Decrease in phenotypic regulatory T cells in subsets of patients with common variable immunodeficiency (original) (raw)
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A Decreased Frequency of Regulatory T Cells in Patients with Common Variable Immunodeficiency
PLoS ONE, 2009
Introduction: Common variable immunodeficiency disorder (CVID) is a heterogeneous syndrome, characterized by deficient antibody production and recurrent bacterial infections in addition abnormalities in T cells. CD4 + CD25 high regulatory T cells (Treg) are essential modulators of immune responses, including down-modulation of immune response to pathogens, allergens, cancer cells and self-antigens.
Allergologia et Immunopathologia, 2009
Background: A system based on the B-cell phenotype has recently been proposed to classify patients suffering from common variable immunodefi ciency (CVID). Immunophenotypic T-cell abnormalities have also been correlated with clinical fi ndings, although they have never been used in classifi cation strategies. Objective: To simultaneously assess T and B-cell subset abnormalities in CVID patients and their relationship with clinical fi ndings. To identify potential immunophenotypic T-cell abnormalities that could be further evaluated in multicenter studies. Patients and Methods: Peripheral blood lymphocytes from 21 CVID patients and 21 healthy donors were stained for T and B-cell subsets, analyzed by fl ow cytometry, and correlated with clinical characteristics. Results: Patients classifi ed as MB0 (CD19/CD27+ < 11 %) showed higher percentages of CD4/ CD45RA-(87 % vs 67 %, p = 0.028) and lower percentages of CD8/CD45RA+CCR7+ (10 % vs 26 %, p = 0.028) and CD4/CD25+ T-cells (36 % vs 62 %, p = 0.034) than MB2 patients. Even though our cohort was small, we observed a higher prevalence of distinct clinical complications of CVID in patients with B and T-cell abnormalities. Nonmalignant lymphoproliferative disorders and IgG hypercatabolism were more frequently observed in MB0 patients. A higher prevalence of splenomegaly was observed among CVID patients with increased levels of CD4/CD45RA-, activated CD4/CD38+DR+, CD8/DR+, and CD8/CD38+ T-cells, as well as in those with lower percentages of CD4/CD45RA+CCR7+ and CD4/CD25+ T-cells. Lymphoproliferative disorders were more prevalent among CVID patients with higher CD4/CD45RA-percentages. Conclusion: The study of T-cell subsets warrants further evaluation as a potential tool to better identify CVID patients with distinct clinical profi les.
Iranian Journal of Allergy Asthma and Immunology, 2014
Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder characterized by a greatly increased susceptibility to severe fungal and bacterial infections caused by defects in NADPH oxidase of phagocytic cells. We aimed to investigate immunophenotype alterations of naïve and memory B cells and B1a cells in peripheral whole blood from Iranian patients with CGD.
Cellular Immunology, 2013
Common variable immunodeficiency (CVID) is one of the predominant antibody disorders where abnormalities in regulatory T cells (Tregs) may result in autoimmunity and chronic inflammation. To evaluate Tegs frequency and function, 13 CVID patients and 10 age-and sex-matched healthy volunteer were enrolled. The percentages of Tregs were calculated using flow cytomety method. For assessment of Treg function, Tregs were isolated and their suppressive functions were determined using Tregs suppression assay. The levels of immunoregulatory cytokines IL-10 and TGF-b produced by Tregs were also measured. Our results revealed that Tregs frequency (P < 0.001) and their suppressive functions (P < 0.001) were impaired in CVID patients. The level of TGF-b did not differ between CVID patients and controls (p = 0.09); while the amount of IL-10 was remarkably decreased in CVID patients (P = 0.007). Our findings suggest that disturbed Tregs frequency and their functional characteristics might account for aberrant immune responses observed in CVID patients.
Scandinavian Journal of Immunology, 2013
Common variable immunodeficiency (CVID) is the most symptomatic primary antibody deficiency associated with recurrent infections and chronic inflammatory diseases as well as autoimmunity. CD4 + CD25 + FOXP3 + regulatory T cells (Tregs) are critical T cell subsets for maintaining self-tolerance and regulation of immune response to antigens thus play a pivotal role in preventing autoimmunity. Thirtyseven CVID patients and 18 age-/sex-matched controls were enrolled. Peripheral blood mononuclear cells (PBMCs) were obtained from both groups, and the percentage of Tregs was calculated using flow cytometry method. The mRNA expression of Tregs' surface markers cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and glucocorticoid-induced tumour necrosis factor receptor (GITR), which are associated with Tregs' inhibitory function, was compared between patients and controls by quantitative real-time PCR TaqMan method. The results revealed that the frequency of Tregs was significantly lower in CVID patients than normal individuals (P < 0.001). In addition, CVID patients with autoimmunity were found to have markedly reduced proportion of Tregs compared to those cases without autoimmune diseases (P = 0.023). A significant difference was seen in factor forkhead box P3 (FOXP3) expression between CVID patients and controls (P < 0.001). The mRNAs of CTLA-4 and GITR genes were expressed at lower levels in CVID patients compared to control group (P = 0.005 and <0.001, respectively). Our findings showed reduced proportion of Tregs in CVID patients together with downregulation of FOXP3 protein and diminished expression of inhibitory Tregs' markers. It could be concluded that all of these changes may be responsible for cellular immune dysregulation observed in these patients especially those with autoimmune manifestation.
