Skewed Invariant Natural Killer T (iNKT) Cells, Impaired iNKT:B Cell Help and Decreased SAP Expression in Blood Lymphocytes from Patients with Common Variable Immunodeficiency

Abstract

Common variable immunodeficiency (CVID) is a syndrome with predominantly defective B cell function. However, abnormalities in the number and function of other lymphocyte subpopulations in peripheral blood (PB) have been described in most patients. We have analysed the distribution of iNKT cell subpopulations in the PB of CVID patients and the ability of these cells to provide in vitro cognate B cell help. The total of iNKT cells was reduced in the PB of CVID patients, especially CD4+, CD4-/CD8- and CCR5+/CXCR3+. These findings were associated with an enrichment of memory-like and a tendency towards a reduction in TNF-α-expressing effector iNKT cells in the peripheral blood mononuclear cells (PBMC) of CVID patients. Moreover, an accumulation of follicular helper iNKT cells in the PB of CVID patients was demonstrated. CVID αGalCer-pulsed iNKT cells are not able to induce autologous B cell proliferation although they do induce proliferation to healthy donor B cells. Interestingly, autologous and heterologous co-cultures did not differ in the amount of immunoglobulin secreted by B cells in vitro. Finally, reduced intracellular SAP expression in iNKT cells and other lymphocytes in the blood from CVID patients was observed. These results provide further insights into the immunological mechanisms underlying the iNKT cell defects and the potential targets to improve B cell help in CVID.

Common Variable Immunodeficiency: Epidemiology, Pathogenesis, Clinical Manifestations, Diagnosis, Classification, and Management

“…However, they also found that there was no difference in the frequency of circulating NKT cells between the patients and healthy controls. In contrast, a study on iNKT cells identified a marked decrease in the proportion of these cells that was associated with low or absent switched memory B cells, thus supporting a potential correlation between iNKT-cell and B-cell function [86].…”

“…Nevertheless, attributing causality to microbial changes due to the presence of low IgA level and impaired epithelial gut barrier remains challenging, and further research in this field is clearly needed. iNKT iNKT cells Decreased [86] Abbreviations: iNKT, invariant natural killer T cell; NKT, natural killer T cell.…”

Activation and Regulation of B Cell Responses by Invariant Natural Killer T Cells

“…Patients with CVID display defects in B cell differentiation, resulting in accumulations of naïve and less-differentiated B cell populations and depletions of class switched memory B cells and plasmablasts ( 135 , 136 ). This led Erazo-Borrás and co-workers ( 137 ) to investigate if the iNKT deficiency underlies the defect in B cell differentiation. They found that, although total iNKT cells were depleted, iNKT FH cells were expanded in the patients.…”

Application of the diagnostic criteria for Common Variable Immunodeficiency in resource-limited settings

“…There were no reports of immunophenotyping of B cell subpopulations in the clinical records. However, 22/42 patients had previous PB B cell analysis financially supported with funds from another report 20 and we performed 16 in the present study (Table 4). Regarding the analysis of the naïve T cells, six of these reports were found in the clinical records and 22 were performed in the course of the present study.…”

“…Missing subpopulation tests were financially supported with the budget of the present and previous research grants in the reachable patients because they required these evaluations in the workflow. 20 Clinical information and serum Ig levels were found in all the clinical records included. There were no reports of immunophenotyping of B cell subpopulations in the clinical records.…”