Abstract
Common variable immunodeficiency is the most common clinical primary immunodeficiency in adults. Its hallmarks are hypogammaglobulinemia and compromised B-cell differentiation into memory or antibody-secreting cells leading to recurrent infections. This disease is heterogeneous, with some patients harboring multiple complications such as lymphoproliferative disorders, autoimmune manifestations, or granulomatous inflammation. The mechanisms leading to these complications remain elusive despite numerous associations found in the literature. For instance, although described as a B cell intrinsic disease, numerous abnormalities have been reported in other immune cell compartments. Here, we tuned our attention to follicular helper T cells, a CD4+ T cell population specialized in B cell help, considering the recent publications showing an involvement of these cells in CVID pathogenesis.
Highlights
Common variable immunodeficiency (CVID) is an umbrella name for the most common symptomatic, and the most heterogeneous, primary antibody deficiency in adults
Mutations in several genes encoding for B cell receptor complex associated proteins, B cell activating factor receptor (BAFF-R), inducible co-stimulator (ICOS), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), phosphatidylinositol 3-kinase (PI3K), and in lipopolysaccharide-responsive beige-like anchor (LRBA) protein or more recently the NFκB family have been described [5,6,7]
A recent study from Le Coz et al highlighted that part of the naïve CD4 T cells from CVID patients with autoimmune cytopenias (AIC) are skewed toward a follicular commitment based on their expression of specific markers (CXCR5, programmed cell death 1 (PD-1), CCR7, CD38, ICOS, Tcell factor 1)
Summary
Common variable immunodeficiency (CVID) is an umbrella name for the most common symptomatic, and the most heterogeneous, primary antibody deficiency in adults. Following influenza vaccination, TFH1 (known as non-helpers) can be activated to express ICOS and high levels of PD-1, correlating with antibody responses This means that they are able to help memory B cells in vitro, showing a limited B helper cell function [46]. Our group [75] and others [76,77,78] observed an increase of circulating TFH (memory CXCR5+ CD4 T cells) in CVID patients harboring non-infectious complications. A recent study from Le Coz et al highlighted that part of the naïve CD4 T cells from CVID patients with autoimmune cytopenias (AIC) are skewed toward a follicular commitment based on their expression of specific markers (CXCR5, PD-1, CCR7, CD38, ICOS, Tcell factor 1). Despite recent studies, the mechanisms leading to the imbalance of TFH1 vs. TFH2/TFH17 in CVID patients still need to be fully decoded
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
