- All Journals
- Al-Qadisiyah University
- Basrah University
- Kirkuk University
- Mosul University
- The Iraqi Borad for Medical Specialization
- University of Anbar
- University of Technology
- Al Mustafa University
- Al-Zahraa University for Women
- Alnoor University
- Kunooz University
- Misan University
- Ninevah University
- Tikrit University
- University of Al-Hamdaniya
- University of Kerbala
Role of heat shock proteins and autoantibodies as biomarkers in advanced grade celiac disease | ||
| Journal of University of Anbar for Pure Science | ||
| Volume 20, Issue 2, August 2026, Pages 112-122 PDF (1.98 M) | ||
| Document Type: Research Paper | ||
| DOI: 10.37652/juaps.2025.162648.1693 | ||
| Authors | ||
| Hiba Ali Abdulsattar* 1; Yasir M. Abdulateef2; Ahmad Sami Farhan1 | ||
| 1Biology Department, College of Science, University of Anbar, Anbar, Iraq | ||
| 2Medical Microbiology Department, Medical College, University of Anbar, Anbar, Iraq | ||
| Abstract | ||
| Celiac disease is an autoimmune-mediated disorder triggered by gluten consumption in genetically predisposed individuals, leading to villous atrophy and malabsorption. Although duodenal biopsy remains a key diagnostic tool, the role of heat shock proteins (HSPs) in mucosal injury and recovery has not been fully clarified. This study aimed to examine the relationship between celiac disease-specific autoantibodies and the expression levels of heat shock proteins (HSP70, HSP72, and HSP75) in patients with celiac disease and to correlate these findings with histopathological grades (Marsh 3A–3C). This case-control study included 64 newly diagnosed patients with celiac disease and 26 non-celiac controls from Al-Anbar Governorate, Iraq. Serum anti-tissue transglutaminase antibodies (tTG-IgA and tTG-IgG), anti-gliadin antibodies (IgA and IgG), and anti-deamidated gliadin peptide antibodies (DGP-IgA and DGP-IgG) were measured by ELISA using the Chorus TRIO system. Serum HSP70 and HSP72 levels were measured by ELISA, whereas HSP70, HSP72, and HSP75 expression in duodenal biopsies was assessed by immunohistochemistry (IHC) according to the Marsh–Oberhuber classification. Statistical analysis was performed using SPSS version 29.0, with significance set at p < 0.05. All measured autoantibodies and serum HSP markers were significantly higher in patients with celiac disease than in controls (p < 0.05). The severity of mucosal damage was associated with increasing antibody titers, with the highest levels observed in Marsh 3C cases. Serum HSP70 and HSP72 levels were generally increased in patients with celiac disease; however, they did not differ significantly among the Marsh subgroups. IHC analysis showed that HSP70 and HSP72 expression decreased with increasing villous atrophy, while HSP75 expression showed no significant trend. Celiac disease-specific autoantibodies were strongly associated with histological severity, supporting their use as practical non-invasive biomarkers. Changes in HSP70 and HSP72 expression suggest their involvement in mucosal stress responses and disease progression, indicating their potential value as future therapeutic or predictive biomarkers in celiac disease. | ||
| Keywords | ||
| Celiac disease; Heat shock proteins; Serological biomarkers | ||
| References | ||
|
