Evaluation of Expression of LRBA and CTLA-4 Proteins in Common Variable Immunodeficiency Patients

Immunol Invest. 2022 Feb;51(2):381-394. doi: 10.1080/08820139.2020.1833029. Epub 2020 Nov 15.

Abstract

Common variable immunodeficiency (CVID) is a primary immunodeficiency disease with a heterogeneous genetic background. Lipopolysaccharide-responsive beige-like anchor (LRBA), as well as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), have important regulatory roles in the immune responses. Here, we have investigated the expression of LRBA and CTLA-4 proteins in CVID patients with at least one presentation of early-onset occurrence, autoimmunity, or enteropathy. In this study, 20 newly diagnosed CVID patients without infection only phenotype, and ten healthy individuals were enrolled. The expressions of LRBA and CTLA-4 proteins were assessed by western blotting and flow cytometry, respectively. The patients were divided into two groups of autoimmunity-positive (11 cases) and autoimmunity-negative (9 patients). LRBA and CTLA-4 expressions were significantly lower in autoimmune-positive patients than in healthy individuals (P = .03 and P = .03, respectively). Autoimmune-negative patients had lower expression of LRBA and CTLA-4 than the control group, although it was not significant. There was a positive correlation between the expressions of LRBA and CTLA-4 in both groups of patients (P < .05). Furthermore, the highest frequency of LRBA (85.7%) and CTLA-4 (71.4%) defects was detected in those with concomitant presence of autoimmunity, enteropathy, and early-onset occurrence. Concurrent presence of autoimmunity, enteropathy, and early-onset occurrence in CVID patients could be indicative of a lack of expression in LRBA and CTLA-4 proteins. This could be helpful in early diagnosis and initiation of appropriate treatment in these patients prior to genetic confirmation.

Keywords: Common variable immunodeficiency (CVID); autoimmunity; cytotoxic T lymphocyte-associated antigen-4 (CTLA-4); early-onset occurrence; enteropathy; lipopolysaccharide (LPS)-responsive beige-like anchor (LRBA).

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Autoimmunity
  • CTLA-4 Antigen / genetics
  • Common Variable Immunodeficiency* / diagnosis
  • Common Variable Immunodeficiency* / genetics
  • Humans
  • Phenotype

Substances

  • Adaptor Proteins, Signal Transducing
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • LRBA protein, human