Abstract
Background:
Celiac disease (CD) has been associated with HLA class II heterodimers. This study aimed at determining the HLA genotypic and allelic distribution in Greek children with CD as compared with the general population.
Methods:
A total of 118 children with CD and 120 healthy individuals serving as controls were included in the study.
Results:
Higher frequencies for HLA-DQB1*02:01 (40.25 vs. 9.58%, P < 0.001) and DQB1*02:02 (20.34 vs. 5.42%, P < 0.001) were observed in patients with CD, whereas HLA-DQB1*03:01 (16.53 vs. 30.42%, P < 0.001), DQB1*05:01 (0.85 vs. 10%, P < 0.001), and DQB1*05:02 (5.51 vs. 17.92%, P < 0.001) were significantly lower, as compared with the controls. DQA1*02:01 (patients with CD vs. controls: 20.76 vs. 6.67%, P < 0.001) and DQA1*05:01 (40.25 vs. 9.58%, P < 0.001) were significantly more frequent in patients. The frequencies of HLA-DQA1* 01:01, *01:02, *01:04, and *05:05 were significantly lower in patients (P < 0.001). The haplotype mainly associated with CD was DRB1*03-DQB1*02:01-DQA1*05:01; patients with CD vs. controls: 39.83 vs. 9.58%, P < 0.001. In total, 84.75% of patients carried DQ2 (vs. 21.67% in controls, P < 0.001), whereas 11.02% were DQ8 positive/DQ2 negative.
Conclusion:
This study confirms the existing data and provides additional evidence supporting a strong genetic predisposition for CD associated with the class II alleles DQB1*02 and DQA1*05 encoding the serological specificity DQ2.
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References
Kagnoff MF . Overview and pathogenesis of celiac disease. Gastroenterology 2005;128:4 Suppl 1:S10–8.
Treem WR . Emerging concepts in celiac disease. Curr Opin Pediatr 2004;16:552–9.
Hill ID, Dirks MH, Liptak GS, et al. Guideline for the 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.
Madani S, Kamat D . Clinical guidelines for celiac disease in children: what does it mean to the pediatrician/family practitioner? Clin Pediatr (Phila) 2006;45:213–9.
Catassi C, Kryszak D, Louis-Jacques O, et al. Detection of Celiac disease in primary care: a multicenter case-finding study in North America. Am J Gastroenterol 2007;102:1454–60.
Tjon JM, van Bergen J, Koning F . Celiac disease: how complicated can it get? Immunogenetics 2010;62:641–51.
Ek J, Albrechtsen D, Solheim BG, Thorsby E . Strong association between the HLA-Dw3-related B cell alloantigen -DRw3 and coeliac disease. Scand J Gastroenterol 1978;13:229–33.
Keuning JJ, Peña AS, van Leeuwen A, van Hooff JP, va Rood JJ . HLA-DW3 associated with coeliac disease. Lancet 1976;1:506–8.
Mearin ML, Biemond I, Peña AS, et al. HLA-DR phenotypes in Spanish coeliac children: their contribution to the understanding of the genetics of the disease. Gut 1983;24:532–7.
Tosi R, Vismara D, Tanigaki N, et al. Evidence that celiac disease is primarily associated with a DC locus allelic specificity. Clin Immunol Immunopathol 1983;28:395–404.
Trabace S, Giunta A, Rosso M, et al. HLA-ABC and DR antigens in celiac disease. A study in a pediatric Italian population. Vox Sang 1984;46:102–6.
van Heel DA, Hunt K, Greco L, Wijmenga C . Genetics in coeliac disease. Best Pract Res Clin Gastroenterol 2005;19:323–39.
Louka AS, Sollid LM . HLA in coeliac disease: unravelling the complex genetics of a complex disorder. Tissue Antigens 2003;61:105–17.
Mazzarella G, Maglio M, Paparo F, et al. An immunodominant DQ8 restricted gliadin peptide activates small intestinal immune response in in vitro cultured mucosa from HLA-DQ8 positive but not HLA-DQ8 negative coeliac patients. Gut 2003;52:57–62.
