CVID patients with autoimmunity have elevated T cell expression of granzyme B and HLA-DR and reduced levels of Treg cells

Carter, Clive R. D.; Aravind, Ganesha; Smalle, Natuley; Cole, June Y.; Savic, Sinisa; Wood, Philip

doi:10.1136/jclinpath-2012-201046

Cited by 43 publications

(29 citation statements)

References 33 publications

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“…Marked expansion of activated CD8 + T cells has also been reported in CVID patients [68,69]. It has been demonstrated that CD8…”

Section: Cd8 T-cell Defects In Cvidmentioning

confidence: 79%

“…+ T cells, CD8 + T cells are deficient in CVID patients: levels of both naive and effector memory CD8 + T cells are reduced [13], although levels of activated CD8 + T cells are increased [43,68]. Bateman et al [13] reported that the reduction in naive CD8 + T-cell counts was more significant in CVID patients with autoimmune cytopenia [13].…”

Section: Cd8 T-cell Defects In Cvidmentioning

confidence: 99%

“…Moreover, CVID patients with activated CD8 + T cells showed reduced diversity in their TCR repertoire that was more severe in CVID patients with the above-mentioned complications [69]. In addition to HLA-DR, CD8 + T cells from CVID patients with autoimmunity have higher expression levels of granzyme B [68]. Moreover, CD8…”

Section: Cd8 T-cell Defects In Cvidmentioning

confidence: 99%

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T-Cell Abnormalities in Common Variable Immunodeficiency

Azizi

Rezaei

Kiaee

et al. 2016

J Investig Allergol Clin Immunol

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Common variable immunodeficiency (CVID) is the most common clinical primary immunodeficiency. It is characterized by a defect in B-cell differentiation to plasma and memory B cells. Moreover, numerous T-cell abnormalities have been reported and include decreased T-cell count and proliferative response, increased T-cell activation and apoptosis, and abnormalities in cytokine production. The aims of this review are to describe phenotypic and functional defects in T cells in CVID patients and to review the literature with respect to the effects of immunoglobulin replacement on the T-cell component in CVID patients. Key words: Common variable immunodeficiency. T cell. Helper T cells. Regulatory T cells. ResumenLa inmunodeficiencia común variable (CVID) es la inmunodeficiencia primaria más frecuente. Se caracteriza por un defecto en la diferenciación de linfocitos B hacia células plasmáticas y linfocitos B memoria. Se han descrito numerosas alteraciones en los linfocitos T de estos pacientes, tales como disminución en el número de linfocitos T y en sus respuestas proliferativas, aumento en la activación de células T y en la apoptosis, así como alteraciones en la producción de citokinas. El objetivo de esta revisión es describir las alteraciones funcionales y fenotípicas de los linfocitos T en los pacientes con CVID y revisar la bibliografía en relación a los efectos que la administración de inmunoglobulinas produce en los linfocitos T de los pacientes con CVID. Palabras clave: Inmunodeficiencia común variable. Células T. Células T helper. Células T reguladoras.

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“…Marked expansion of activated CD8 + T cells has also been reported in CVID patients [68,69]. It has been demonstrated that CD8…”

Section: Cd8 T-cell Defects In Cvidmentioning

confidence: 79%

Section: Cd8 T-cell Defects In Cvidmentioning

confidence: 99%

See 1 more Smart Citation

T-Cell Abnormalities in Common Variable Immunodeficiency

Azizi

Rezaei

Kiaee

et al. 2016

J Investig Allergol Clin Immunol

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“…34 Interestingly, although common variable immunodeficiency is thought to be primarily a B-cell disorder, 20% of patients present with autoimmune syndromes, which is hypothesized to be due to reduced regulatory T cells and consequently elevated levels of activated T cells. 35 T cells are thought to have a pivotal role in chronic autoimmune diseases and their dysfunction may be responsible for autoimmune enteropathy. In fact, tacrolimus, an effective agent in the treatment of autoimmune enteropathy, exerts its immunosuppressive effects by primarily interfering with T-cell activation.…”

