In-depth immune profiling reveals advanced B- and T-cell differentiation to be associated with Th1-driven immune dysregulation in common variable immunodeficiency.

Abstract

Common variable immunodeficiency (CVID) is an inborn error of immunity characterized by low levels of antibodies. In addition to infections, many patients also suffer from T-helper 1-driven immune dysregulation, which is associated with increased mortality. The aim of this study was to perform in-depth characterization of the T and the B cell compartments in a well-defined cohort of patients affected by CVID and correlate the findings to the level of clinical immune dysregulation. We used mass cytometry, targeted proteomics, flow cytometry and functional assays to delineate the immunological phenotype of 15 CVID-affected patients with different levels of immune dysregulation. Unbiased clustering of T cell mass cytometry data correlated with CVID-related immune dysregulation and plasma protein profiles. Expanded CXCR3+ T-bet-expressing B cells correlated with effector memory CD4+ T cell clusters, and increased plasma levels of CXCR3-ligands. Our findings indicate an interplay between B cells and T cells in CVID-related immune dysregulation and provide a better understanding of the underlying pathological mechanisms.

• Authors: Jonas Hultberg, Emelie Blixt, Robin Göransson, Jörgen Adolfsson, Melissa Govender, Marie Larsson, Åsa Nilsdotter-Augustinsson, Jan Ernerudh, Sofia Nyström
• Journal: Clinical immunology (Orlando, Fla.) (Clin Immunol) Vol. 257 Pg. 109816 (Oct 31 2023) ISSN: 1521-7035 [Electronic] United States
• PMID: 37918468 (Publication Type: Journal Article)
• Copyright: Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.