Peripheral Blood Lymphocyte Phenotype Differentiates Secondary Antibody Deficiency in Rheumatic Disease from Primary Antibody Deficiency

Abstract

The phenotype of primary immunodeficiency disorders (PID), and especially common variable immunodeficiency (CVID), may be dominated by symptoms of autoimmune disorders. Furthermore, autoimmunity may be the first manifestation of PID, frequently preceding infections and the diagnosis of hypogammaglobulinemia, which occurs later on. In this case, distinguishing PID from hypogammaglobulinemia secondary to anti-inflammatory treatment of autoimmunity may become challenging. The aim of this study was to evaluate the diagnostic accuracy of peripheral blood lymphocyte phenotyping in resolving the diagnostic dilemma between primary and secondary hypogammaglobulinemia. Comparison of B and T cell subsets from patients with PID and patients with rheumatic disease, who developed hypogammaglobulinemia as a consequence of anti-inflammatory regimes, revealed significant differences in proportion of naïve B cells, class-switched memory B cells and CD21low B cells among B cells as well as in CD4+ memory T cells and CD4+ T follicular cells among CD4+ T cells. Identified differences in B cell and T cell subsets, and especially in the proportion of class-switched memory B cells and CD4+ T follicular cells, display a considerable diagnostic efficacy in distinguishing PID from secondary hypogammaglobulinemia due to anti-inflammatory regimens for rheumatic disease.

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

“…Patients with CVID and SLE both had lymphopenia. We found that only a more detailed analysis of peripheral lymphocyte subset counts showed differences; specifically, smB cells and plasmablasts were reduced in CVID, which is in agreement with other studies [ 30 ]. Therefore, low smB cells detected in patients with autoimmunity should increase the awareness of immunodeficiency.…”

“…Until now, studies comparing B and T cell subsets from patients with PID and patients with rheumatic diseases are limited. In one study, patients with primary and secondary hypogammaglobulinemia in the course of different rheumatic diseases were observed [ 30 ]. Another study involved the analysis of polymyalgia rheumatica patients treated with systemic glucocorticoids [ 31 ].…”

Primary antibody deficiency-associated arthritis shares features with spondyloarthritis and enteropathic arthritis

“…Evaluation of tolerability would be especially relevant in view of the immunosuppressive effect of diverse csDMARDs and dDMARDs, which may worsen the PAD-intrinsic immunodeficiency. 54 41 In the present study, only a minority of patients developed infectious complication as a consequence of their arthritis treatment, which may underestimate the impact of DMARDs and their immunosuppressive effect on patients’ immunodeficiency. The latter may depend on several parameters, including concomitant glucocorticoid treatment, the type of PAD as well as the vaccination status of tested patients, which should be evaluated through perspective studies with large numbers of treated patients.…”

Common Variable Immunodeficiency-Associated Cancers: The Role of Clinical Phenotypes, Immunological and Genetic Factors

“…Whole blood was collected in ethylene diamine tetraacetic acid (EDTA) tubes, and peripheral blood mononuclear cell (PBMC) preparations have been performed as described previously ( 23 ). PBMCs were cryopreserved in freezing medium (heat-inactivated fetal calf serum (FCS), PAN-Biotech; 10% v/v dimethyl sulfoxide, Sigma) until use.…”

“…To calculate standardized incidence ratios (SIRs), all patients were stratified by age and gender. Data on the reference population were derived from the 12th edition of the “Cancer in Germany” report by the Robert Koch Institute ( 23 ). The expected number of cases for each type of cancer in the studied patient cohort was calculated based on the age- and gender-specific incidence rate provided in the aforementioned report.…”