Document Type : original article
1 Department of Pediatric Gastroenterology, Ghaem Medical Center, Mashhad University of medical sciences, Mashhad, Iran.
2 Department of Pediatric, Faculity of Medicine, Mashhad University of Medical Siences, Mashhad, Iran
3 Department of Pediatrics, Mashhad University of Medical Sciences, Mashhad, Iran..
4 Department of Gastroenterology,Faculty of medicine,Mashhad university of medical sciences,Mashhad,Iran
5 Department of Pediatrics, Mashhad University of Medical Sciences, Mashhad, Iran.
Background: Celiac disease is the permanent intolerance to dietary gluten, the major protein component of wheat. The role of human leukocyte antigen (HLA) DQ2 heterodimer (DQA1*0501-DQB1*0201) in presenting gluten peptides to effectors T cells in celiac disease (CD) has been well documented. Epidemiological studies of the disease in Iran are not available. This study was aimed to investigate the frequency of HLADQ2 and HLADQ8 in children with celiac disease in Mashhad city.
Methods: This case-control study was conducted on 25 celiac patients and 25 matched healthy controls for HLA typing of DQ2/DQ8. CD diagnosis was reached in 25 subjects, according to the revised criteria of the European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) and North American Society for Pediatric Gastroenterology, Hepatology and Nutrition criteria (NASPGHAN). Sensitivity, specificity, and negative and positive predictive values were calculated.
Results: Mean age was 134.06±30.48 months in case and control groups, with no statistical difference between the two groups. 48% of cases and controls were male, and 52 % were female. HLA-DQ2/8 was positive with 80% (CI 95%:64-95), sensitivity was 80% (CI 95%:58-92), specificity 48% (CI 95%:28-68), NPV 70.58% (CI 95%:44-88), PPV 61(CI 95%:42.2-76.5) and accuracy was 64%.
Conclusion: A positive association was found between HLA DQ2/8 and Iranian celiac disease. As negative and predictive values were high, HLA typing may be considered a beneficial test for diagnosis confirmation.
- Rostami-Nejad M, Villanacci V, Hogg-Kollars S, et al. Endoscopic and histological pitfalls in the diagnosis of celiac disease: A multicentre study assessing the current practice. Rev Esp Enferm Dig. 2013; 105(6):326-333.
- Anderson RP, Henry MJ, Taylor R, et al. A novel serogenetic approach determines the community prevalence of celiac disease and informs improved diagnostic pathways. BMC medicine. 2013; 11(1):1-13.
- Amirzargar A, Mytilineos J, Farjadian S, Doroudchi M, Scherer S, Opelz G, Ghaderi A. Human leukocyte antigen class II allele frequencies and haplotype association in Iranian normal population. Hum Immunol. 2001; 62:1234–1238. [PubMed] [Google Scholar]
- Farjadian S, Naruse T, Kawata H, Ghaderi A, Bahram S, Inoko H. Molecular analysis of HLA allele frequencies and haplotypes in Baloch of Iran compared with related populations of Pakistan. Tissue Antigens. 2004; 64:581–587. [PubMed] [Google Scholar]
- Farjadian S, Moqadam FA, Ghaderi A. HLA class II gene polymorphism in Parsees and Zoroastrians of Iran. Int J Immunogenet. 2006; 33:185–191. [PubMed] [Google Scholar]
- Farjadian S, Ghaderi A. HLA class II similarities in Iranian Kurds and Azeris. Int J Immunogenet. 2007; 34:457–463. [PubMed] [Google Scholar]
- Monsuur AJ, de Bakker PI, Zhernakova A, Pinto D, Verduijn W, Romanos J, Auricchio R, Lopez A, van Heel DA, Crusius JB, et al. Effective detection of human leukocyte antigen risk alleles in celiac disease using tag single nucleotide polymorphisms. PLoS One. 2008; 3:e2270. [PMC free article] [PubMed] [Google Scholar]
- Rostami-Nejad M, Romanos J, Rostami R, 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; 20:6302–308.
- Greco L, Corazza G, Babron M-C, et al. Genome search in celiac disease. The American Journal of Human Genetics. 1998; 62(3):669-675.
- Martina S, Fabiola F, Federica G, et al. Genetic susceptibility and celiac disease: what role do HLA haplotypes play? Acta Bio Medica: Atenei Parmensis. 2018; 89(Suppl 9):17.
- Brown NK, Guandalini S, Semrad C, Kupfer SS. A clinician's guide to celiac disease HLA genetics. Official journal of the American College of Gastroenterology| ACG. 2019; 114(10):1587-1592.
- Megiorni F, Pizzuti A. HLA-DQA1 and HLA-DQB1 in Celiac disease predisposition: practical implications of the HLA molecular typing. Journal of biomedical science. 2012; 19(1):1-5.
- Ramakrishna B, Makharia GK, Chetri K, et al. Prevalence of adult celiac disease in India: regional variations and associations. Official journal of the American College of Gastroenterology| ACG. 2016; 111(1):115-123.
- Di Sabatino A, Vanoli A, Giuffrida P, Luinetti O, Solcia E, Corazza GR. The function of tissue transglutaminase in celiac disease. Autoimmunity reviews. 2012; 11(10):746-753.
- Troncone R, Discepolo V. Celiac disease and autoimmunity. Journal of pediatric gastroenterology and nutrition. 2014; 59:S9-S11.