Section: Discussionmentioning

confidence: 99%

Pediatric autoimmune enteropathy: an entity frequently associated with immunodeficiency disorders

et al. 2014

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The term pediatric autoimmune enteropathy was originally applied to a form of intractable diarrhea seen in children under the age of 6 months and characterized by male predominance, concurrent autoimmuneassociated disorders, circulating gut autoantibodies, a lack of severe immunodeficiency and small bowel atrophy with prominent crypt apoptosis. However, recent studies have cast doubt over the specific clinicopathologic findings associated with this entity. We, therefore, collected 178 gastrointestinal biopsies from 14 patients and examined their clinical, serologic and pathologic findings. Patients at presentation ranged in age from birth to 15.9 years (median, 5.5 months; mean, 4.1 years) and included six males and eight females. All children suffered from chronic watery diarrhea and malnutrition. Concomitant-associated disorders were noted in 11 (79%) cases and included 10 (71%) with an immunodeficiency disorder and/or another autoimmunerelated disease. Eleven patients (79%) were positive for anti-enterocyte antibodies. The salient findings of autoimmune enteropathy were most prominent in the small intestines and the majority (79%) of patients demonstrated villous blunting, crypt hyperplasia, mononuclear cell inflammatory expansion of the lamina propria and crypt apoptosis. The remaining (21%) patients showed marked intraepithelial lymphocytosis reminiscent of celiac disease. Further, acute cryptitis and crypt abscesses were seen in seven (50%) patients obscuring the presence of apoptosis. The absence of Paneth cells, goblet cells or both was noted in seven (50%) patients. Follow-up information was available for all patients with 13 (93%) receiving immunosuppressant therapy and demonstrating partial-to-complete response. In total, three patients died from continued diarrhea and sepsis with one decedent before treatment could be initiated. In summary, autoimmune enteropathy in children is a heterogenous disease with protean clinical and pathologic findings. Although anti-enterocyte antibodies were identified in the majority of the cases, their presence was variable and insensitive. In addition, pediatric autoimmune enteropathy was frequently encountered in the setting of immunodeficiency disorders.

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“…Several studies report that Treg frequency and their functional characteristics are disturbed and might account for aberrant immune responses observed in CVID patients [39,81,82,83]. These abnormalities in Tregs may result in elevated levels of activated T cells, autoimmunity, and chronic inflammation [39,81].…”

Section: Autoimmunity In Padsmentioning

confidence: 99%

Autoimmunity in Primary Antibody Deficiencies

Azizi¹,

Ahmadi²,

Abolhassani³

et al. 2016

Int Arch Allergy Immunol

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Primary antibody deficiencies (PADs) are the most common inherited primary immunodeficiencies in humans, characterized by hypogammaglobulinemia, an inability to produce specific antibodies, and recurrent infections mainly caused by encapsulated bacteria. However, it has been shown that inflammatory disorders, granulomatous lesions, lymphoproliferative diseases, cancer, and autoimmunity are associated with the various types of PAD. Both systemic and organ-specific autoimmune diseases could be attributed to B-cell defects in PAD patients. Immune thrombocytopenic purpura and autoimmune hemolytic anemia are the most common autoimmune disorders in this group of patients. The aim of this review is to describe the proposed mechanisms for autoimmunity and to review the literature with respect to the reported autoimmune disorders in each type of PAD.

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CVID patients with autoimmunity have elevated T cell expression of granzyme B and HLA-DR and reduced levels of Treg cells

Abstract: These results highlight that reduced levels of Treg cells were associated with elevated levels of activated T cells, suggesting that reduced Treg cells in these patients may have functional consequences in allowing exaggerated T cell responses.

Cited by 43 publications

References 33 publications

T-Cell Abnormalities in Common Variable Immunodeficiency

T-Cell Abnormalities in Common Variable Immunodeficiency

Pediatric autoimmune enteropathy: an entity frequently associated with immunodeficiency disorders

Autoimmunity in Primary Antibody Deficiencies

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