The B-cell Compartment in the Peripheral Blood of Children With Different Types of Primary Humoral Immunodeficiency

Abstract

ABSTRACT:The aim of this study was to evaluate the B-cell compartment in the peripheral blood of children with different types of hipogammaglobulinemia: common variable immunodeficiency (CVID), transient hypogammaglobulinemia of infancy (THI), and selective IgA deficiency (SIgAD). We analyzed by flow cytometry the changes in the B-cell subsets with age and showed that children with an early-onset CVID develop similar pattern of B-cell subsets as adult patients with CVID with age, as the levels of memory B cells (CD19 ϩ /CD27 ϩ ) and class-switched memory B cells (, in contrast to age-matched control group, did not increase with age. Children with SIgAD displayed similar changes as patients with CVID only within the class-switched memory B-cell subpopulation. No significant differences in the level of memory B cells and class-switched memory B cells in children with THI in comparison to age-matched control group were observed. There were no differences in the percentage of immature B cells (CD19 ϩ /CD21 low ) among all studied groups. As B-cell subsets in children with THI were normal during entire period of hypogammaglobulinemia, the persistence of low levels of memory B-cell subsets in some children may facilitate the diagnosis of CVID. (5), or primary B-cell defects (6,7) have been reported. In some patients with CVID, defects in B-cell receptors signaling and B cell development have been described, especially mutations in CD19 (8), B-cell activating factor of the tumor necrosis factor family receptor (BAFF-R) (9), inducible costimulator of activated T cells (ICOS) (10), and transmembrane activator and CAML interactor (TACI) (11-14), which are required for maturation of B cells and generation of antibody diversity. Disease is usually diagnosed in the second or third decade of life after a history of recurrent pyogenic sinopulmonary infections (15), but some cases of CVID are diagnosed in the childhood as an early-onset CVID.Selective IgA deficiency (SIgAD) is the most prevalent primary humoral immunodeficiency. The clinical picture of SIgAD may vary from absence of clinical manifestations to fully symptomatic form (16). A variety of pathologic mechanisms of SIgAD have been postulated, which include the occurrence of IgA-specific T suppressor cells, inadequate T helper (Th) cell function, an intrinsic B-cell defects (17), or decreased expression of CD40 on monocytes (18). In most cases, the molecular defect is unknown, although in some patients with SIgAD, mutations in TACI gene have been identified (11,12). SIgAD is considered to be genetically linked with CVID, as the latter may develop from SIgAD (19 -21) and occasionally vice versa (22). Familial studies have implicated the existence of an allelic relationship between SIgAD and CVID, indicating that these disorders have the same molecular defect (23).Transient hypogammaglobulinemia of infancy (THI) is defined by decreased level of IgG (below 2 SD for the agematched healthy children) and in some cases low level of IgA and intact cell-mediated immunity. Prod...

The Heterogeneous Pathogenesis of Selective Immunoglobulin A Deficiency

“…They indicated a decrease in the frequency of switched memory cells, transitional cells as well as plasmablasts, and an increase in the CD21 low B cell subset compared to healthy individuals [53, 11]. In this sense, Celiksoy et al [51] demonstrated high counts of naive B cells in patients with SIgAD similar to CVID patients.…”

Immunologic Basis for Revaccination of HIV-Infected Children Receiving HAART

“…However, several studies have demonstrated an association between levels of viremia in HIV-infected adults and B-cell death through increased expression of activation markers on B cells, such as bcl-2, LAIR-1, Fas and Fas-L [27,29,30,62–65]. Increased activation-induced B-cell death is consistent with lower levels of CD27 + B cells in HIV-infected adults compared with uninfected adults [30,65].…”

B lymphocyte subsets and outcomes in patients with an initial diagnosis of transient hypogammaglobulinemia of infancy

“…Memory B cells can be further subdivided into marginal zone (MZ) B cells (CD19 + CD27 + IgM + IgD + ) and CSMB cells (CD19 + CD27 + IgM − IgD − ). The recirculating splenic MZ B cells synthesize IgM to a limited number of polysaccharide antigens without the help of T cells, while CSMB cells synthesize IgG, IgM and IgA in response to a wide variety of antigens with the help of follicular T cells …”