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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Clin+Immunol
2016 ; 36
(7
): 656-66
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Phenotypic and Functional Comparison of Class Switch Recombination Deficiencies
with a Subgroup of Common Variable Immunodeficiencies
#MMPMID27484504
Aan de Kerk DJ
; Jansen MH
; Jolles S
; Warnatz K
; Seneviratne SL
; Ten Berge IJ
; van Leeuwen EM
; Kuijpers TW
J Clin Immunol
2016[Oct]; 36
(7
): 656-66
PMID27484504
show ga
Primary antibody deficiencies (PADs) are the most common immunodeficiency in
humans, characterized by low levels of immunoglobulins and inadequate antibody
responses upon immunization. These PADs may result from an early block in B cell
development with a complete absence of peripheral B cells and lack of
immunoglobulins. In the presence of circulating B cells, some PADs are
genetically caused by a class switch recombination (CSR) defect, but in the most
common PAD, common variable immunodeficiency (CVID), very few gene defects have
as yet been characterized despite various phenotypic classifications. Using a
functional read-out, we previously identified a functional subgroup of CVID
patients with plasmablasts (PBs) producing IgM only. We have now further
characterized such CVID patients by a direct functional comparison with patients
having genetically well-characterized CSR defects in CD40L, activation-induced
cytidine deaminase (AID) and uracil N-glycosylase activity (UNG). The CSR-like
CVID patients showed a failure in B cell activation patterns similar to the
classical AID/UNG defects in three out of five CVID patients and distinct more
individual defects in the two other CVID cases when tested for cellular
activation and PB differentiation. Thus, functional categorization of B cell
activation and differentiation pathways extends the expected variation in CVID to
CSR-like defects of as yet unknown genetic etiology.