Association of tissue transglutaminase IgA antibodies with HLA DQ2/DQ8 haplotypes in clinically suspected cases of celiac disease in Pakistani population

Authors

  • Sara Waqar Khan Armed Forces Institute of Pathology (National University of Medical Sciences), Rawalpindi Pakistan
  • Sana Nawaz Armed Forces Institute of Pathology (National University of Medical Sciences), Rawalpindi Pakistan
  • Muhammad Aftab Hassan Armed Forces Institute of Pathology (National University of Medical Sciences), Rawalpindi Pakistan

DOI:

https://doi.org/10.55629/pakjpathol.v37i1.908

Abstract

Objective: To determine the presence of anti TTG IgA in clinically suspected Celiac disease (CD) patients and associate their results with HLA-DQ 2/ DQ 8 haplotypes.

Material and Methods: This analytical cross-sectional study was conducted at Department of Immunology, Armed Forces Institute of Pathology, NUMS, Rawalpindi, from September 2024 to February 2025. A total of 277 clinically suspected Celiac disease  cases were tested for anti-TTG IgA antibodies by ELISA technique and HLA-DQ 2/ DQ 8 haplotypes by sequence specific PCR. Associations were analyzed using chi-square tests and logistic regression.

Results: Out of 277 suspected celiac disease patients, 53 (19.1%) were anti-TTG IgA positive; among them, 43 (81%) had HLA-DQ2/DQ8. HLA-DQ2.5 was the most common genotype (48%), while overall HLA-DQ2 (and subtypes) was present in 59.6% and HLA-DQ8 in 2.16%. Anti-TTG IgA showed a significant association with HLA-DQ2/DQ8 (p=0.001). HLA-DQ2.5 was a significant predictor (OR=3.98, 95% CI: 1.88–8.44; p<0.001), whereas HLA-DQ2.2 and HLA-DQ8 were not significant.

Conclusion: HLA-DQ 2.5 is a strong genetic marker for celiac disease  in Pakistan, significantly associated with anti-TTG IgA positivity. The limited predictive value of HLA-DQ 8 and HLA-DQ 2.2 highlights the need for population-specific diagnostic strategies. Combining serological and genetic testing enhances diagnostic accuracy, enabling early detection and improved disease management.

Keywords: Anti-TTG IgA, Celiac disease, HLA-DQ 2, HLA-DQ 8

References

Alaa Jawad Kadhum. Evaluation of HLA-DQ2 and DQ8 haplotypes in patients with celiac disease correlation with circulating anti-tissue transglutaminase and anti-gliadin antibodies. Biology. 2021. DOI: https://doi.org/10.51699/ajbns .v2i2.603

Clouzeau‐Girard H, Rebouissoux L, Taupin J, Le Bail B, Kalach N, Michaud L, et al. HLA‐DQ Genotyping combined with serological markers for the diagnosis of celiac disease: Is intestinal biopsy still mandatory? J Pediatr Gastroenterol Nutr. 2011; 52(6): 729–33. DOI: https://doi.org /10.1097 /MPG.0b013e31820a724d

Sghiri R, Hassine H Ben, Almogren A, Shakoor Z, Alswayyed M. Diagnostic performances of celiac disease serological tests among Saudi patients. Saudi J Gastroenterol. 2023; 29(1): 31–8. DOI: https://doi.org/10.4103/sjg.sjg_280_22

Mills JR, Katzman BM, Ettore M, Murray JA, Gandhi MJ, Snyder MR. 72: Exploring Associations between genotype and serology in celiac disease. Am J Clin Pathol. 2015; 143 (suppl_1): A042–A042. DOI: https://doi.org/10.1 093/ajcp/143.suppl1.043

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. DOI: https://doi.org/10 .1097/MD.0000000000024954

Alam M, Tipu HN, Ahmad D, Hussain M, Khalid U Bin, Ijaz Y. HLA-DQ2 and HLA-DQ8 alleles in celiac disease patients and healthy controls. J Coll Physicians Surg Pak. 2022; 32(2): 157–60. DOI: https://doi.org/10.29271/jcpsp.2022.02.157

Schyum AC, Rumessen JJ. Serological testing for celiac disease in adults. United European Gastroenterol J. 2013; 1 (5): 319–25. DOI: https://doi.org/10.1177/2050640613502788

Ahmed Kiani R, Ahmed I, Khan Yousafzai J, Mehmood W, Ahmed Khan S, Ahmad W, et al. Celiac disease in different age groups and gender in Pakistan. JRMC. 2018; 22. Available from: https://www.journalrmc.com/index.php/JRMC/article/view/926

Raiteri A, Granito A, Giamperoli A, Catenaro T, Negrini G, Tovoli F. Current guidelines for the management of celiac disease: A systematic review with comparative analysis. World J Gastroenterol. 2022; 28(1): 154-75.

