Human Leukocyte Antigen (HLA) DQ2 and DQ8 Haplotypes in Children with Celiac Disease
DOI:
https://doi.org/10.51253/pafmj.v75i1.10651Keywords:
Celiac disease, Gluten, Human leukocyte antigen (HLA).Abstract
Objective: To determine the frequency of human leukocyte antigen-DQ2 and -DQ8 haplotypes in children with celiac disease in a tertiary care hospital.
Study Design: Comparative cross-sectional study.
Place and Duration of Study: Paediatric Gastroenterology and Hepatology Departments Combined Military Hospital, Rawalpindi Pakistan, from Feb 2022 to Feb 2023.
Methodology: Diagnosed cases of celiac disease, from 1 to 15 years old, were selected as Cases (n=50), and an equal group of normal children of the same age as Control (n=50), were selected. Polymerase chain reaction for Human Leukocyte antigen (Human leukocyte antigen -DQ) genotyping was performed on all children.
Results: The most frequently observed haplotype was DQ2, followed by DQ8. Among celiac patients, 94% tested positive for human leukocyte antigen-DQ, with 82% DQ2, 10% DQ8, and 2% DQ2/DQ8 positive. 6% were negative for any HLA-DQ allele, while only 8% were DQ2 positive in the control group. The frequency of human leukocyte antigen -DQ between the two groups was statistically significant (p-value<0.05). The association between anti-tissue transglutaminase antibody levels and human leukocyte antigen -DQ was also statistically significant (p-value<0.05). Biopsy findings and gender had no statistically significant association with human leukocyte antigen -DQ (p-value>0.05).
Conclusion: Celiac disease has a varied spectrum of presentation, which often goes unrecognized by physicians. Therefore, genetic testing can be used as an additional diagnostic tool to reduce ambiguity and improve the accuracy of celiac disease diagnosis.
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Aziz DA, Kahlid M, Memon F, Sadiq K. Spectrum of celiac disease in paediatric population: Experience of tertiary care center from Pakistan. Pak J Med Sci 2017; 33(6): 1301-1306.
https://doi.org/10.12669/pjms.336.13489
Al-Toma A, Volta U, Auricchio R, Castillejo G, Sanders DS, Cellier C, et al. European Society for the Study of Coeliac Disease (ESsCD) guideline for coeliac disease and other gluten-related disorders. United European Gastroenterol J 2019; 7(5): 583-613. https://doi.org/10.1177/2050640619844125
Lodhi M, Saleem Z, Ayub A, Munir T, Hassan S. Epidemiology of celiac disease in the children presenting at the tertiary care hospital of Pakistan. Pak Armed Forces Med J 2022; 72(1): 299-302. https://doi.org/10.51253/pafmj.v72i1.8293
Javed F, Sattar F, Gill A, Lodhi Y, Iqbal K, Nazir A, et al. Clinical Spectrum of Celiac Disease in Children: Experience from A Public Hospital in Pakistan. Ann Punjab Med Coll 13(3): 192-196. https://doi.org/10.29054/apmc/2019.145
Sciurti M, Fornaroli F, Gaiani F, Bonaguri C, Leandro G, Di Mario F, et al. Genetic susceptibilty and celiac disease: what role do HLA haplotypes play? Acta Biomed 2018; 89(9-S): 17-21.
https://doi.org/10.23750/abm.v89i9-S.7953
Jamila, Kiani AR, Ahmed I, Yousafzai JK, Mehmood W, Khan SA, et al. Celiac disease in different age groups and gender in Pakistan. J Rawalpindi Med Coll 2018; 22(3): 244-247.
Siddiqui K, Uqaili AA, Rafiq M, Bhutto MA. Human leukocyte antigen (HLA)-DQ2 and -DQ8 haplotypes in celiac, celiac with type 1 diabetic, and celiac suspected pediatric cases. Medicine 2021; 100(11): e24954.
https://doi.org/10.1097/MD.0000000000024954
Aboulaghras S, Piancatelli D, Oumhani K, Balahbib A, Bouyahya A, Taghzouti K, et al. Pathophysiology and immunogenetics of celiac disease. Clin Chim Acta 2022; 528: 74-83. https://doi.org/10.1016/j.cca.2022.01.022
Catassi C, Verdu EF, Bai JC, Lionetti E. Coeliac disease. Lancet 2022; 399(10344): 2413-2426.
https://doi.org/10.1016/S0140-6736(22)00794-2
Lindfors K, Ciacci C, Kurppa K, Lundin KEA, Makharia GK, Mearin ML, et al. Coeliac disease. Nat Rev Dis Primers 2019; 5(1): 3. https://doi.org/10.1038/s41572-018-0054-z
Saleem N, Ali S, Ahmed TA, Iqbal M, Bashir M. HLA-DR alleles among Pakistani patients of coeliac disease. J Pak Med Assoc. 2013; 63(10): 1271-1274.