Karell K, Louka AS, Moodie SJ, 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.
Hernández-Charro B, Donat E, Miner I, Aranburu E, Sánchez-Valverde F, Ramos-Arroyo MA . Modifying effect of HLA haplotypes located trans to DQB1*02-DRB1*03 in celiac patients of Southern Europe. Tissue Antigens 2008;71:213–8.
Bourgey M, Calcagno G, Tinto N, et al. HLA related genetic risk for coeliac disease. Gut 2007;56:1054–9.
Megiorni F, Mora B, Bonamico M, et al. HLA-DQ and risk gradient for celiac disease. Hum Immunol 2009;70:55–9.
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;73:255–61.
Husby S, Koletzko S, Korponay-Szabó IR, et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr 2012;54:136–60.
Margaritte-Jeannin P, Babron MC, Bourgey M, et al. HLA-DQ relative risks for coeliac disease in European populations: a study of the European Genetics Cluster on Coeliac Disease. Tissue Antigens 2004;63:562–7.
Kagnoff MF . Celiac disease: pathogenesis of a model immunogenetic disease. J Clin Invest 2007;117:41–9.
Congia M, Frau F, Lampis R, et al. A high frequency of the A30, B18, DR3, DRw52, DQw2 extended haplotype in Sardinian celiac disease patients: further evidence that disease susceptibility is conferred by DQ A1*0501, B1*0201. Tissue Antigens 1992;39:78–83.
Herrera M, Theiler G, Augustovski F, et al. Molecular characterization of HLA class II genes in celiac disease patients of Latin American Caucasian origin. Tissue Antigens 1994;43:83–7.
Michalski JP, McCombs CC, Arai T, et al. HLA-DR, DQ genotypes of celiac disease patients and healthy subjects from the West of Ireland. Tissue Antigens 1996;47:127–33.
Tighe MR, Hall MA, Ashkenazi A, Siegler E, Lanchbury JS, Ciclitira PJ . Celiac disease among Ashkenazi Jews from Israel. A study of the HLA class II alleles and their associations with disease susceptibility. Hum Immunol 1993;38:270–6.
Tighe MR, Hall MA, Barbado M, Cardi E, Welsh KI, Ciclitira PJ . HLA class II alleles associated with celiac disease susceptibility in a southern European population. Tissue Antigens 1992;40:90–7.
Green PH, Cellier C . Celiac disease. N Engl J Med 2007;357:1731–43.
Rostom A, Murray JA, Kagnoff MF . American Gastroenterological Association (AGA) Institute technical review on the diagnosis and management of celiac disease. Gastroenterology 2006;131:1981–2002.
Djilali-Saiah I, Schmitz J, Harfouch-Hammoud E, Mougenot JF, Bach JF, Caillat-Zucman S . CTLA-4 gene polymorphism is associated with predisposition to coeliac disease. Gut 1998;43:187–9.
Revised criteria for diagnosis of coeliac disease. Report of Working Group of European Society of Paediatric Gastroenterology and Nutrition. Arch Dis Child 1990;65:909–11.
Pedron B, Yakouben K, Adjaoud D, et al. Listing of common HLA alleles and haplotypes based on the study of 356 families residing in the Paris, France, area: implications for unrelated hematopoietic stem cell donor selection. Hum Immunol 2005;66:721–31.
Papassavas EC, Spyropoulou-Vlachou M, Papassavas AC, Schipper RF, Doxiadis IN, Stavropoulos-Giokas C . MHC class I and class II phenotype, gene, and haplotype frequencies in Greeks using molecular typing data. Hum Immunol 2000;61:615–23.
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Krini, M., Chouliaras, G., Kanariou, M. et al. HLA class II high-resolution genotyping in Greek children with celiac disease and impact on disease susceptibility. Pediatr Res 72, 625–630 (2012). https://doi.org/10.1038/pr.2012.133
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DOI: https://doi.org/10.1038/pr.2012.133
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