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.
Highlights
Hypogammaglobulinemia as a consequence of hematological malignancies, systemic disorders causing excessive loss or catabolism of immunoglobulins, viral infections or drugs, such as antiepileptic agents and anti-inflammatory medications, is defined as secondary hypogammaglobulinemia [1,2]
Secondary hypogammaglobulinemia appears to have a later onset than primary immunodeficiency disorders (PID), as its diagnosis was made at a later age than PID ((53.42 y Vs. 38.5 y (IQR: 24.75–53.75))
Consistent with previous studies, suggesting the safety of most biologics with respect to the risk of infections [35,36,37], all studied rheumatic patients were diagnosed with hypogammaglobulinemia while treated with anti-inflammatory regimens containing conventional disease-modifying anti-rheumatic drugs (DMARD)
Summary
Hypogammaglobulinemia as a consequence of hematological malignancies, systemic disorders causing excessive loss or catabolism of immunoglobulins, viral infections or drugs, such as antiepileptic agents and anti-inflammatory medications, is defined as secondary hypogammaglobulinemia [1,2]. Its exclusion is required for the diagnosis of primary immunodeficiency disorders (PID) [3]. Besides bacterial infections due to primary antibody failure, CVID may manifest with autoimmunity, granulomatous and/or lymphoproliferative disease [6]. Autoimmunity in CVID includes rheumatic disease, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and Sjögren’s syndrome (SS) [7,8,9]. These conditions necessitate anti-inflammatory treatment, which could lead to hypogammaglobulinemia even in the absence of a PID
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