Poddighe D, Capittini C. The role of HLA in the association between IgA deficiency and celiac Disease. Dis Markers 2021; 2021: 8632861.
https://doi.org/10.1155/2021/8632861
Alam M, Tipu HN, Ahmad D, Hussain M, Khalid UB, Ijaz N, et al. HLA-DQ2 and HLA-DQ8 Alleles in celiac disease patients and healthy controls. J Coll Physicians Surg Pak 2022; 32(2): 157-160. https://doi.org/10.29271/jcpsp.2022.02.157
Krini M, Chouliaras G, Kanariou M, Varela I, Spanou K, Panayiotou J, et al. HLA class II high-resolution genotyping in Greek children with celiac disease and impact on disease susceptibility. Pediatr Res 2012; 625–630.
https://doi.org/10.1038/pr.2012.133
Stanković B, Radlović N, Leković Z, Ristić D, Radlović V, Nikčević G, et al. HLA genotyping in pediatric celiac disease patients. Bosn J Basic Med Sci 2014; 14(3): 171-6.
https://doi.org/10.17305/bjbms.2014.3.28
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(20): 6302-6308.
https://doi.org/10.3748/wjg.v20.i20.6302
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(1): 88.
https://doi.org/10.1186/1423-0127-19-88
Pareek S, Gupta RK, Sharma A, Gulati S. Human leukocyte antigen-DQ genotyping in pediatric celiac disease. Pediatr Gastroenterol Hepatol Nutr 2023; 26(1): 50-57.
https://doi.org/10.5223/pghn.2023.26.1.50
Sahin Y, Mermer S. Frequency of celiac disease and distribution of HLA-DQ2/DQ8 haplotypes among siblings of children with celiac disease. World J Clin Pediatr 2022; 11(4): 351-359.
https://doi.org/10.5409/wjcp. v11.i4.351
Selleski n, Almeida IM, Almeida FC de, Pratesi CB, Nóbrega YK de M, Gandolfi I, et al. prevalence of celiac disease predisposing genotypes, including hla-dq2.2 variant, in Brazilian children. Arq Gastroenterol 2018; 55(1): 82–85.
https://doi.org/10.1590/s0004-2803.201800000-16
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. https://doi.org/10.1186/s12876-018-0802-2
Jafari SA, Chaichi Z, Hammoud M, Kianifar H, Mir F. HLADQ2 and HLADQ8 alleles are associated with celiac disease in children. Int J Pediatr 2022; 10(8): 16498-16504.
https://doi.org/10.22038/ijp.2022.64904.4908
Tian S, Weidong L, Ting L, Huan L, Wenjia H, Qiang L, et al. HLA-DQ genotype distribution and risk evaluation of celiac disease in Northwest China. Scand J Gastroenterol 2023; 58: 5, 471-476.
https://doi.org/10.1080/00365521.2022.2147801
Salarian L, Khavaran M, Dehghani SM, Mashhadiagha A, Moosavi SA, Rezaeianzadeh S, et al. Extra-intestinal manifestations of Celiac disease in children: their prevalence and association with human leukocyte antigens and pathological and laboratory evaluations. BMC Pediatr 2023; 23(1): 8.
https://doi.org/10.1186/s12887-022-03826-w
Castillejo G, Ochoa-Sangrador C, Pérez-Solís D, Cilleruelo ML, Donat E, García-Burriel JI, et al. Coeliac Disease Case–Control Study: Has the time come to explore beyond patients at risk? Nutrients 2023; 15(5): 1267.
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Copyright (c) 2025 Ifnan Shamraiz, Shaista Naz, Saba Idrees, Farooq Ikram, Husna Khan, Samina Khan
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