Combined decrease of defined B and T cell subsets in a group of common variable immunodeficiency patients

Moratto, Daniele; Gulino, Anna Virginia; Fontana, Stefania; Mori, Luigi; Pirovano, Silvia; Soresina, Annarosa; Meini, Antonella; Imberti, Luisa; Notarangelo, Luigi D.; Plebani, Alessandro; Badolato, Raffaele

doi:10.1016/j.clim.2006.07.003

Cited by 52 publications

(50 citation statements)

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“…Interestingly, the distribution of B-lymphocyte subpopulations is reminiscent of the situation found in patients with common variable immunodeficiency (CVID) (23)(24)(25)…”

Section: Discussionmentioning

confidence: 98%

Down Syndrome B-Lymphocyte Subpopulations, Intrinsic Defect or Decreased T-Lymphocyte Help

et al. 2010

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Down syndrome (DS) is known for increased incidence of respiratory infections and autoimmune diseases, indicating impaired immunity. Until now, attention has been mainly focused on T lymphocytes. Therefore, we determined B-lymphocyte subpopulations in 95 children with DS compared with 33 age-matched control (AMC) children. DS serum immunoglobulin levels were compared with 962 non-DS children with recurrent infections. The results were combined with clinical data. Transitional and naive B lymphocytes are profoundly decreased in the children with DS. This could be caused by an intrinsic B-lymphocyte defect resulting in (partial) failure of B-lymphocyte generation, decreased antigen-induced proliferation and/or increased apoptosis, or by decreased proliferation due to deficient T-lymphocyte help, or a combination of these. The decreased CD27ϩ , CD21 high , and CD23 ϩ cells are reminiscent of common variable immunodeficiency and suggestive of disturbed peripheral B-lymphocyte maturation. Immunoglobulin levels in DS are abnormal-as has been described before-and different from non-DS children with recurrent infections. We conclude that the humoral immune system is abnormal in DS, but could not find a relation between B-lymphocyte subsets, immunoglobulins and clinical features of the children with DS in our cohort, nor could we answer the question whether DS lymphocytes are truly intrinsically deficient, or could all findings be explained by deficient Tlymphocyte help. (Pediatr Res 67: 563-569, 2010)

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“…Interestingly, the distribution of B-lymphocyte subpopulations is reminiscent of the situation found in patients with common variable immunodeficiency (CVID) (23)(24)(25)…”

Section: Discussionmentioning

confidence: 98%

Down Syndrome B-Lymphocyte Subpopulations, Intrinsic Defect or Decreased T-Lymphocyte Help

et al. 2010

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“…Moratto et al also showed that the expressions of CXCR5 and CCR7 were reduced in a subset of CVID patients. 37 In addition, presence of autoimmune clinical findings was negatively correlated with CCR7 + cells ( Table 6). All of these findings support each other and the probable role of CCR7 + cells in CVID.…”

Section: Discussionmentioning

confidence: 99%

CD4⁺CD25⁺Foxp3⁺ T regulatory cells, Th1 (CCR5, IL-2, IFN-γ) and Th2 (CCR4, IL-4, Il-13) type chemokine receptors and intracellular cytokines in children with common variable immunodeficiency

Kütükçüler

Azarsız

Aksu

et al. 2015

Int J Immunopathol Pharmacol

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Common variable immunodeficiency (CVID) is a heterogeneous group of primary antibody deficiencies characterized by decreased serum immunoglobulin G along with a decrease in serum IgA and/or IgM, defective specific antibody production, and recurrent bacterial infections. Abnormal lymphocyte trafficking, dysregulated cellular responses to chemokines, and uncontrolled T cell polarization may be involved in the pathogenesis and may help to understand the clinical complications. We evaluated T helper cell subsets (chemokine receptors CCR4, CCR5, and CCR7), expressions on T lymphocytes, intracellular cytokines -IL-2, IL-4, IL-13, IFN-g-on CD4 + T cells, and expression of CD4 + CD25 + Foxp3 + regulatory T cells of 20 CVID patients and 26 healthy controls. Autoimmune clinical findings and other complications were also determined. Percentages and absolute numbers of CD4 + CD25 + Foxp3 + cells did not show any significant difference between CVID cases and healthy controls nor between severe and moderate disease patients. The only significant difference regarding Th1 and Th2 type intracellular cytokines was the decreased absolute numbers of CD3 + CD4 + IL4 + cells in CVID cases. There were some findings about T helper cell type dominance in CVID patients such as positive correlation between hepatomegaly and high IL-2 and IFN-g in CD3 + CD4 + cells and very high expression of CCR5 (Th1) on CD3 + CD4 + cells in patients with granuloma. Th1 (CCR5) and Th2 (CCR4) type chemokine receptors did not show any dominance in CVID cases. However, frequencies of CCR7 expressing CD3 + T cells, CD3 + CD4 + T helper cells and CD3 + CD8 + T cytotoxic cells were significantly lower in severe CVID patients. In addition, presence of autoimmune clinical findings was negatively correlated with CCR7 + cells. As CCR7 is a key mediator balancing immunity and tolerance in the immune system, the abnormality of this mediator may contribute to the profound immune dysregulation seen in CVID. In addition, Th1 cells seem to be more involved in the disease pathogenesis than Th2 cells.

