplementary material available at 10.1007/s10875-025-01963-2.