Effect of Class Switch Recombination Defect on the Phenotype of Ataxia-Telangiectasia Patients. (17th February 2021)

• Record Type: Journal Article
• Authors: Amirifar, Parisa; Mozdarani, Hossein; Yazdani, Reza; Kiaei, Fatemeh; Moeini Shad, Tannaz; Shahkarami, Sepideh; Abolhassani, Hassan; Delavari, Samaneh; Sohani, Mahsa; Rezaei, Arezou; Hassanpour, Gholamreza; Akrami, Seyed Mohammad; Aghamohammadi, Asghar
• Is Part Of: Immunological investigations. Volume 50:Number 2/3(2021)
• Page Start: 201
• Page End: 215
• Publication Date: 2021-02-17
• Subjects: Ataxia-telangiectasia -- ATM -- immune deficiency -- class switching recombination (CSR) -- hyper IgM syndrome; Immunology -- Periodicals; Immunochemistry -- Periodicals; Cellular immunity -- Periodicals; Communicable diseases -- Periodicals; 616.079
• DOI: 10.1080/08820139.2020.1723104
• Languages: English
• ISSNs: 0882-0139

Abstract

ABSTRACT: Objectives : Ataxia-telangiectasia (A-T) is an autosomal recessive neurodegenerative disorder with multisystem involvement caused by homozygous or compound heterozygous mutations in the ataxia telangiectasia mutated (ATM) gene which encodes a serine/threonine protein kinase. The aims of this study were to investigate class switch recombination (CSR) and to review the clinical and immunologic phenotypes of 3 groups of A-T patients, including A-T patients with CSR defects (CSR-D), A-T patients with selective immunoglobulin A deficiency (IgA-D) and A-T patients with normal Ig level. Methods : In this study, 41 patients with confirmed diagnosis of A-T (16 A-T patients with HIgM, 15 A-T patients with IgA-D, and 10 A-T patients with normal Ig levels) from Iranian immunodeficiency registry center were enrolled. B-cell proliferation, in vitro CSR toward IgE and IgA were compared between three groups as well as G2 radiosensitivity assay. Results : Earliest presentation of telangiectasia was a significant hallmark in A-T patients with CSR-D ( p = .036). In this investigation, we found that the frequency of respiratory infection ( p = .002), pneumonia ( p = .02), otitis media ( p = .008), chronic fever ( p < .001), autoimmunity ( p = .02) and hepatosplenomegaly ( p = .03) in A-T patients with HIgM phenotype were significantly higher than the other groups. As expected IgE production stimulation and IgA CSR were perturbed in HIgM patients that were aligned with the higher readiosenstivity scores in this group. Conclusion : A-T patients with HIgM compared to other A-T patients presenting more infections and noninfectious complications, therefore, early detection and careful management of these patients is necessary.