COMBINED IMPACT OF STREPTOCOCCUS PYOGENES INFECTION, ANTI-STREPTOLYSIN O RESPONSE, AND IL-10/TNF-Α GENE POLYMORPHISMS ON SUSCEPTIBILITY TO RECURRENT TONSILLITIS



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Objective: The aim of the study was to examine bacteriological profile of recurrent tonsillitis, and assess the association between Streptococcus pyogenes infection, anti-streptolysin O (ASO) levels, and cytokine gene polymorphisms (IL-10 and TNF-a).Methods: This study involved 100 participants, i.e., 50 patients with recurrent tonsillitis and 50 healthy controls. Bacteriological culture and identification were done on throat swab samples. Serum ASO was determined serologically by standard procedures. Genotype of IL -10 ( -1082 G/A) and TNF- ( -308 G/A) was done by molecular methods. These were statistically analyzed to compare the groups and evaluate correlations between the variables. Results: Bacteriological tests showed that 76% of the patient samples were culture-positive, and Streptococcus pyogenes was the most common isolate (63.2%). The level of ASO was markedly elevated in the patient group as compared to the control group with mean levels of 356.8 ± 120.5 IU/mL and 112.4 ± 48.7 IU/mL respectively (p < 0.05).Genetic analysis showed that there was increased prevalence of IL-10 AA genotype (low producer) and TNF- alpha AA genotype (high producer) in patients. Strong correlation between TNF-alpha polymorphism and disease susceptibility was found whereby there was an increased prevalence of the A allele of TNF-a in the patients. Correlation analysis revealed that TNF-alpha polymorphism was positively associated with ASO levels (r = +0.46) and IL-10 polymorphism was negatively associated with ASO levels (r = -0.39) and both these were statistically significant (p < 0.05).Conclusion: Recurrent tonsillitis is clearly linked to persistent infection with Streptococcus pyogenes, high levels of anti-streptolysin O (ASO) as well as to polymorphisms of the genes coding for cytokines. The results indicate that, the allelic variation in immune-response genes might be associated with susceptibility to recurrent tonsillitis and the immune response to streptococcal infection, because these are more common in patients. These results point to the need to consider bacteriological, immunological and genetic parameters in explaining the mechanisms of recurrent tonsillitis and could help to develop novel diagnostic and therapeutic strategies.

