Pediatric Gastroenterology, Hepatology & Nutrition

The Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition (대한소아소화기영양학회)
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Human Leukocyte Antigen-DQ Genotyping in Pediatric Celiac Disease

  • Stuti Pareek (Department of Pediatric Medicine, Sawai Man Singh Medical College) ;
  • Raj Kumar Gupta (Department of Pediatric Medicine, Sawai Man Singh Medical College) ;
  • Abhinav Sharma (Department of Pediatric Medicine, Sawai Man Singh Medical College) ;
  • Sandhya Gulati (Department of Pathology, Sawai Man Singh Medical College)
  • Received : 2022.04.07
  • Accepted : 2022.09.18
  • Published : 2023.01.15
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Abstract

Purpose: The purpose of this study was to determine the pattern of human leukocyte antigen (HLA)-DQ genotype in children diagnosed with celiac disease (CD) (biopsy proven), and to compare this with a control group; and secondarily, to correlate HLA genotypes with clinical profiles of CD. Methods: This cross-sectional comparative observational study included 26 controls and 52 patients diagnosed with CD who presented at Sir Padampat Mother and Child Health Institute, Jaipur, from May, 2017 to October, 2018. HLA DQ genotype was assessed for each patients and correlated with clinical profiles. Results: HLA DQ2/DQ8 genotypes were significantly more common in CD (present in 100.0% cases) than in controls (23.1%) in Northern India (Rajasthan). When HLA DQ2.5 and DQ8 were present together, individuals had significantly more atypical presentations and severe findings on duodenal biopsy. Similarly, patients with the HLA DQ 2.5 genotype were also predisposed to more severe endoscopic findings, while HLA DQ2.2 predisposed them to less severe biopsy findings. HLA DQ8 was significantly associated with later age at diagnosis (>5 years) and shorter stature. The highest HLA DQ relative risk (RR) for CD development was associated with HLA DQ2.5 and DQ2.2 in combination, followed by HLA DQ2.5 and DQ8 in combination, while HLA DQx.5 and HLA DQ2.2 together had the lowest risk. Conclusion: HLA DQ2/DQ8 genotypes are strongly associated with pediatric CD patients in northern India. These genotypes and their combinations may be associated with different clinical presentations of CD, and may help predict severity of CD.