Clinical immunology (Orlando, Fla.), 2009
Approximately 25% of subjects with common variable immunodeficiency (CVID) develop autoimmune disease. We analyzed Tcell subsets, specifically regulatory Tcells along with B cell subsets to determine whether there were changes in regulatory T cells which would correlate with the autoimmune disease clinical phenotype in CVID subjects. We hypothesized that regulatory T cell (CD4 + CD25hiCD127lo) suppressive function would be impaired in CVID subjects with autoimmune disease. Using purified, sorted Treg from CVID subjects (n = 14) and from healthy controls (HC, n = 5) in standard suppression assays, we found the suppressive function of Treg from CVID subjects with autoimmune disease (CVID w/ AI, n = 8) to be significantly attenuated compared to CVID subjects with no autoimmune disease (CVID w/o AI, n = 6) and to HC (n = 5). A number of proteins associated with Treg function were decreased in expression as detected through immunofluorescent antibody via flow cytometry (mean fluorescence intensity (MFI) of FoxP3, Granzyme A, XCL1, pSTAT5, and GITR in Treg was significantly lower (by up to 3 fold) in CVID w/ AI compared to CVID w/o AI and HC. Furthermore, a statistically significant correlation was found between intracellular MFI of FoxP3, Granzyme A, and pSTAT5 in Treg and the degree of Treg dysfunction. These results suggest that attenuation of Treg function is associated with autoimmune disease in CVID subjects and may contribute to autoimmune pathogenesis. ava i l a b l e a t w w w. s c i e n c e d i r e c t . c o m w w w. e l s ev i e r. c o m / l o c a t e / yc l i m Clinical Immunology (2009) 131, 240-253
Clinical Immunology, 2006
Common variable immunodeficiency disease (CVID) is a primary immune disorder affecting B cells and characterized by hypogammaglobulinemia and recurrent infections. To elucidate the clinical and immunological heterogeneity of this condition, we have studied B and T cell subsets in 25 CVID patients. In eleven of them, we observed a remarkable relative expansion of a B cell subpopulation (CD19 hi /CD21 lo cells) characterized by the absence of CD23 and the reduced expression of the chemokine receptors CXCR5 and CCR7. Our analyses demonstrated in these patients that the expansion of CD19 hi /CD21 lo cells correlates with a selective decrease of circulating naRve and CD21 hi memory B lymphocytes. The same group of patients displayed a simultaneous severe reduction of naRve CD4+ T cells associated with decreased levels of T cell receptor excision circles. These observations suggest that a combined defect in generation of B and T subpopulations may account for the abnormal immunophenotype characterizing this subgroup of CVID patients. D a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m w w w . e l s e v i e r . c o m / l o c a t e / y c l i m
Utility of peripheral blood B cell subsets analysis in common variable immunodeficiency
Clinical and Experimental Immunology, 2012
Summary Abnormalities in peripheral blood B cell subsets have been identified in common variable immunodeficiency (CVID) patients and classification systems based upon their numbers have been proposed to predict the clinical features. We analysed B lymphocyte subsets by multi-colour flow cytometry (MFC) in a cohort of well-characterized CVID patients to look at their clinical relevance and validate the published association of different classification criteria (Freiburg, Paris and Euroclass) with clinical manifestations. CVID patients had a reduced proportion of total and switched memory B cells (MBC, swMBC) compared to normal controls (P < 0·0006). Patients classified in Freiburg Ia had a higher prevalence of granulomatous diseases (P = 0·0034). The previously published associations with autoimmune diseases could not be confirmed. The Euroclass classification was not predictive of clinical phenotypes. The absolute numbers of all B cell subsets were reduced in CVID patients compa...
ISRN Immunology, 2013
Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by the failure of B lymphocytes differentiation leading to deficient immunoglobulins secretion. The identified genetic defects account only for a minority of cases. The importance of B cells immunophenotyping in the classification of CVID is known. This procedure can identify alterations on the cell surface molecules expression that could explain some immunological disorders characteristic of CVID. Moreover, some immunophenotypical aspects can correlate with clinical features of the disease. We used this procedure to analyze a cohort of 23 patients affected by CVID, in order to identify the novel alterations of B cells and to find the possible correlations with clinical features. Circulating B cells were studied by flow cytometry incubating whole blood with specific antibodies for B cell surface molecules including CD27, IgM, IgD, CD21, and CD23. We compared the population of "switched memory" IgD− CD27+ B lymphocytes with the population of "switched memory" IgM− IgD− CD23− CD27+ B cells. These last B cells were reduced in patients compared to healthy controls; moreover, IgM− IgD− CD23− CD27+ B cells were lower than IgD− CD27+ B cells in patients with CVID. The reduction of this subset of B lymphocytes correlates more tightly than IgD− CD27+ B cells with lymphadenopathy and airways infections. In conclusion, our findings may help in better identifying patients with CVID.