Patients with Common Variable Immunodeficiency Complicated by Autoimmune Phenomena Have Lymphopenia and Reduced Treg, Th17, and NK Cells

Abstract

Most patients with primary immune deficiency suffer from recurrent infections; however, paradoxical autoimmune phenomena can also manifest. The aim of this study was to identify immunological markers of autoimmune phenomena associated with common variable immunodeficiency (CVID). The study included 33 adults with CVID divided into two groups: (1) those with noninfectious autoimmune complications (CVID-C (n = 24)) and (2) those with only infectious symptoms (CVID-OI (n = 9)). Flow cytometry of peripheral blood was performed and compared with systemic lupus erythematosus (SLE) patients (n = 17) and healthy controls (n = 20). We found that all lymphocytes were lower in CVID-C and SLE. NK cells were lowest in CVID-C. Th17 cells were significantly reduced in CVID-C and SLE. Tregs were significantly lower in CVID-C and SLE. Bregs did not significantly differ between any groups. Class-switched memory B cells were significantly lower in CVID-C and CVID-OI. Lastly, plasmablasts were significantly higher in SLE. Among the T cell subsets, CVID-C patients had lower naive and recent thymic emigrant CD4+ T cells. In conclusion, reduced Treg, Th17, and NK cells are features of CVID with autoimmune complications, and class-switched memory B cells can help distinguish patients with different causes of autoimmunity. Future studies are needed to confirm whether reductions of Treg, Th17, and NK cells might be a biomarker of more complicated CVID cases.

Elevated CD21low B Cell Frequency Is a Marker of Poor Immunity to Pfizer-BioNTech BNT162b2 mRNA Vaccine Against SARS-CoV-2 in Patients with Common Variable Immunodeficiency

“…Interestingly, patients with a poor vaccine response had lower levels of central memory (CM) cells, particularly CM Th2 and Th17 cells (Figure 3F ). These findings suggest that the subgroup of CVID-patients with reduced levels of specific T-cell subsets, previously connected to autoimmune complications, also may suffer from a poor vaccine response to mRNA vaccination [ 21 , 23 ].…”

Case report: Cellular therapy for hydroa vacciniforme-like lymphoproliferative disorder in pediatric common variable immunodeficiency with chronic active Epstein-Barr virus infection

“…Infections in CVID are most often of bacterial etiology. Serious viral infections, including CMV and EBV, are less characteristic (8,24). It cannot be ruled out that in the presented patient the cause of the severe course of EBV and CMV infection in infancy may be a genetic predisposition resulting from the coexistence of STX11 and TACI mutations.…”

Immune Dysregulation in Pediatric Common Variable Immunodeficiency: Implications for the Diagnostic Approach

“…Although numerous heterogeneous disturbances of immune homeostasis within the peripheral lymphocyte pools have been observed in CVID ( 20 , 37 – 39 ), yet similar lymphocyte subset abnormalities in pediatric CVID have also been reported ( 18 ). Furthermore, a flow cytometric analysis of peripheral B and T lymph cells in children manifesting lymphoproliferative disorders has revealed developmental abnormalities of total CD19+ and switched memory B cells along with T cells subsets, such as RTE, naive Th, and Treg cells.…”

“…The pathomechanisms of immune dysregulation with autoimmune, lymphoproliferative, and autoinflammatory phenotypes in pediatric CVID have not been hitherto clearly defined. Several components of the lymphocyte compartment, such as but not limited to increased immature CD21low B cell and decreased switched memory B-cell subsets along with depleted naive T CD4+ helper and T regulatory, as well as T CD8+ cytotoxic T cells, have been proposed as biomarkers ( 18 , 20 ).…”