DOI: https://doi.org/10.3748/wjg.v28.i1.154

Haseeb A, Khattak AA, Hayat A, Rehman M, Jan F, Ahmed B, et al. Incidence and prevalence of celiac disease in Hazara Division, KP Pakistan by anti-tissue transglutaminase antibody as diagnostic tool. Pak J Med Health Sci. 2022; 16(12): 32–5. DOI: https://doi.org/10.53350/pjmhs2022161232

Khan MA, Jan H, Khan MO, Hanif M, Hassan T, Khurshid L. Prevalence of celiac disease in adult patients with iron deficiency anemia. Pak J Med Health Sci. 2022; 16(5): 1006–8. DOI: https://doi.org/10.53350/pjmhs221651006

Choung RS, Mills JR, Snyder MR, Murray JA, Gandhi MJ. Celiac disease risk stratification based on HLA-DQ heterodimer (HLA-DQA1 ~ DQB1) typing in a large cohort of adults with suspected celiac disease. Hum Immunol. 2020; 81(2): 59–64 DOI: https://doi.org/10.1016/j.humimm.2020.01.006

Leja M, Shums Z, Nikitina-Zake L, Gavars M, Kikuste I, Milo J, et al. Prevalence estimation of celiac disease in the general adult population of Latvia using serology and HLA genotyping. United European Gastroenterol J. 2015; 3(2): 190–9. DOI: https://doi.org/10.1177/2050640615569379

Dehghani SM, Dara N, Gharesifar B, Shahramian I, Dalili F, Salarzaei M. Prevalence of HLA DQ 2, 8 in children with celiac disease. Hum Antibodies. 2021; 29: 123–8. DOI: https://doi.org/10.3233/hab-200437

Lund F, Pedersen MF, Kristiansen S. Estimation of the celiac disease prevalence in Denmark and the diagnostic value of HLA-DQ2/ DQ8. Scand J Clin Lab Invest. 2020; 80(8): 667–71. DOI: https://doi.org/10.1080/00365513.2020.1829698

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): 351–9. DOI: https://doi.org/10.5409/wjcp.v11.i4.351

Shi T, Liu W, Li T, Liu H, Hui W, Lin Q, et al. HLA-DQ genotype distribution and risk evaluation of celiac disease in Northwest China. Scand J Gastroenterol. 2023; 58(5): 471–6. DOI: https://doi.org/10.1080/00365521.2022.2147801

Cecilio LA, Bonatto MW. The prevalence of HLA DQ2 and DQ8 in patients with celiac disease, in family and in general population. Arq Bras Cir Dig. 2015; 28(3): 183–5. DOI: https://doi.org/10.1590/S0102-67202015000 300009

Downloads

Published

29-03-2026

How to Cite

1.
Khan SW, Nawaz S, Hassan MA. Association of tissue transglutaminase IgA antibodies with HLA DQ2/DQ8 haplotypes in clinically suspected cases of celiac disease in Pakistani population. Pak J Pathol [Internet]. 2026 Mar. 29 [cited 2026 Oct. 28];37(1):1-5. Available from: https://pakjpath.com/index.php/Pak-J-Pathol/article/view/908

Issue

Vol. 37 No. 1 (2026): PAKISTAN JOURNAL OF PATHOLOGY (QUARTERLY)

Section

Articles

License

Copyright (c) 2026 Sara waqar khan, Sana Nawaz, Muhammad Aftab Hassan

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Readers may “Share-copy and redistribute the material in any medium or format” and “Adapt-remix, transform, and build upon the material”. The readers must give appropriate credit to the source of the material and indicate if changes were made to the material. Readers may not use the material for commercial purpose. The readers may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.