Low numbers of regulatory T cells in common variable immunodeficiency: association with chronic inflammation<i>in vivo</i>

Fevang, Børre; Yndestad, Arne; Sandberg, Wiggo J.; Holm, Are Martin; Müller, Fredrik; Aukrust, Pål; Ss, Frøland

doi:10.1111/j.1365-2249.2006.03314.x

Cited by 94 publications

(72 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…There were no other significant associations with percentages of CD19, CD4, and CD8 cells and any other clinical phenotypes, though FOXP3 ϩ cells were not examined in this study. 42 There was an inverse correlation between IgG level at presentation and percentage of CD4 cells but not CD8 cells.…”

Section: Discussionmentioning

confidence: 93%

Common variable immunodeficiency disorders: division into distinct clinical phenotypes

Chapel

Lucas

Lee

et al. 2008

Blood

720

830

View full text Add to dashboard Cite

The European Common Variable Immunodeficiency Disorders registry was started in 1996 to define distinct clinical phenotypes and determine overlap within individual patients. A total of 7 centers contributed patient data, resulting in the largest cohort yet reported. Patients (334), validated for the diagnosis, were followed for an average of 25.6 years (9461 patientyears). Data were used to define 5 distinct clinical phenotypes: no complications, autoimmunity, polyclonal lymphocytic infiltration, enteropathy, and lymphoid malignancy. A total of 83% of patients had only one of these phenotypes. Analysis of mortality showed a considerable reduction in the last 15 years and that different phenotypes were associated with different survival times. Types of complications and clinical phenotypes varied significantly between countries, indicating the need for large, international registries. Ages at onset of symptoms and diagnosis were shown to have a Gaussian distribution, but were not useful predictors of phenotype. The only clinical predictor was polyclonal lymphocytic infiltration, which was associated with a 5-fold increased risk of lymphoid malignancy. There was widespread variation in the levels of serum immunoglobulin isotypes as well as in the percentages and absolute numbers of B cells, confirming the heterogeneity of these conditions. Higher serum IgM and lower circulating CD8 proportions were found to be predictive markers for polyclonal lymphocytic infiltration and autoimmunity, respectively. (Blood. 2008;112:277-286)

show abstract

Section: Discussionmentioning

confidence: 93%

Common variable immunodeficiency disorders: division into distinct clinical phenotypes

Chapel

Lucas

Lee

et al. 2008

Blood

720

830

View full text Add to dashboard Cite

show abstract

“…Clinically, a severe reduction in SMB is associated with a higher risk of granulomatous disease and splenomegaly (39), suggesting that a most profound lack of B cell maturation is likely to be associated with the abnormal cellular or cytokine environment that supports granuloma formation (20). CVID patients had significantly fewer Treg than controls, and a low frequency of Treg is clinically associated with splenomegaly (46,47), granulomatous disease (48), and autoimmune cytopenia (49). The suppressive function of Treg from CVID subjects with autoimmune disease is significantly attenuated compared to CVID subjects with no autoimmune disease and to healthy controls, and the expression of several proteins associated with Treg function (FoxP3, Granzyme A, XCL1, pSTAT5, and GITR) is decreased in the same patients (50).…”

Section: The Reduction Of Cd27+igd-igm-switched Memory B Cells (Smb) mentioning

confidence: 99%

Common variable immunodeficiency: Crossroads between infections, inflammation and autoimmunity

Baldovino

Montin

Martino

et al. 2013

Autoimmunity Reviews

View full text Add to dashboard Cite

“…Patients with CVID have a common feature in failure of B cell function, although a number of T cell abnormalities have been described, including reduced naive CD4 T cells [7], reduced proliferative responses to mitogens [8,9], reduced cytokine responses to mitogens and recall antigen [10,11] and reduced T regulatory cells (Tregs) [12][13][14] in selected patients. A subset of CVID patients are reported to have an increased susceptibility to recurrent viral infections or opportunistic infections that are more associated with T cell defects [7,15], particularly in those patients from consanguineous families [16], suggesting an unknown, autosomal recessive, combined immune deficiency.…”

Section: Introductionmentioning

confidence: 99%

T cell phenotypes in patients with common variable immunodeficiency disorders: associations with clinical phenotypes in comparison with other groups with recurrent infections

Bateman

Ayers

Sadler

et al. 2012

Clinical and Experimental Immunology

128

View full text Add to dashboard Cite

Summary Common variable immunodeficiency disorders (CVID) are a group of heterogeneous conditions that have in common primary failure of B cell function, although numerous T cell abnormalities have been described, including reduced proliferative response and reduced regulatory T cells. This study compared the T cell phenotype of CVID patients subdivided into clinical phenotypes as well as patients with partial antibody deficiencies [immunoglobulin (Ig)G subclass deficiency and selective IgA deficiency], X‐linked agammaglobulinaemia (XLA) and healthy and disease controls. Absolute numbers of T cell subpopulations were measured by four‐colour flow cytometry: naive T cells, central and effector memory and terminally differentiated (TEM) T cells, using CD45RA and CCR7 expression. Early, intermediate and late differentiation status of T cells was measured by CD27/CD28 expression. Putative follicular T cells, recent thymic emigrants and regulatory T cells were also assessed. Significant reduction in naive CD4 T cells, with reduced total CD4 and recent thymic emigrant numbers, was observed in CVID patients, most pronounced in those with autoimmune cytopenias or polyclonal lymphoproliferation. These findings suggest a lack of replenishment by new thymically derived cells. CD8 naive T cells were reduced in CVID patients, most significantly in the autoimmune cytopenia subgroup. There was a reduction in early differentiated CD4 and CD8 T cells and increased CD8 TEM in the CVID patients, particularly autoimmune cytopenia and polyclonal lymphoproliferation subgroups, suggesting a more activated T cell phenotype, due perhaps to an antigen‐driven process. XLA patients had significantly reduced putative follicular T cells, which may depend on B cells for survival, while no significant alterations were observed in the T cells of those with IgG subclass deficiency or selective IgA deficiency.

show abstract

Low numbers of regulatory T cells in common variable immunodeficiency: association with chronic inflammationin vivo

Abstract: Summary Common variable immunodeficiency (CVID) is

Cited by 94 publications

References 32 publications

Common variable immunodeficiency disorders: division into distinct clinical phenotypes

Common variable immunodeficiency disorders: division into distinct clinical phenotypes

Common variable immunodeficiency: Crossroads between infections, inflammation and autoimmunity

T cell phenotypes in patients with common variable immunodeficiency disorders: associations with clinical phenotypes in comparison with other groups with recurrent infections

Contact Info

Product

Resources

About