Misclassification of Ataxia Telangiectasia with Hyper IgM immune profile

Document Type: Case Report

Authors

1 Department of Allergy and Clinical Immunology, Department of Pediatrics, Pediatrics Center of Excellence, Children's Medical Center, Tehran, University of Medical Sciences, Tehran, Iran

2 Pediatric Rheumatology Research Group, Rheumatology Research Center, Tehran University of Medical Science, Tehran, Iran

3 Department of Allergy and Clinical Immunology, Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Ataxia-telangiectasia is a rare primary immunodeficiency and multisystem DNA repair disorder which is caused by mutation in ataxia telangiectasia mutated (ATM) gene. The ATM protein plays a critical role in sensing DNA double-strand breaks (DSB), oxidative stress and other genetic stresses. The ATM can directly mention DNA ends in repair complexes and directly involved in the repair of DSBs induced during T cell and B cell rearrangement. Therefore, increase serum IgM level and recurrent infection mainly sinopulmonary, indistinguishable from hyper IgM syndrome can be a presentation of some AT patients. AT patients with class-switched defect are more prone to severe infections, autoimmunity and lymphoproliferative disorders. Herein we present an AT patient with characteristic feature of hyper IgM phenotype and lymphoproliferation.

Keywords


1. Amirifar, P., et al., Ataxia-telangiectasia: A review of clinical features and molecular pathology. 2019. 30(3): p. 277-288. 2. Shiloh, Y., ATM and related protein kinases: safeguarding genome integrity. Nat Rev Cancer, 2003. 3(3): p. 155-68. 3. Reina-San-Martin, B., et al., ATM is required for efficient recombination between immunoglobulin switch regions. J Exp Med, 2004. 200(9): p. 1103-10. 4. Notarangelo, L.D., et al., Defects of classswitch recombination. Journal of Allergy and Clinical Immunology, 2006. 117(4): p. 855-864. 5. Qamar, N. and R.L. Fuleihan, The hyper IgM syndromes. Clinical reviews in allergy & immunology, 2014. 46(2): p. 120-130. 6. Reina-San-Martin, B., et al., ATM is required for efficient recombination between immunoglobulin switch regions. Journal of Experimental Medicine, 2004. 200(9): p. 1103- 1110. 7. Mohammadinejad, P., et al., Class switch recombination process in ataxia telangiectasia patients with elevated serum levels of IgM. Journal of Immunoassay and Immunochemistry, 2015. 36(1): p. 16-26. 8. Lumsden, J.M., et al., Immunoglobulin class switch recombination is impaired in Atmdeficient mice. Journal of Experimental Medicine, 2004. 200(9): p. 1111-1121. 9. Rothblum-Oviatt, C., et al., Ataxia telangiectasia: a review. Orphanet journal of rare diseases, 2016. 11(1): p. 159. 10. Noordzij, J.G., et al., Ataxia–telangiectasia patients presenting with hyper-IgM syndrome. Archives of disease in childhood, 2009. 94(6): p. 448-449. 11. Ghiasy, S., et al., The clinical significance of complete class switching defect in Ataxia telangiectasia patients. Expert review of clinical immunology, 2017. 13(5): p. 499-505. 12. Van Os, N.J., et al., Ataxia-telangiectasia: immunodeficiency and survival. Clinical Immunology, 2017. 178: p. 45-55. 13. Suarez, F., et al., Incidence, presentation, and prognosis of malignancies in ataxiatelangiectasia: a report from the French national registry of primary immune deficiencies. J Clin Oncol, 2015. 33(2): p. 202-8.14. Azizi, G., et al., Autoimmunity in primary Tcell immunodeficiencies. Expert review of clinical immunology, 2016. 12(9): p. 989-1006.