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References

  1. Husby S, Koletzko S, Korponay-Szabo IR, Mearin ML, Phillips A, Shamir R, et al.; ESPGHAN Working Group on Coeliac Disease DiagnosisESPGHAN Gastroenterology CommitteeEuropean Society for Pediatric Gastroenterology, Hepatology, and Nutrition. European society for pediatric gastroenterology, hepatology, and nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr 2012;54:136-60. Erratum in: J Pediatr Gastroenterol Nutr 2012;54:572.
  2. Lionetti E, Catassi C. New clues in celiac disease epidemiology, pathogenesis, clinical manifestations, and treatment. Int Rev Immunol 2011;30:219-31. https://doi.org/10.3109/08830185.2011.602443
  3. Dieterich W, Ehnis T, Bauer M, Donner P, Volta U, Riecken EO, et al. Identification of tissue transglutaminase as the autoantigen of celiac disease. Nat Med 1997;3:797-801. https://doi.org/10.1038/nm0797-797
  4. Schuppan D, Junker Y, Barisani D. Celiac disease: from pathogenesis to novel therapies. Gastroenterology 2009;137:1912-33. https://doi.org/10.1053/j.gastro.2009.09.008
  5. Caillat-Zucman S. Molecular mechanisms of HLA association with autoimmune diseases. Tissue Antigens 2009;73:1-8. https://doi.org/10.1111/j.1399-0039.2008.01167.x
  6. Lindfors K, Koskinen O, Kaukinen K. An update on the diagnostics of celiac disease. Int Rev Immunol 2011;30:185-96. https://doi.org/10.3109/08830185.2011.595854
  7. Kuchay RA, Thapa BR, Mahmood A, Anwar M, Mahmood S. Lactase genetic polymorphisms and coeliac disease in children: a cohort study. Ann Hum Biol 2015;42:101-4. https://doi.org/10.3109/03014460.2014.944216
  8. Stankovic B, Radlovic N, Lekovic Z, Ristic D, Radlovic V, Nikcevic G, et al. HLA genotyping in pediatric celiac disease patients. Bosn J Basic Med Sci 2014;14:171-6. https://doi.org/10.17305/bjbms.2014.3.28
  9. Megiorni F, Mora B, Bonamico M, Barbato M, Montuori M, Viola F, et al. HLA-DQ and susceptibility to celiac disease: evidence for gender differences and parent-of-origin effects. Am J Gastroenterol 2008;103:997-1003. https://doi.org/10.1111/j.1572-0241.2007.01716.x
  10. Karell K, Louka AS, Moodie SJ, Ascher H, Clot F, Greco L, et al. HLA types in celiac disease patients not carrying the DQA1*05-DQB1*02 (DQ2) heterodimer: results from the European Genetics Cluster on Celiac Disease. Hum Immunol 2003;64:469-77. https://doi.org/10.1016/S0198-8859(03)00027-2
  11. Amarapurkar DN, Somani VS, Shah AS, Kankonkar SR. HLA - DQ genotyping in celiac disease in western India. Trop Gastroenterol 2015;36:174-8. https://doi.org/10.7869/tg.279
  12. Husby S, Koletzko S, Korponay-Szabo I, Kurppa K, Mearin ML, Ribes-Koninckx C, et al. European society paediatric gastroenterology, hepatology and nutrition guidelines for diagnosing coeliac disease 2020. J Pediatr Gastroenterol Nutr 2020;70:141-56. https://doi.org/10.1097/MPG.0000000000002497
  13. Rubio-Tapia A, Hill ID, Kelly CP, Calderwood AH, Murray JA; American College of Gastroenterology. ACG clinical guidelines: diagnosis and management of celiac disease. Am J Gastroenterol 2013;108:656-76; quiz 677. https://doi.org/10.1038/ajg.2013.79
  14. Srivastava A, Yachha SK, Mathias A, Parveen F, Poddar U, Agrawal S. Prevalence, human leukocyte antigen typing and strategy for screening among Asian first-degree relatives of children with celiac disease. J Gastroenterol Hepatol 2010;25:319-24. https://doi.org/10.1111/j.1440-1746.2009.06044.x
  15. Megiorni F, Pizzuti A. HLA-DQA1 and HLA-DQB1 in Celiac disease predisposition: practical implications of the HLA molecular typing. J Biomed Sci 2012;19:88.
  16. Murad H, Jazairi B, Khansaa I, Olabi D, Khouri L. HLA-DQ2 and -DQ8 genotype frequency in Syrian celiac disease children: HLA-DQ relative risks evaluation. BMC Gastroenterol 2018;18:70.
  17. Ramakrishna BS, Makharia GK, Chetri K, Dutta S, Mathur P, Ahuja V, et al. Prevalence of adult celiac disease in india: regional variations and associations. Am J Gastroenterol 2016;111:115-23. https://doi.org/10.1038/ajg.2015.398
  18. Kaur G, Sarkar N, Bhatnagar S, Kumar S, Rapthap CC, Bhan MK, et al. Pediatric celiac disease in India is associated with multiple DR3-DQ2 haplotypes. Hum Immunol 2002;63:677-82. https://doi.org/10.1016/S0198-8859(02)00413-5
  19. Rostami-Nejad M, Romanos J, Rostami K, Ganji A, Ehsani-Ardakani MJ, Bakhshipour AR, et al. Allele and haplotype frequencies for HLA-DQ in Iranian celiac disease patients. World J Gastroenterol 2014;20:6302-8. https://doi.org/10.3748/wjg.v20.i20.6302
  20. Khosravi A, Mansouri M, Rostami-Nejad M, Shahbazkhani B, Ekhlasi G, Kalantari E. The likelihood ratio and frequency of DQ2/DQ8 haplotypes in Iranian patients with celiac disease. Gastroenterol Hepatol Bed Bench 2016;9:18-24.
  21. Romanos J, Wijmenga C. Predicting susceptibility to celiac disease by genetic risk profiling. Ann Gastroenterol Hepatol 2010;1:11-8.
  22. Congia M, Cucca F, Frau F, Lampis R, Melis L, Clemente MG, et al. A gene dosage effect of the DQA1*0501/DQB1*0201DQA1*0501/DQB1*0201 allelic combination influences the clinical heterogeneity of celiac disease. Hum Immunol 1994;40:138-42.
  23. Zubillaga P, Vidales MC, Zubillaga I, Ormaechea V, Garcia-Urkia N, Vitoria JC. HLA-DQA1 and HLA-DQB1 genetic markers and clinical presentation in celiac disease. J Pediatr Gastroenterol Nutr 2002;34:548-54. https://doi.org/10.1097/00005176-200205000-00014