Defects in memory B-cell and plasma cell subsets expressing different immunoglobulin-subclasses in patients with CVID and immunoglobulin subclass deficiencies

Abstract

IgAdef, B-cell defects were mainly restricted to surface membrane (sm)IgA 1 PCs and MBCs, with 2 clear subgroups showing strongly decreased numbers of smIgA 1 PCs with mild versus severe smIgA 1 MBC defects and higher frequencies of nonrespiratory tract infections, autoimmunity, and affected family members. Patients with IgG subclass deficiency with IgA deficiency and those with CVID showed defects in both smIgA 1 and smIgG 1 MBCs and PCs. Reduced numbers of switched PCs were systematically found in patients with CVID (absent in 98%), with 6 different defective MBC (and clinical) profiles: (1) profound decrease in MBC numbers; (2) defective CD27 1 MBCs with almost normal IgG 3 1 MBCs; (3) absence of switched MBCs; and (4) presence of both unswitched and switched MBCs without and; (5) with IgG 2 1 MBCs; and (6) with IgA 1 1 MBCs. Conclusion: Distinct PAD defective B-cell patterns were identified that are associated with unique clinical profiles. (J

Reproducibility of Flow Cytometry Through Standardization: Opportunities and Challenges

“…B cells were further phenotyped by 8-color panels to describe PreGC and PostGC development and by 12-color panel revealing the IgH-isotype expressing cells (53,54). The same panel was used by the EuroFlow PID consortium to investigate primary antibody deficiency (55).…”

Defining B-cell defects and correlation with complications in patients with common variable immune deficiency

“…The importance of using age-matched control subjects is emphasized in the article because many diagnostic laboratories still use adult levels of B-cell subpopulations for comparisons with their patients. Overall decreased IgA 1 1 and/or IgA 2 1 plasma cell counts were found in all patients, except for 2 patients with SIgAD who showed abnormally reduced numbers of surface membrane IgA 1 1 and IgA 2 1 memory B cells, confirming the failure of IgA production, which is in line with severely reduced serum IgA levels. The authors defined 2 subgroups of patients with SIgAD: those with mild reductions in numbers of surface membrane IgA 1 memory B cells and those with severely reduced numbers of surface membrane IgA 1 memory B cells.…”

“…The interesting article in this issue entitled ''Defects in memory B-cell and plasma cell subsets expressing different immunoglobulin-subclasses in patients with CVID and immunoglobulin subclass deficiencies'' from the EuroFlow group led by Jacques van Dongen, 1 updates the EUROclass classification 2 and confirms and extends an earlier study from the group, which was previously in Rotterdam 3 and now in Leiden. Use of an extended panel of mAbs to define 41 circulating B-cell and plasma cell subsets adds to our knowledge of the differing B-cell abnormalities in patients with selective IgA deficiencies (SIgADs) and those with common variable immunodeficiency disorders (CVIDs).…”

Issue Highlights – May 2019

“…Enumeration of blood CD4+ T‐cell counts in subjects infected with human‐immunodeficiency virus (HIV) is the first and one of the most well‐established clinical applications of flow cytometry. In turn, enumeration of other lymphoid and myeloid cell populations has also proven to be of diagnostic utility in other immune diseases, particularly in the diagnostic work‐up and classification of primary immunodeficiencies . A critical step in defining altered immune cell profiles is the definition of reference values.…”