- Guandalini S, Discepolo V. Celiac disease. Textbook of pediatric gastroenterology, hepatology and nutrition. 2022:525-548.
- Dolinšek J, Urlep D, Karell K, Partanen J, Mičetić-Turk D. The prevalence of celiac disease among family members of celiac disease patients. Wiener klinische Wochenschrift. 2004; 116.
- Mishra A, Prakash S, Kaur G, et al. Prevalence of celiac disease among first-degree relatives of Indian celiac disease patients. Digestive and Liver Disease. 2016; 48(3):255-259.
- Neuhausen SL, Steele L, Ryan S, et al. Co-occurrence of celiac disease and other autoimmune diseases in celiacs and their first-degree relatives. Journal of autoimmunity. 2008; 31(2):160-165.
- Romanos J, Van Diemen CC, Nolte IM, et al. Analysis of HLA and non-HLA alleles can identify individuals at high risk for celiac disease. Gastroenterology. 2009; 137(3):834-840. e833.
- Pietzak MM, Schofield TC, McGinniss MJ, Nakamura RM. Stratifying risk for celiac disease in a large at-risk United States population by using HLA alleles. Clinical Gastroenterology and Hepatology. 2009; 7(9):966-971.
- Mohammadibakhsh R, Sohrabi R, Salemi M, Mirghaed MT, Behzadifar M. Celiac disease in Iran: a systematic review and meta-analysis. Electronic physician. 2017; 9(3):3883.
- Murad H, Jazairi B, Khansaa I, Olabi D, Khouri L. HLA-DQ2 and-DQ8 genotype frequency in Syrian celiac disease children: HLA-DQ relative risk evaluation. BMC gastroenterology. 2018; 18(1):1-4.
- Basturk A, Artan R, Yilmaz A. The incidence of HLA-DQ2/DQ8 in Turkish children with celiac disease and a comparison of the geographical distribution of HLA-DQ. Przeglad Gastroenterologiczny. 2017; 12(4):256.
- Polvi A, Arranz E, Fernandez-Arquero M, et al. HLA-DQ2-negative celiac disease in Finland and Spain. Human immunology. 1998; 59(3):169-175.
- Rostami-Nejad M, Romanos J, Rostami K, et al. Allele and haplotype frequencies for HLA-DQ in Iranian celiac disease patients. World journal of gastroenterology: WJG. 2014; 20(20):6302.
- Alarida K, Harown J, Di Pierro MR, Drago S, Catassi C. HLA-DQ2 and-DQ8 genotypes in celiac and healthy Libyan children. Digestive and Liver Disease. 2010; 42(6):425-427.
- Özgenel ŞM, Temel T, Teke HÜ, Yıldız P, Korkmaz H, Özakyol A. HLA-DQ2/DQ8 frequency in adult patients with celiac disease, their first-degree relatives, and normal population in Turkey. The Turkish Journal of Gastroenterology. 2019 Apr; 30(4):321.
- Piccini B, Vascotto M, Serracca L, et al. HLA-DQ typing in the diagnostic algorithm of celiac disease. Revista Espanola de enfermedades digestivas. 2012; 104(5):248.
- Alarida K, Harown J, Di Pierro MR, Drago S, Catassi C. HLA-DQ2 and -DQ8 genotypes in celiac and healthy Libyan children. Digestive and Liver Disease. 2010/06/01/ 2010; 42(6):425-427.
- 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. Human immunology. 2003; 64(4):469-477.
- Delgado JF, Amengual MJ, Veraguas A, Rodríguez E, de Los Santos MM, Guallarte MP. Paediatric celiac patients carrying the HLA‐DR 7‐DQ 2 and HLA‐DR 3‐DQ 2 haplotypes display small clinical differences. Acta Paediatrica. 2014; 103(6):e238-e242.
- Šumník Z, Koloušková S, Cinek O, Kotalova R, Vavřinec J, Snajderova M. HLA‐DQA1* 05‐DQB 1* 0201 positivity predisposes to coeliac disease in Czech diabetic children. Acta Paediatrica. 2000; 89(12):1426-1430.
- Pallav K, Kabbani T, Tariq S, Vanga R, Kelly CP, Leffler DA. Clinical utility of celiac disease-associated HLA testing. Dig Dis Sci. 2014; 59(9):2199-2206.
- Kurppa K, Salminiemi J, Ukkola A, et al. Utility of the new ESPGHAN criteria for the diagnosis of celiac disease in at-risk groups. Journal of pediatric gastroenterology and nutrition. Mar 2012; 54(3):387-391.
- Hadithi M, von Blomberg BME, Crusius JBA, et al. Accuracy of serologic tests and HLA-DQ typing for diagnosing celiac disease. Annals of internal medicine. 2007; 147(5):294-302.
- Sahin Y. Clinical evaluation of children with celiac disease: A single-center experience. Archives of Clinical Gastroenterology. 2020; 6(1):026-030.
- Catassi C, Fasano A. Celiac disease as a cause of growth retardation in childhood. Current opinion in pediatrics. 2004; 16(4):445-449.
- Sahin Y. Celiac disease in children: A review of the literature. World J Clin Pediatr. 2021; 10(4):53-71.
- Rodrigo-Sáez L, Fuentes-Álvarez D, Pérez-Martínez I, et al. Differences between pediatric and adult celiac disease. Revista espanola de enfermedades digestivas. 2011; 103(5):238.