Age-related changes in serum immunoglobulins in patients with familial IgA deficiency and common variable immunodeficiency (CVID)

Johnson, Micah A.; Keeton, L. G.; Zhu, Zeng-Bian; Volanakis, John E.; Cooper, Max D.; Schroeder, Harry W.

doi:10.1046/j.1365-2249.1997.3801278.x

Cited by 47 publications

(30 citation statements)

References 35 publications

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“…Spontaneous resolution of immunodeficiency has been noted previously, suggesting that this immunodeficiency is not always an intrinsically permanent B-cell defect, or that this more transient form cannot currently be distinguished from CVID (17,31).…”

Section: Discussionmentioning

confidence: 90%

Clinical and Immunological Features of 65 Iranian Patients with Common Variable Immunodeficiency

Aghamohammadi

Farhoudi

Moin

et al. 2005

Clin Vaccine Immunol

112

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Common variable immunodeficiency (CVID) is a primary immunodeficiency disease characterized by hypogammaglobulinemia and recurrent bacterial infections. The records of 65 patients with CVID (37 males and 28 females) in the age range of 24 to 537 months were reviewed. By the year 2003, 11 patients had died and seven patients could not be located. The total follow-up period was 221 patient-years. The median diagnostic delay (time between onset and diagnosis) in our patient group was 60 months. At the time of diagnosis, the baseline serum immunoglobulin G (IgG), IgM, and IgA levels were below the level normal for the patients' age; the medians for this group were 120, 10, and 0 mg/dl, respectively. All of the patients presented with infectious diseases at the time of onset, the most common of which were otitis media, diarrhea, pneumonia, and sinusitis. Acute and recurrent infections were also found in almost all of the patients, particularly involving respiratory and gastrointestinal systems. The most common infections, before diagnosis and during follow-up, were pneumonia, acute diarrhea, acute sinusitis, and otitis media. CVID should be considered in any patient with a history of recurrent infections and decreased levels of all serum immunoglobulin isotypes.

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Section: Discussionmentioning

confidence: 90%

Clinical and Immunological Features of 65 Iranian Patients with Common Variable Immunodeficiency

Aghamohammadi

Farhoudi

Moin

et al. 2005

Clin Vaccine Immunol

112

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“…In patients with SIgAD, the level of memory B cells was similar to control group, whereas the subset of classswitched memory B cells within a population of memory B cells displayed abnormalities similar to those seen in children with CVID. Some similarities between behavior of B-cell compartment in CVID and symptomatic SIgAD may provide additional evidence for the linkage of these entities (19,21,23). Patients with SIgAD in whom the level of class-switched memory B cells has been profoundly decreased, require further observation as to whether they may develop CVID.…”

Section: Discussionmentioning

confidence: 95%

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

et al. 2009

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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...

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“…Clinical features of IgAD/CVID also resemble those found in other autoimmune disorders, including 1) the occurrence of antiIgA Ab that are present at a higher frequency in patients with autoimmune complications than in asymptomatic IgAD (65); 2) the increased prevalence of autoimmune disease in IgAD/CVID (65); 3) frequent disease manifestation after an episode of other autoimmune phenomena; 4) variable disease severity; and 5) a slow, gradual appearance of hypogammaglobulinemia over many years (12). A transmission of IgAD to a healthy sibling by bone marrow transplantation (66) may have been due to the transfer of autoreactive T cell clones.…”

Section: Discussionmentioning

confidence: 95%

Fine-Scale Mapping at IGAD1 and Genome-Wide Genetic Linkage Analysis Implicate HLA-DQ/DR as a Major Susceptibility Locus in Selective IgA Deficiency and Common Variable Immunodeficiency

Královičová

Hammarström

Plebani

et al. 2003

The Journal of Immunology

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Selective IgA deficiency (IgAD) and common variable immunodeficiency (CVID) are the most common primary immunodeficiencies in humans. A high degree of familial clustering, marked differences in the population prevalence among ethnic groups, association of IgAD and CVID in families, and a predominant inheritance pattern in multiple-case pedigrees have suggested a strong, shared genetic predisposition. Previous genetic linkage, case-control, and family-based association studies mapped an IgAD/CVID susceptibility locus, designated IGAD1, to the MHC, but its precise location within the MHC has been controversial. We have analyzed a sample of 101 multiple- and 110 single-case families using 36 markers at the IGAD1 candidate region and mapped homozygous stretches across the MHC shared by affected family members. Haplotype analysis, linkage disequilibrium, and homozygosity mapping indicated that HLA-DQ/DR is the major IGAD1 locus, strongly suggesting the autoimmune pathogenesis of IgAD/CVID. This is supported by the highest excess of allelic sharing at 6p in the genome-wide linkage analysis of 101 IgAD/CVID families using 383 marker loci, by previously reported restrictions of the T cell repertoires in CVID, the presence of autoantibodies, impaired T cell activation, and a dysregulation of a number of genes in the targeted immune system. IgAD/CVID may thus provide a useful model for the study of pathogenesis and novel therapeutic strategies in autoimmune diseases.

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Age-related changes in serum immunoglobulins in patients with familial IgA deficiency and common variable immunodeficiency (CVID)

Cited by 47 publications

References 35 publications

Clinical and Immunological Features of 65 Iranian Patients with Common Variable Immunodeficiency

Clinical and Immunological Features of 65 Iranian Patients with Common Variable Immunodeficiency

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

Fine-Scale Mapping at IGAD1 and Genome-Wide Genetic Linkage Analysis Implicate HLA-DQ/DR as a Major Susceptibility Locus in Selective IgA Deficiency and Common Variable Immunodeficiency

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