Exons Analysis of Interferon-Gamma Receptor 1 Gene in Patients with Mendelian Susceptibility to Mycobacterial Diseases (MSMD) in the Central Region of Iran

Document Type : Original Article (s)

Authors

1 Professor, Acquired Immunodeficiency Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

2 PhD in Laboratory Sciences, Infectious Diseases and Tropical Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

3 PhD Candidate, Acquired Immunodeficiency Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

4 Nosocomial Infection Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

5 Assistant Professor, Department of Pediatrics, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

6 PhD in Molecular Medicine, Acquired Immunodeficiency Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

7 Medical Genetics Laboratory, Alzahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran

8 PhD in Microbiology, Infectious Diseases and Tropical Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

9 Acquired Immunodeficiency Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

10 General Practitioner, Molahadi Sabzevari Health Center, Isfahan University of Medical Sciences, Isfahan, Iran

11 Associate Professor, Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

12 General Practitioner, Department of Disease Control, Provincial Health Center, Isfahan University of Medical Sciences, Isfahan, Iran

13 General Practitioner, PhD in Molecular Medicine, Acquired Immunodeficiency Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Mendelian susceptibility to mycobacterial diseases (MSMD) is a rare immunodeficiency disease which is caused by interferon-gamma (IFN-γ) signaling impairment. Patients with MSMD are susceptible to infections with weakly virulent non-tuberculous mycobacteria (NTM) and the Bacillus Calmette-Guérin (BCG) vaccine strain. Regarding that a great number of identified mutations in MSMD are located on IFN-γ receptor 1 (IFNGR1) gene, this study aimed to evaluate IFNGR1 mutation in patients with MSMD in the central region of Iran.Methods: We examined 31 patients suspected to MSMD based on defined criteria. IFNGR1 gene mutation analysis was performed on the DNA samples using polymerase chain reaction (PCR) and gene sequencing methods.Findings: The sequencing of exons 1-6 of IFNGR1 gene in patients with MSMD was evaluated, and among 31 patients, six polymorphisms were found, that two of them were not reported before.Conclusion: In this research, two polymorphisms were found in exon 1, rs17181457 and rs2234711, both of them increase the susceptibility to mycobacterial infection. The approach to treatment of infection in patients with MSMD is based on the kind of mutation. Therefore, assessment of gene mutation in these patients is helpful to choose the appropriate treatment.

Keywords

References

  1. Al-Muhsen S, Casanova JL. The genetic heterogeneity of mendelian susceptibility to mycobacterial diseases. J Allergy Clin Immunol 2008; 122(6): 1043-51.
  2. Stenger S, Modlin RL. T cell mediated immunity to Mycobacterium tuberculosis. Curr Opin Microbiol 1999; 2(1): 89-93.
  3. Hadifar S, Moghim S, Gasemian-Safaei H, Fazeli H, Farid F, Moghoofei M, et al. Identification of non-tuberculosis mycobacteria isolates by polymerase chain reaction-restriction enzyme analysis of 360-bp fragment of rpoB gene. J Isfahan Med Sch 2014; 31(266): 2131-8. [In Persian].
  4. Holland SM. Treatment of infections in the patient with Mendelian susceptibility to mycobacterial infection. Microbes Infect 2000; 2(13): 1579-90.
  5. Holland SM. Immunotherapy of mycobacterial infections. Semin Respir Infect 2001; 16(1): 47-59.
  6. Bustamante J, Boisson-Dupuis S, Abel L, Casanova JL. Mendelian susceptibility to mycobacterial disease: genetic, immunological, and clinical features of inborn errors of IFN-gamma immunity. Semin Immunol 2014; 26(6): 454-70.
  7. Jouanguy E, Altare F, Lamhamedi S, Revy P, Emile JF, Newport M, et al. Interferon-gamma-receptor deficiency in an infant with fatal bacille Calmette-Guerin infection. N Engl J Med 1996; 335(26): 1956-61.
  8. Newport MJ, Huxley CM, Huston S, Hawrylowicz CM, Oostra BA, Williamson R, et al. A mutation in the interferon-gamma-receptor gene and susceptibility to mycobacterial infection. N Engl J Med 1996; 335(26): 1941-9.
  9. van de Vosse E, van Dissel JT. IFN-gammaR1 defects: Mutation update and description of the IFNGR1 variation database. Hum Mutat 2017; 38(10): 1286-96.
  10. Jouanguy E, Dupuis S, Pallier A, Doffinger R, Fondaneche MC, Fieschi C, et al. In a novel form of IFN-gamma receptor 1 deficiency, cell surface receptors fail to bind IFN-gamma. J Clin Invest 2000; 105(10): 1429-36.
  11. Doffinger R, Jouanguy E, Dupuis S, Fondaneche MC, Stephan JL, Emile JF, et al. Partial interferon-gamma receptor signaling chain deficiency in a patient with bacille Calmette-Guerin and Mycobacterium abscessus infection. J Infect Dis 2000; 181(1): 379-84.
  12. Rudko AA, Garaeva AF, Bragina EY, Babushkina NP, Kolokolova OV, Lipaenkova ON, et al. Mutations in genes underlying atypical familial mycobacteriosis are not found in tuberculosis patients from Siberian populations. Tuberculosis (Edinb) 2015; 95(2): 204-7.
  13. He J, Wang J, Lei D, Ding S. Analysis of functional SNP in ifng/ifngr1 in Chinese Han population with tuberculosis. Scand J Immunol 2010; 71(6): 452-8.
  14. Imai K, Okamoto T. Transcriptional repression of human immunodeficiency virus type 1 by AP-4. J Biol Chem 2006; 281(18): 12495-505.
  15. Haverkamp MH, van de Vosse E, van Dissel JT. Nontuberculous mycobacterial infections in children with inborn errors of the immune system. J Infect 2014; 68(Suppl 1): S134-S150.
  16. Sologuren I, Boisson-Dupuis S, Pestano J, Vincent QB, Fernandez-Perez L, Chapgier A, et al. Partial recessive IFN-gammaR1 deficiency: genetic, immunological and clinical features of 14 patients from 11 kindreds. Hum Mol Genet 2011; 20(8): 1509-23.
  17. Shahmohammadi S, Saffar M J, Rezai M S. BCG-osis after BCG vaccination in immunocompromised children: Case series and review. J Pediatr Rev 2014; 2(1): 62-74.
Journal of Isfahan Medical School
Volume 36, Issue 503 - Serial Number 503
September and October 2019
Pages 1349-1354

Files

History

  • Receive Date: 11 September 2018
  • Revise Date: 30 April 2024
  • Accept Date: 06 April 2022

Share

How to cite

Statistics