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“…Recently, Moratto et al 32 examined 25 patients according to the Freiburg classification and confirmed the association of expanded CD21 low B cells with splenomegaly and autoimmune disease. In addition, these patients suffered from a higher incidence of lower respiratory tract infections and chronic lung disease, 32 neither of which was analyzed by the European trial. The immune dysregulation in these patients was extended to a severe reduction of naive CD45RA ϩ CD4 T cells, also described by Vlkova et al 33 The other findings of reduced total B-cell counts or CD4 T-cell counts in patients with expanded CD21 low B cells cannot be confirmed by this study.…”

Section: Discussionmentioning

confidence: 99%

The EUROclass trial: defining subgroups in common variable immunodeficiency

Wehr

Kivioja

Schmitt

et al. 2008

Blood

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IntroductionCommon variable immunodeficiency (CVID) is the most common primary immunodeficiency in adults. 1 Recurrent bacterial infections of the respiratory tract are the clinical hallmark present in nearly all patients. 2 In addition, up to 40% of the patients show gastrointestinal disease, concomitant lymphoproliferative disorders, autoimmune phenomena, or granulomatous inflammation. 2 The pathogenic understanding of antibody deficiency in humans has always been hampered by the great heterogeneity of the syndrome. 3 In 1966, Rosen and Janeway started to group antibody deficiencies by their mode of inheritance. 4 In 1973, Cooper included the clinical course and serum immunoglobulin levels, thereby separating hyper-IgM syndromes and selective IgA deficiency. 5 The remaining group of still very heterogeneous antibody deficiencies was termed CVID. Consecutive attempts to subclassify CVID by B-cell function in vitro 6,7 failed to reach diagnostic acceptance because of laborious and poorly standardized procedures and a lack of clinical relevance.In 2002, we and others suggested a flow cytometric classification of CVID according to the B-cell phenotype. 8,9 The abnormalities of circulating B cells in patients with CVID had already been recognized earlier, 10 but only with the ease and the broad availability of flow cytometry was a widespread and systematic analysis of these aberrations possible. The Freiburg classification divided patients into 3 groups by analyzing the expression of IgM, IgD, CD27 and CD21. 8 Group 1 was characterized by a severe reduction of switched memory B cells (IgD Ϫ IgM Ϫ CD27 ϩ less than 0.4% of lymphocytes), while group 2 representing 25% of the analyzed CVID patients exhibited nearly normal numbers of class-switched memory B cells, suggesting a post germinal center defect. The online version of this article contains a data supplement.The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked ''advertisement'' in accordance with 18 USC section 1734. Methods PatientsAll patients were diagnosed as having CVID based on the European Society for Immunodeficiencies/Pan-American Group for Immunodeficiency (ESID/PAGID) criteria, 11 including a marked decrease of IgG (at least 2 standard deviations [SDs] below the mean for age) and a marked decrease in at least one of the isotypes IgM or IgA, the onset of clinical significant immunodeficiency at greater than 2 years of age, and the exclusion of defined causes of hypogammaglobulinemia (see also www.esid.org). Not all patients have been evaluated for absent isohemagglutinins and/or poor response to vaccines. For the final evaluation of B-cell phenotyping, the following exclusion criteria were adopted: patients younger than 6 years of age at the time of flowcytometric evaluation, patients on immunosuppressive treatment, patients suffering currently from malignancies, and patients with less than 1% peripheral B cells. Altogether, 303 patients of origi...

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Combined decrease of defined B and T cell subsets in a group of common variable immunodeficiency patients

Cited by 52 publications

References 42 publications

Down Syndrome B-Lymphocyte Subpopulations, Intrinsic Defect or Decreased T-Lymphocyte Help

Down Syndrome B-Lymphocyte Subpopulations, Intrinsic Defect or Decreased T-Lymphocyte Help

CD4⁺CD25⁺Foxp3⁺ T regulatory cells, Th1 (CCR5, IL-2, IFN-γ) and Th2 (CCR4, IL-4, Il-13) type chemokine receptors and intracellular cytokines in children with common variable immunodeficiency

The EUROclass trial: defining subgroups in common variable immunodeficiency

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Combined decrease of defined B and T cell subsets in a group of common variable immunodeficiency patients

Cited by 52 publications

References 42 publications

Down Syndrome B-Lymphocyte Subpopulations, Intrinsic Defect or Decreased T-Lymphocyte Help

Down Syndrome B-Lymphocyte Subpopulations, Intrinsic Defect or Decreased T-Lymphocyte Help

CD4+CD25+Foxp3+ T regulatory cells, Th1 (CCR5, IL-2, IFN-γ) and Th2 (CCR4, IL-4, Il-13) type chemokine receptors and intracellular cytokines in children with common variable immunodeficiency

The EUROclass trial: defining subgroups in common variable immunodeficiency

Contact Info

Product

Resources

About

CD4⁺CD25⁺Foxp3⁺ T regulatory cells, Th1 (CCR5, IL-2, IFN-γ) and Th2 (CCR4, IL-4, Il-13) type chemokine receptors and intracellular cytokines in children with common variable immunodeficiency