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

Publisher: Informa Healthcare Country of Publication: England NLM ID: 8504629 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-4311 (Electronic) Linking ISSN: 08820139 NLM ISO Abbreviation: Immunol Invest Subsets: MEDLINE

Publication: London : Informa Healthcare
Original Publication: New York, N.Y. : M. Dekker, c1985-

Ataxia Telangiectasia/*epidemiology ; Immunologic Deficiency Syndromes/*epidemiology ; Respiratory Tract Infections/*epidemiology; Adolescent ; Adult ; Age of Onset ; Ataxia Telangiectasia/genetics ; Ataxia Telangiectasia Mutated Proteins/genetics ; Child ; Child, Preschool ; Female ; Humans ; Immunoglobulin Class Switching ; Immunologic Deficiency Syndromes/genetics ; Infant ; Iran/epidemiology ; Male ; Phenotype ; Respiratory Tract Infections/genetics ; Young Adult

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.

Keywords: ATM; Ataxia-telangiectasia; class switching recombination (CSR); hyper IgM syndrome; immune deficiency

EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins)

Date Created: 20200303 Date Completed: 20210930 Latest Revision: 20210930

20240829

10.1080/08820139.2020.1723104

32116070