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


Amirifar P(1)(2), Mozdarani H(3), Yazdani R(2), Kiaei F(2), Moeini Shad T(2), Shahkarami S(2)(4), Abolhassani H(5)(6), Delavari S(2), Sohani M(2), Rezaei A(2), Hassanpour G(7), Akrami SM(1), Aghamohammadi A(2).
Author information:
(1)Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences , Tehran, Iran.
(2)Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, University of Medical Science , Tehran, Iran.
(3)Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University , Terhran, Iran.
(4)Medical Genetics Network
(Megene), Universal Scientific Education and Research Network
(USERN) , Tehran, Iran.
(5)Research Center for Primary Immunodeficiencies, Iran University of Medical Sciences , Tehran, Iran.
(6)Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge , Stockholm, Sweden.
(7)Center for Research of Endemic Parasites of Iran, Tehran University of Medical Sciences , Tehran, Iran.


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.