Necati Balamtekin, Gökhan BAYSOY, Nuray USLU KIZILKAN, Hulya DEMIR, İnci Nur SALTIK TEMİZEL, HASAN ÖZEN, Aysel YÜCE, Figen GÜRAKAN, ÇAĞMAN TAN, İlhan TEZCAN

The HLA groups and their relationship with clinical features in Turkish children and adolescents with celiac disease

Background. We aimed to investigate the relationship between human leukocyte antigens (HLA)-groups and clinical features, and degree of intestinal injury in children with celiac disease (CD). Methods. Study group included 73 (50 females, 68.5%) children with CD. Demographic and clinical features, accompanying autoimmune diseases, family history for CD and degree of damage in small intestinal mucosa (according to Marsh classification) at the time of diagnosis were determined. Twenty-two siblings of celiac patients without CD (15 females, 65.2%) consisted control group 1, and 66 (40 females, 60.6%) people from the normal population consisted control group 2. Results. The allele frequencies of HLA B8, B50, C6, C7, DR3, DR7, DQ2, and DR3 homozygosity were higher in the patient group. HLA DQ2 positivity was 89% in the patient group, 73.9 and 45.5% in control groups 1 and 2, respectively (p

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1. NIH Consensus Statement on Celiac Disease. NIH Consens State Sci Statements 2004; 21: 1-23.

2. Lebwohl B, Sanders DS, Green PHR. Coeliac disease. Lancet 2018; 391: 70-81.

3. Brown JRG, Singh P. Coeliac disease. Paediatr Int Child Health 2019; 39: 23-31.

4. Hill ID, Dirks MH, Liptak GS, et al; North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. Guideline for diagnosis and treatment of celiac disease in children: Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr 2005; 40: 1-19.

5. Revised criteria for diagnosis of coeliac disease. Report of Working Group of European Society of Paediatric Gastroenterology and Nutrition. Arch Dis Child 1990; 65: 909-911.

6. Ryan AW, Thornton JM, Brophy K, et al. Chromosome 5q candidate genes in coeliac disease: genetic variation at IL4, IL5, IL9, IL13, IL17B and NR3C1. Tissue Antigens 2005; 65: 150-155.

7. Bolognesi E, Karell K, Percopo S, et al. Additional factor in some HLA DR3/DQ2 haplotypes confers a fourfold increased genetic risk of celiac disease. Tissue Antigens 2003; 61: 308-316.

8. Louka AS, Sollid LM. HLA in coeliac disease: unravelling the complex genetics of a complex disorder. Tissue Antigens 2003; 61: 105-117.

9. Louka AS, Moodie SJ, Karell K, et al; European Genetics Cluster on Celiac Disease. A collaborative European search for non-DQA1*05-DQB1*02 celiac disease loci on HLA-DR3 haplotypes: analysis of transmission from homozygous parents. Hum Immunol 2003; 64: 350-358.

10. Tümer L, Altuntaş B, Hasanoglu A, Söylemezoglu O, Arinsoy T. Pattern of human leukocyte antigens in Turkish children with celiac disease. Pediatr Int 2000; 42: 678-681.

11. Tüysüz B, Dursun A, Kutlu T, et al. HLA-DQ alleles in patients with celiac disease in Turkey. Tissue Antigens 2001; 57: 540-542.

12. Erkan T, Kutlu T, Yılmaz E, Cullu F, Tümay T. Human leukocyte antigens in Turkish pediatric celiac patients. Turk J Pediatr 1999; 41: 181-188.

13. Kuloğlu Z, Doğancı T, Kansu A, et al. HLA types in Turkish children with celiac disease. Turk J Pediatr 2008; 50: 515-520.

14. Basturk A, Artan R, Yılmaz A. The incidence of HLADQ2/DQ8 in Turkish children with celiac disease and a comparison of the geographical distribution of HLA-DQ. Prz Gastroenterol 2017; 12: 256-261.