About the authors

Rana Talib Mohsen

University of Anbar, Iraq

Author for correspondence.
Email: Ranamohsen2011@gmail.com

assistant professor

Iraq

References

  1. Abbas AK, Lichtman AH, Pillai S. Cellular and Molecular Immunology. 10th ed. Elsevier; 2021.
  2. Abdulameer KA, Hashim Z. Genetic polymorphism in TNF-α promoter region: its association with severity and susceptibility to rheumatoid arthritis in Iraqi patients with active disease. Iraqi J Pharm Sci. 2023;32(2):46-57. doi: 10.31351/vol32iss2pp46-57.
  3. Aggarwal BB. Signalling pathways of the TNF superfamily: a double-edged sword. Nat Rev Immunol. 2003;3(9):745-756. doi: 10.1038/nri1184.
  4. Ahmad AA, Barani SS, Sultan SJ. Role of the IL-10 gene and its genetic variations in the development of diabetes mellitus in women. World Acad Sci J. 2025;7:104. doi: 10.3892/wasj.2025.392.
  5. Al-Charrakh AH, Al-Khafaji JK, Al-Rubaye RH. Prevalence of β-hemolytic groups C and F streptococci in patients with acute pharyngitis. N Am J Med Sci. 2011;3(3):129-136. doi: 10.4297/najms.2011.3129.
  6. Al-Meghaiseeb ES, Al-Robayan AA, Al-Otaibi MM, Arfin M, Al-Asmari AK. Association of tumor necrosis factor-α and -β gene polymorphisms in inflammatory bowel disease. J Inflamm Res. 2016;9:133-140. doi: 10.2147/JIR.S101225.
  7. Alrayah M. The prevalence and management of chronic tonsillitis: experience from secondary care hospitals in Rabak City, Sudan. Cureus. 2023;15(2):e34914. doi: 10.7759/cureus.34914.
  8. Brandtzaeg P. Immune functions of nasopharyngeal lymphoid tissue. Adv Otorhinolaryngol. 2011;72:20-24.. doi: 10.1159/000324588
  9. Carapetis JR, Steer AC, Mulholland EK, Weber M. The global burden of group A streptococcal diseases. Lancet Infect Dis. 2005;5(11):685-694. doi: 10.1016/S1473-3099(05)70267-X.
  10. Chiche JD, Siami S, Dhainaut JF, Mira JP. Cytokine polymorphisms and susceptibility to severe infectious diseases. Sepsis. 2001;4(3):209-215. doi: 10.1023/A:1013222407924.
  11. Cohen R, de La Rocque F, Lécuyer A, Wollner C, Bodin MJ, Wollner A. Study of the acceptability of antibiotic syrups, suspensions, and oral solutions prescribed to pediatric outpatients. Eur J Pediatr. 2009;168(7):851-857. doi: 10.1007/s00431-008-0857-0.
  12. Couper KN, Blount DG, Riley EM. IL-10: the master regulator of immunity to infection. J Immunol. 2008;180(9):5771-5777. doi: 10.4049/jimmunol.180.9.5771.
  13. Cunningham MW. Pathogenesis of group A streptococcal infections. Clin Microbiol Rev. 2000;13(3):470-511.. doi: 10.1128/CMR.13.3.470
  14. da Silva Graça Amoras E, de Morais TG, do Nascimento Ferreira R, Gomes STM, de Sousa FDM, de Paula Souza I, et al. Association of cytokine gene polymorphisms and their impact on active and latent tuberculosis in Brazil's Amazon region. Biomolecules. 2023;13(10):1541. doi: 10.3390/biom13101541.
  15. Danchin MH, Carlin JB, Devenish W, Nolan TM, Carapetis JR. New normal ranges of antistreptolysin O and antideoxyribonuclease B titres for Australian children. J Paediatr Child Health. 2005;41(11):583-586. doi: 10.1111/j.1440-1754.2005.00726.x.
  16. Dekker JP. Within-host evolution of bacterial pathogens in acute and chronic infection. Annu Rev Pathol. 2024;19:203-226. doi: 10.1146/annurev-pathmechdis-051122-111408.
  17. Delice S, Adaleti R, Cevan S, Alagoz P, Bedel A, Nuhoglu C, et al. Detection of upper limit of normal values of anti-DNase B antibody in children's age groups who were admitted to hospital with noninfectious reasons. North Clin Istanb. 2015;2(2):136-141. doi: 10.14744/nci.2015.39358.
  18. Hassan S, Mohsen RT, Farman MS. Interleukin-37 gene single nucleotide polymorphisms and patient susceptibility to hepatitis B and C infection. Opera Medica et Physiologica. 2024;11(1):52-60. doi: 10.24412/2500-2295-2024-1-52-60.
  19. Hussein MU, Mohsen RT. Evaluation of a plasma torch in the inhibition of Escherichia coli bacteria in water. AIP Conf Proc. 2024;3051:020014. doi: 10.1063/5.0191668.
  20. Ibekwe TS, Nwaorgu OG. Classification and management challenges of otitis media in a resource-poor country. Niger J Clin Pract. 2011;14(3):262-269. doi: 10.4103/1119-3077.86764.
  21. Iman AK, Mohsen RT, Alalwani AK. Association of microRNA-155 gene polymorphism and the incidence of systemic lupus erythematosus in Iraqi patients. Asia Pac J Mol Biol Biotechnol. 2023;31(4):66-100. doi: 10.35118/apjmbb.2023.031.4.10.
  22. Kaplan EL, Rothermel CD, Johnson DR. Antistreptolysin O and anti-deoxyribonuclease B titers: normal values for children ages 2 to 12 in the United States. Pediatrics. 1998;101(1 Pt 1):86-88. doi: 10.1542/peds.101.1.86.
  23. Khademi SMH, Sazinas P, Jelsbak L. Within-host adaptation mediated by intergenic evolution in Pseudomonas aeruginosa. Genome Biol Evol. 2019;11(5):1385-1397. doi: 10.1093/gbe/evz083.
  24. Khan AW, Farooq M, Hwang MJ, Haseeb M, Choi S. Role of interleukins in immune-mediated diseases. Int J Mol Sci. 2023;24(9):7960. doi: 10.3390/ijms24097960.
