Anti-peptide Antibody Responses in Patients with Ataxia-telangiectasia

Document Type : Original Article


1 Student Research Committee, Alborz University of Medical Sciences, Alborz, Iran Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran

2 Uro-Oncology Research Center, Tehran University of Medical Sciences, Tehran, Iran

3 Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran


Background/Objectives: Ataxia-telangiectasia (AT) is a rare inherited disorder caused by mutations in the ATM (Ataxia Telangiectasia Mutated) gene. Antibody response to diphtheria and tetanus toxoid vaccines may reveal indirect information about both cellular and humoral arms of the immune system in these patients. This study, therefore, set out to assess the specific antibody responses against tetanus and diphtheria vaccination among AT patients.
Methods: Thirty-eight AT patients were entered the study and an appropriate questionnaire was completed for all of them. Laboratory findings including alpha fetoprotein, lymphocyte subsets, serum immunoglobulin levels of IgG, IgG subsets, IgA, IgM, IgE and antibody response against diphtheria and tetanus toxoids were measured.
Results: Thirty-eight A-T patients were enrolled in this study. Based on the anti-tetanus and anti-diphtheria antibody production, 24 and 14 patients were categorized in responder (R) and non-responder (NR) groups, respectively. Respiratory tract infection was the most common infectious complication reported more frequently in the R comparing to NR group. Within the non-infectious manifestations, after cerebellar ataxia, ocular telangiectasia (52.6%) and FTT (26.3%) were the most frequent. 34.8% of individuals in R group but none of the NR patients had normal serum immunoglobulin profile (P=0.015). Contrarily, HIGM phenotype was found more frequent in NR group comparing to R group (50% vs. 17.4%, p= 0.063).
Conclusions: In accordance with the previous studies, we observed sufficient antibody response to diphtheria and tetanus vaccines in most of the AT patients.


1. Gatti, R.A., et al., Localization of an ataxiatelangiectasia gene to chromosome 11q22-23. Nature, 1988. 336(6199):577-80. 2. Sanal, O., et al., Antibody response to a seven-valent pneumococcal conjugated vaccine in patients with ataxia-telangiectasia. J Clin Immunol, 2004. 24(4):411-7. 3. Ersoy, F., et al., Twenty-year follow-up of 160 patients with ataxia-telangiectasia. Turk J Pediatr, 1991. 33(4): p. 205-15. 4. Lefton-Greif, M.A., et al., Oropharyngeal dysphagia and aspiration in patients with ataxiatelangiectasia. J Pediatr, 2000. 136(2):225-31. 5. Chopra, C., et al., Immune deficiency in Ataxia-Telangiectasia: a longitudinal study of 44 patients. Clin Exp Immunol, 2014. 176(2):275-82. 6. Davies, E.G., Update on the management of the immunodeficiency in ataxia-telangiectasia. Expert Rev Clin Immunol, 2009. 5(5):565-75. 7. Schubert, R., J. Reichenbach, and S. Zielen, Deficiencies in CD4+ and CD8+ T cell subsets in ataxia telangiectasia. Clin Exp Immunol, 2002. 129(1):125-32. 8. Khanna, K.K., et al., Defective signaling through the B cell antigen receptor in Epstein-Barr virus-transformed ataxia-telangiectasia cells. J Biol Chem, 1997. 272(14): 9489-95. 9. Driessen, G.J., et al., Antibody deficiency in patients with ataxia telangiectasia is caused by disturbed B- and T-cell homeostasis and reduced immune repertoire diversity. J Allergy Clin Immunol, 2013. 131(5):1367-75.e9. 10. Sanal, O., et al., Impaired IgG antibody production to pneumococcal polysaccharides in patients with ataxia-telangiectasia. J Clin Immunol, 1999. 19(5):326-34. 11. Stray-Pedersen, A., et al., Pneumococcal conjugate vaccine followed by pneumococcal polysaccharide vaccine; immunogenicity in patients with ataxia-telangiectasia. Clin Exp Immunol, 2005. 140(3):507-16. 12. Conley, M.E., L.D. Notarangelo, and A. Etzioni, Diagnostic criteria for primary immunodeficiencies. Representing PAGID (PanAmerican Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies). Clin Immunol, 1999. 93(3):190-7. 13. Al-Herz, W., et al., Primary immunodeficiency diseases: an update on the classification from the international union of immunological societies expert committee for primary immunodeficiency. Front Immunol, 2011. 2:54. 14. Lumsden, J.M., et al., Immunoglobulinclass switch recombination is impaired in Atmdeficient mice. J Exp Med, 2004. 200(9):1111- 21. 15. Reina-San-Martin, B., et al., ATM is required for efficient recombination between immunoglobulin switch regions. J Exp Med, 2004. 200(9):1103-10. 16. Callen, E., et al., ATM prevents the persistence and propagation of chromosome breaks in lymphocytes. Cell, 2007. 130(1): p. 63-75. 17. Nowak-Wegrzyn, A., et al., Immunodeficiency and infections in ataxiatelangiectasia. J Pediatr, 2004. 144(4):505-11. 18. Mohammadinejad, P., et al., Class switch recombination process in ataxia telangiectasia patients with elevated serum levels of IgM. J Immunoassay Immunochem, 2015. 36(1): p. 16- 26. 19. Zaki-Dizaji, M., et al., Ataxia telangiectasia syndrome: moonlighting ATM. Expert Rev Clin Immunol, 2017. 13(12):1155-1172. 20. Ghiasy, S., et al., The clinical significance of complete class switching defect in Ataxia telangiectasia patients. Expert Rev Clin Immunol, 2017. 13(5):499-505. 21. Roifman, C.M. and E.W. Gelfand, Heterogeneity of the immunological deficiency in ataxia-telangiectasia: absence of a clinicalpathological correlation. Kroc Found Ser, 1985. 19:273-85. 22. Weemaes, C.M., et al., Antibody responses in vivo in chromosome instability syndromes with immunodeficiency. Clin Exp Immunol, 1984. 57(3):529-34. 23. Eisen, A.H., et al., IMMUNOLOGIC DEFICIENCY IN ATAXIA TELANGIECTASIA. N Engl J Med, 1965. 272:18-22. 24. Porro, M., et al., Immunogenic correlation between cross-reacting material (CRM197) produced by a mutant of Corynebacterium diphtheriae and diphtheria toxoid. J Infect Dis, 1980. 142(5):716-24. 25. Gupta, R.K., et al., Differences in the immunogenicity of native and formalinized cross reacting material (CRM197) of diphtheria toxin in mice and guinea pigs and their implications on the development and control of diphtheria vaccine based on CRMs. Vaccine, 1997. 15(12-13):1341-3. 26. Stray-Pedersen, A., et al., The impact of an early truncating founder ATM mutation on immunoglobulins, specific antibodies and lymphocyte populations in ataxia-telangiectasia patients and their parents. Clin Exp Immunol, 2004. 137(1):179-86. 27. Shelly, M.A., M.E. Pichichero, and J.J. Treanor, Low baseline antibody level to diphtheria is associated with poor response to conjugated pneumococcal vaccine in adults. Scand J Infect Dis, 2001. 33(7):542-4.