Histopathological Spectrum of Duodenal Biopsies in Seropositive Pediatric Celiac Disease: A Retrospective Study from Yazd, Iran

Articles in Press

Document Type : Original Article

Authors

Department of pathology, school of medicine, Shahid sadoughi hospital, Shahid Sadoughi University of medical sciences, Yazd, Iran

Abstract

Background: Celiac disease (CD) is an immune-mediated enteropathy triggered by gluten, with a global prevalence of approximately 1%. It is strongly associated with HLA-DQ2 and HLA-DQ8 haplotypes. Serological markers, particularly anti-tissue transglutaminase (tTG) immunoglobulin A (IgA), play a pivotal role in screening and diagnosis. This study aimed to evaluate the clinicopathological characteristics of duodenal biopsy specimens from patients with elevated serum tTG IgA levels.
Methods: This retrospective cross-sectional study analyzed 213 pediatric patients (age ≤16 years) with elevated anti-tTG IgA levels who underwent duodenal biopsy at Shahid Sadoughi Hospital, Iran (2016-2020). Demographic, clinical, and histopathological data were collected from medical records. Duodenal biopsies were classified using the Marsh-Oberhuber system. Statistical analysis was performed using SPSS version 22.
Results: The cohort consisted of 131 females (61.5%) and 82 males (38.5%), with a mean age of 5.9 years. The most common clinical manifestations were abdominal pain (58.7%) and failure to thrive (39%). Histopathological analysis revealed Marsh 3 lesions in 77% of cases (3a: 25.8%, 3b: 39.9%, 3c: 11.3%), while mild changes (Marsh 1-2) were observed in 23%. No significant association was found between Marsh classification and gender (p=0.36).
Conclusion: Elevated anti-tTG IgA levels strongly predict severe mucosal damage in pediatric celiac disease, suggesting the potential for reducing invasive biopsies through serology-based diagnosis. Validated antibody thresholds could enable less invasive diagnostic approaches.

Keywords

References

  1. Ludvigsson JF, Leffler DA, Bai JC, Biagi F, Fasano A, Green PH, et al. The Oslo definitions for coeliac disease and related terms. Gut. 2013;62(1):43-52.
  2. Edalatkhah R, Aflatooninan M, Firouzabadi BD, Fallah R. Evaluation of Frequency of Celiac Disease in Children with Idiopathic Epilepsy. Iranian Journal of Child Neurology. 2024;18(4):61.
  3. 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):88.
  4. Edalatkhah R, Rasoulizadeh Z, Mohammadi M, Aflatoonian M. Sleep Disorders in Children With Celiac Disease: An Analytic Cross-sectional Study. Caspian Journal of Neurological Sciences. 2025;11(3):230-6.
  5. Isa HM, Farid E, Makhlooq JJ, Mohamed AM, Al-Arayedh JG, Alahmed FA, et al. Celiac disease in children: increasing prevalence and changing clinical presentations. Clinical and Experimental Pediatrics. 2020;64(6):301.
  6. Donaldson MR, Firth SD, Wimpee H, Leiferman KM, Zone JJ, Horsley W, et al. Correlation of duodenal histology with tissue transglutaminase and endomysial antibody levels in pediatric celiac disease. Clinical Gastroenterology and Hepatology. 2007;5(5):567-73.
  7. Alessio MG, Tonutti E, Brusca I, Radice A, Licini L, Sonzogni A, et al. Correlation between IgA tissue transglutaminase antibody ratio and histological finding in celiac disease. Journal of pediatric gastroenterology and nutrition. 2012;55(1):44-9.
  8. Mubarak A, Wolters VM, Gmelig-Meyling FH, Ten Kate FJ, Houwen RH. Tissue transglutaminase levels above 100 U/mL and celiac disease: a prospective study. World Journal of Gastroenterology: WJG. 2012;18(32):4399.
  9. Zanini B, Magni A, Caselani F, Lanzarotto F, Carabellese N, Villanacci V, et al. High tissue-transglutaminase antibody level predicts small intestinal villous atrophy in adult patients at high risk of celiac disease. Digestive and Liver Disease. 2012;44(4):280-5.
  10. Barker CC, Mitton C, Jevon G, Mock T. Can tissue transglutaminase antibody titers replace small-bowel biopsy to diagnose celiac disease in select pediatric populations? Pediatrics. 2005;115(5):1341-6.
  11. Vivas S, de Morales JGR, Riestra S, Arias L, Fuentes D, Alvarez N, et al. Duodenal biopsy may be avoided when high transglutaminase antibody titers are present. World journal of gastroenterology: WJG. 2009;15(38):4775.
  12. Husby S, Koletzko S, Korponay‐Szabó I, Mearin M, Phillips A, Shamir R, et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. Journal of pediatric gastroenterology and nutrition. 2012;54(1):136-60.
  13. Wang M, Lu J, Li T, Ma C, Li Z, Abudurexiti A, et al. Association between anti-tissue transglutaminase antibody titers and duodenal histopathology among adults with celiac disease. Zhonghua nei ke za zhi. 2023;62(2):188-92.
  14. Fabiani E, Catassi C. The serum IgA class anti-tissue transglutaminase antibodies in the diagnosis and follow up of coeliac disease. Results of an international multi-centre study. European journal of gastroenterology & hepatology. 2001;13(6):659-65.
  15. Rahmati A, Shakeri R, Sohrabi M, Alipour A, Boghratian A, Setareh M, et al. Correlation of tissue transglutaminase antibody with duodenal histologic marsh grading. Middle East journal of digestive diseases. 2014;6(3):131.
  16. Majsiak E, Choina M, Gray AM, Wysokiński M, Cukrowska B. Clinical manifestation and diagnostic process of celiac disease in Poland—comparison of pediatric and adult patients in retrospective study. Nutrients. 2022;14(3):491.
  17. Parveen S, Hossain M, Sarker M, Raman M, Karim A. Histopathological Evaluation of Endoscopic Duodenal Biopsies in Children with Coeliac Disease and its Correlation with Tissue Transglutaminase Level. Mymensingh Medical Journal: MMJ. 2022;31(3):704-10.
  18. Kalhan S, Joseph P, Sharma S, Dubey S, Dudani S, Dixit M. Comparative study of histopathological Marsh grading with clinical and serological parameters in celiac iceberg of north India. Indian Journal of Pathology and Microbiology. 2011;54(2):279-83.
  19. Mahadev S, Laszkowska M, Sundström J, Björkholm M, Lebwohl B, Green PH, et al. Prevalence of celiac disease in patients with iron deficiency anemia—a systematic review with meta-analysis. Gastroenterology. 2018;155(2):374-82. e1.
  20. Beig J, Rostami K, Hayman DT, Hassan S, Gerred S, Ogra R. Is duodenal biopsy always necessary for the diagnosis of coeliac disease in adult patients with high anti-tissue transglutaminase (TTG) antibody titres? Frontline Gastroenterology. 2022;13(4):287-94.
World Journal of Peri & Neonatology

Articles in Press, Accepted Manuscript
Available Online from 11 November 2025

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  • Receive Date: 11 November 2025
  • Accept Date: 11 November 2025

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