  25. Kline KA, Bowdish DM. Infection in an aging population. Curr Opin Microbiol. 2016;29:63-67. doi: 10.1016/j.mib.2015.11.003.
  26. Medzhitov R. Origin and physiological roles of inflammation. Nature. 2008;454(7203):428-435.. doi: 10.1038/nature07201
  27. Mohsen RT, Al-Taee HZ, Wafaa HH, Anmar K. Iraqi patients with a single-nucleotide polymorphism of interleukin-10 -1082G/A and interleukin-6 -174G/C susceptibility to asthma. Asia Pac J Mol Biol Biotechnol. 2024;32(3):49-55 . doi: 10.35118/apjmbb.2024.032.3.06.
  28. Mohsen RT, Wafaa HH, Thaer AH, Al-Taee HZ. Association between asthma and the tumor necrosis factor alpha-308 gene polymorphism in Iraqi patient. Asia Pac J Mol Biol Biotechnol. 2025;33(1):69-76. doi: 10.35118/apjmbb.2025.033.1.08.
  29. Moore KW, de Waal Malefyt R, Coffman RL, O'Garra A. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol. 2001;19:683-765. doi: 10.1146/annurev.immunol.19.1.683.
  30. Mosser DM, Zhang X. Interleukin-10: new perspectives on an old cytokine. Immunol Rev. 2008;226:205-218. doi: 10.1111/j.1600-065X.2008.00706.x.
  31. Mwita JC, Sajini S, Engel K, Machiya TB, Engel ME. Prevalence of Group A Streptococcal pharyngitis and antibiotic susceptibility in paediatric patients with sore throats in Gaborone, Botswana. Trop Med Int Health. 2026;31(2):176-180. doi: 10.1111/tmi.70055.
  32. Nizet V. Understanding how leading bacterial pathogens subvert innate immunity to reveal novel therapeutic targets. J Allergy Clin Immunol. 2007;120(1):13-22. doi: 10.1016/j.jaci.2007.06.005.
  33. O'Garra A, Vieira P. Regulatory T cells and mechanisms of immune system control. Nat Med. 2004;10(8):801-805. doi: 10.1038/nm0804-801.
  34. Park JS, Gamboni-Robertson F, He Q, Svetkauskaite D, Kim JY, Strassheim D, et al. High mobility group box 1 protein interacts with multiple Toll-like receptors. Am J Physiol Cell Physiol. 2006;290(3):C917-C924. doi: 10.1152/ajpcell.00401.2005.
  35. Salman HF, Mohsen R, Alalwani AK. Single-nucleotide polymorphism in Iraqi patients of TNF-α-308G/A (rs1800629) susceptibility to asthma. Jordan Medical Journal. 2026;60(1). doi: 10.35516/jmj.v60i1.3601.
  36. Saraiva M, O'Garra A. The regulation of IL-10 production by immune cells. Nat Rev Immunol. 2010;10(3):170-181. doi: 10.1038/nri2711.
  37. Shafikhani S. Closing editorial: immunopathogenesis of bacterial infection. Cells. 2025;14(23):1894.. doi: 10.3390/cells14231894
  38. Shulman ST, Bisno AL, Clegg HW, Gerber MA, Kaplan EL, Lee G, et al. Clinical practice guideline for the diagnosis and management of group A streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of America. Clin Infect Dis. 2012;55(10):1279-1282. doi: 10.1093/cid/cis847.
  39. Steer AC, Vidmar S, Ritika R, Kado J, Batzloff M, Jenney AW, et al. Normal ranges of streptococcal antibody titers are similar whether streptococci are endemic to the setting or not. Clin Vaccine Immunol. 2009;16(2):172-175. doi: 10.1128/CVI.00291-08.
  40. Thacharodi A, Hassan S, Vithlani A, Ahmed T, Kavish S, Geli Blacknell NM, et al. The burden of group A Streptococcus (GAS) infections: the challenge continues in the twenty-first century. iScience. 2025;28(1):111677. doi: 10.1016/j.isci.2024.111677.
  41. Tirago TD, Worku M, Nima TM, Ormago MD. Microbial composition, antibiotic sensitivity patterns, and contributing factors among children with tonsillitis in Hawassa Town, Sidama, Ethiopia. Int J Microbiol. 2025;2025:6366378.. doi: 10.1155/ijm/6366378
  42. Turner DM, Williams DM, Sankaran D, Lazarus M, Sinnott PJ, Hutchinson IV. An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet. 1997;24(1):1-8. doi: 10.1111/j.1365-2370.1997.tb00001.x.
  43. Turner MD, Nedjai B, Hurst T, Pennington DJ. Cytokines and chemokines: at the crossroads of cell signalling and inflammatory disease. Biochim Biophys Acta. 2014;1843(11):2563-2582. doi: 10.1016/j.bbamcr.2014.05.014.
  44. Walker MJ, Barnett TC, McArthur JD, Cole JN, Gillen CM, Henningham A, et al. Disease manifestations and pathogenic mechanisms of Group A Streptococcus. Clin Microbiol Rev. 2014;27(2):264-301. doi: 10.1128/CMR.00101-13.
  45. Wannamaker LW. Differences between streptococcal infections of the throat and of the skin. N Engl J Med. 1970;282(2):78-85. doi: 10.1056/NEJM197001082820206.
  46. Wilson AG, Symons JA, McDowell TL, McDevitt HO, Duff GW. Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation. Proc Natl Acad Sci U S A. 1997;94(7):3195-3199. doi: 10.1073/pnas.94.7.3195.
  47. Windfuhr JP, Toepfner N, Steffen G, Waldfahrer F, Berner R. Clinical practice guideline: tonsillitis I. Diagnostics and nonsurgical management. Eur Arch Otorhinolaryngol. 2016;273(4):973-987. doi: 10.1007/s00405-015-3872-6.
  48. Xia Z, Wang Y, Liu F, Shu H, Huang P. Association between TNF-α-308, +489, −238 polymorphism and COPD susceptibility: an updated meta-analysis and trial sequential analysis. Front Genet. 2022;12:772032. doi: 10.3389/fgene.2021.772032.

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