15. Megiorni F, Mora B, Bonamico M, 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.

16. Donat E, Planelles D, Capilla-Villanueva A, Montoro JA, Palau F, Ribes-Koninckx C. Allelic distribution and the effect of haplotype combination for HLA type II loci in the celiac disease population of the Valencian community (Spain). Tissue Antigens 2009; 73: 255-261.

17. Vogelsang H, Panzer S, Mayr WR, Granditsch G, Fischer GF. Distribution of HLA class I alleles differs in celiac disease patients according to age of onset. Dig Dis Sci 2003; 48: 611-614.

18. Ruiz del Prado MY, Olivares Lopez JL, Lazaro Almarza A, Lasierra Díaz MP. HLA system. Phenotypic and gene frequencies in celiac and healthy subjects from the same geographical area. Rev Esp Enferm Dig 2001; 93: 106-113.

19. Lopez-Vazquez A, Fuentes D, Rodrigo L, et al. MHC class I region plays a role in the development of diverse clinical forms of celiac disease in a Saharawi population. Am J Gastroenterol 2004; 99: 662-667.

20. Majorana A, Bardellini E, Ravelli A, Plebani A, Polimeni A, Campus G. Implications of gluten exposure period, CD clinical forms, and HLA typing in the association between celiac disease and dental enamel defects in children. A case-control study. Int J Paediatr Dent 2010; 20: 119-124.

21. Sumnik Z, Kolouskova S, Malcova H, et al. High prevalence of coeliac disease in siblings of children with type 1 diabetes. Eur J Pediatr 2005; 164: 9-12.

22. Britten AC, Mijovic CH, Barnett AH, Kelly MA. Differential expression of HLA-DQ alleles in peripheral blood mononuclear cells: alleles associated with susceptibility to and protection from autoimmune type 1 diabetes. Int J Immunogenet 2009; 36: 47-57.

23. Kahaly GJ, Frommer L, Schuppan D. Celiac disease and endocrine autoimmunity - the genetic link. Autoimmun Rev 2018; 17: 1169-1175.

24. Baker PR, Baschal EE, Fain PR, et al. Haplotype analysis discriminates genetic risk for DR3- associated endocrine autoimmunity and helps define extreme risk for Addison’s disease. J Clin Endocrinol Metab 2010; 95: E263-E270.

25. Mojibian M, Chakir H, Lefebvre DE, et al. Diabetesspecific HLA-DR-restricted proinflammatory T-cell response to wheat polypeptides in tissue transglutaminase antibody-negative patients with type 1 diabetes. Diabetes 2009; 58: 1789-1796.

26. Spurkland A, Sollid LM, Polanco I, Vartdal F, Thorsby E. HLA -DR and -DQ genotypes of celiac disease patients serologically typed to be non-DR3 or non-DR5/7. Hum Immunol 1992; 35: 188-192.

27. Freeman HJ. Risk factors in familial forms of celiac disease. World J Gastroenterol 2010; 16: 1828-1831.

28. 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: 319-324.

29. Jores RD, Frau F, Cucca F, et al. HLA-DQB1* 0201 homozygosis predisposes to severe intestinal damage in celiac disease. Scand J Gastroenterol 2007; 42: 48-53.

30. Karinen H, Kärkkäinen P, Pihlajamäki J, et al. HLA genotyping is useful in the evaluation of the risk for coeliac disease in the 1st-degree relatives of patients with coeliac disease. Scand J Gastroenterol 2006; 41: 1299-1304.

31. Al-Toma A, Goerres MS, Meijer JW, Peña AS, Crusius JB, Mulder CJ. Human leukocyte antigenDQ2 homozygosity and the development of refractory celiac disease and enteropathy-associated T-cell lymphoma. Clin Gastroenterol Hepatol 2006; 4: 315-319.

32. Simone R, Brizzolara R, Chiappori A, et al. A functional soluble form of CTLA-4 is present in the serum of celiac patients and correlates with mucosal injury. Int Immunol 2009; 21: 1037-1045.