Effect of Class Switch Recombination Defect on the Phenotype of Ataxia-Telangiectasia Patients

Amirifar, Parisa; Mozdarani, Hossein; Yazdani, Reza; Kiaei, Fatemeh; Shad, Tannaz Moeini; Shahkarami, Sepideh; Abolhassani, Hassan; Delavari, Samaneh; Sohani, Mahsa; Rezaei, Arezou; Hassanpour, Gholamreza; Akrami, Seyed Mohammad; Aghamohammadi, Asghar

doi:10.1080/08820139.2020.1723104

Cited by 24 publications

(28 citation statements)

References 52 publications

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“…The ATM kinase plays an important role in the processes of lymphocyte development and acquirement of immunocompetence, which rely on its function of DNA double-strand break repair in course of the V(D)J recombination. The pathophysiology of successful lymphocyte antigen receptor genes rearrangement and class switch recombination (CSR) of immunoglobulin genes are therefore critically important ATM kinase functions (5)(6)(7). Disturbed B and T cell homeostasis and failure of immunosurveillance are significant contributors to the development of autoimmune and autoinflammatory disorders, organ-specific pathology, and lymphoproliferation in A-T affected children.…”

Section: Introductionmentioning

confidence: 99%

Granulomatous Liver Disease in Ataxia-Telangiectasia With the Hyper-IgM Phenotype: A Case Report

2020

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Ataxia-telangiectasia (A-T) is an autosomal recessive disorder characterized by neurodegeneration, combined immunodeficiency, and oculocutaneous telangiectasia. The hyper-IgM phenotype of AT , correlating with a class-switch recombination defect, IgG and IgA deficiency, T helper and B cell lymphopenia, immune dysregulation, proinflammatory immune response, autoimmune disease, and a high risk of lymphomagenesis. Progressive liver disease is a hallmark of classical AT with the hyper-IgM phenotype and manifests as non-alcoholic hepatic steatosis and fibrosis. We report a case of a 17-year-old male AT patient, in whom a progressive granulomatous liver disease with portal hypertension, has led to massive splenomegaly and hypersplenism, metabolic liver insufficiency, bleeding from esophageal varices and pancytopenia. In this patient, an unusual severe disease course with a highly variable constellation of AT symptomatology includes granulomatous skin, visceral, and internal organs disease with liver involvement. The liver disease is associated with the hyper-IgM immunophenotype and escalating neurodegeneration, creating a vicious circle of immune deficiency, permanent systemic inflammatory response, and organ-specific immunopathology.

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Section: Introductionmentioning

confidence: 99%

Granulomatous Liver Disease in Ataxia-Telangiectasia With the Hyper-IgM Phenotype: A Case Report

2020

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“…Up to 10% of the patients with A-T have decreased IgA with normal to increased IgM levels, designated as a hyper-IgM (HIGM) phenotype [ 17 ]. This phenotype has shown a strongly reduced life expectancy in patients with A-T [ 18 , 19 ]. In these subgroups, respiratory failure is a common cause of death [ 3 , 19 ], with almost all patients developing recurrent upper and lower respiratory infections and chronic lung disease early in life [ 18 , 19 ].…”

Section: Discussionmentioning

confidence: 99%

“…This phenotype has shown a strongly reduced life expectancy in patients with A-T [ 18 , 19 ]. In these subgroups, respiratory failure is a common cause of death [ 3 , 19 ], with almost all patients developing recurrent upper and lower respiratory infections and chronic lung disease early in life [ 18 , 19 ]. Lymphoproliferative disorders are also more common among patients with A-T with an HIGM profile, reflecting immune dysregulation [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

The Role of Respiratory Viruses in Children with Ataxia-Telangiectasia

Méndez-Echevarría

Caminoa

Rabes

et al. 2021

Viruses

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Background: The impact of respiratory virus infection in patients diagnosed with ataxia-telangiectasia (A-T) has not been well studied. Methods: A prospective case control study was performed at a National Reference Unit for Primary Immunodeficiency in Spain (from November 2018 to July 2019), including patients younger than 20 years. Symptom questionnaires and nasopharyngeal swabs from multiple respiratory viruses’ polymerase chain reaction were collected monthly, and between visits in case of symptoms. Results: Twenty-two individuals were included (11 patients; 11 controls); 164 samples were obtained (81 patients; 84 controls). Patients presented respiratory symptoms more frequently compared with controls (26.5% vs. 3.5%; p < 0.01). Viral detection was observed in 23 (27.3%) episodes in patients and in 15 (17.8%) episodes in controls (p = 0.1). Rhinovirus was the most frequent virus in patients and controls (60% and 53.3%, respectively). Episodes with positive viral detection had associated symptoms in 54% of patients and 18% of controls (p = 0.07). However, patients with A-T presented a similar rate of symptoms during episodes with positive and negative viral detection (26% vs. 27%). The median points given for each questionnaire during symptomatic episodes with negative viral detection were 13/23 points, and during symptomatic positive detection, 7.5/23 points (p = 0.1). In the control group, all but two were asymptomatic during positive viral episodes (score: 2/23 and 3/23 points). Symptomatic episodes, with either positive or negative viral detection, were associated with lower IgA and higher IgM titers and higher CD8+ counts (p < 0.05), particularly when these episodes were moderate/severe. Conclusions: Patients with A-T more frequently present symptomatic viral infections than controls, especially those with lower IgA and higher IgM titers and higher CD8+ counts.

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“…1,2,11 These clinical complications play indispensable role in the morbidity and mortality of the disease. 6 In the present study, we investigated a child with A-T who had recurrent hospital admission due to repetitive infections, hematologic disorders, and neurological problems. Previous studies have indicated that some clinical complications are mediated by immune disorders in A-T patients.…”

Section: Case Historymentioning

confidence: 99%

Clinical complications and their management in a child with ataxia‐telangiectasia (A‐T): A case report study

Arani

ArefNezhad

Fathgharib

et al. 2020

Clinical Case Reports

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Effect of Class Switch Recombination Defect on the Phenotype of Ataxia-Telangiectasia Patients

Cited by 24 publications

References 52 publications

Granulomatous Liver Disease in Ataxia-Telangiectasia With the Hyper-IgM Phenotype: A Case Report

Granulomatous Liver Disease in Ataxia-Telangiectasia With the Hyper-IgM Phenotype: A Case Report

The Role of Respiratory Viruses in Children with Ataxia-Telangiectasia

Clinical complications and their management in a child with ataxia‐telangiectasia (A‐T): A case report study

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