[1] Abbasi A, Bazzaz S, Ibrahim SA, Hekmatdoost A, Hosseini H, Sabahi S, et al. A Critical Review on the Gluten-Induced Enteropathy/Celiac Disease: Gluten-Targeted Dietary and Non-Dietary Therapeutic Approaches. Food Reviews International. 2024;40(3):883-923. 10.1080/87559129.2023.2202405 [2] Brown I, Bettington M, Rosty C. The Role of Histopathology in the Diagnosis and Management of Coeliac Disease and Other Malabsorptive Conditions.Histopathology. 2021;78(1):88-105. 10.1111/his.14262 [3] Mędza A, Szlagatys-Sidorkiewicz A. Nutritional Status and Metabolism in Celiac Disease: Narrative Review. Journal of Clinical Medicine. 2023;12(15):5107.10.3390/jcm12155107 [4] Lebwohl B, Rubio-Tapia A. Epidemiology, Presentation, and Diagnosis of Celiac Disease. Gastroenterology. 2021;160(1):63–75. 10.1053/j.gastro.2020.06.098 [5] Simón E, Molero-Luis M, Fueyo-Díaz R, Costas-Batlle C, Crespo-Escobar P, Montoro-Huguet MA. The Gluten-Free Diet for Celiac Disease: Critical Insights to Better Understand Clinical Outcomes. Nutrients. 2023;15(18):4013.10.3390/nu15184013 [6] Voisine J, Abadie V. Interplay Between Gluten, HLA, Innate and Adaptive Immunity Orchestrates the Development of Coeliac Disease.Frontiers in Immunology. 2021;12.10.3389/fimmu.2021.674313 [7] Dunne MR, Byrne G, Chirdo FG, Feighery C. Coeliac Disease Pathogenesis: The Uncertainties of a Well-Known Immune Mediated Disorder. Frontiers in Immunology. 2020;11. 10.3389/fimmu.2020.01374 [8] Doyle JB, Silvester J, Ludvigsson JF, Lebwohl B.Advances in the pathophysiology, diagnosis, and management of celiac disease.BMJ. 2025;391:e081353. 10.1136/bmj-2024-081353 [9] Elli L, Leffler D, Cellier C, Lebwohl B, Ciacci C, Schumann M, et al. Guidelines for Best Practices in Monitoring Established Coeliac Disease in Adult Patients.Nature Reviews Gastroenterology & Hepatology. 2024;21(3):198-215.10.1038/s41575-023-00872-2 [10] Robert ME, Ciacci C, Lebwohl B. Opportunities for Improving Biopsy and Non–Biopsy-Based Diagnosis of Celiac Disease. Gastroenterology. 2024;167(1):79–89.10.1053/j.gastro.2024.01.031 [11] Ghafoor M, Ikram F, Zaman S, Bashir J, Tabassum S, Babar MW. Celiac Disease Investigation with Marsh Classification in Paediatric Population. Pakistan Armed Forces Medical Journal. 2022;72(4):1164–67.10.51253/pafmj.v72i4.7212 [12] Das P, Makharia G, Datta Gupta S. In: Pathology of Malabsorption Syndrome. Springer Singapore; 2022. p. 279–338.10.1007/978-981-16-6395-6_9 [13] Patel N, Leffler DA, Al-Toma A, Mulder CJ, Elli L, Gan G, et al.Clinical Data Do Not Reliably Predict Duodenal Histology at Follow-up in Celiac Disease: A 13 Center Correlative Study.The American Journal of Surgical Pathology. 2024 feb;48(2):212-20. 10.1097/PAS.0000000000002150 [14] Adams DW, Moleski S, Jossen J, Tye-Din JA.Clinical Presentation and Spectrum of Gluten Symptomatology in Celiac Disease. Gastroenterology. 2024.10.1053/j.gastro.2024.01.052 [15] Wieser H, Segura V, Ruiz-Carnicer A, Sousa C, Comino I.Food Safety and Cross-Contamination of Gluten-Free Products: A Narrative Review.Nutrients. 2021;13(7):2244.10.3390/nu13072244 [16] Szaflarska-Popławska A.Wait-and-See Approach or Gluten-Free Diet Administration—The Rational Management of Potential Coeliac Disease.Nutrients. 2021;13(3):947.10.3390/nu13030947 [17] Catassi GN, Pulvirenti A, Monachesi C, Catassi C, Lionetti E. Diagnostic Accuracy of IgA Anti-Transglutaminase and IgG Anti-Deamidated Gliadin for Diagnosis of Celiac Disease in Children under Two Years of Age: A Systematic Review and Meta-Analysis. Nutrients. 2021;14(1):7. 10.3390/nu14010007 [18] Horton RK, Hagen CE, Snyder MR. Pediatric Celiac Disease: A Review of Diagnostic Testing and Guideline Recommendations. The Journal of Applied Laboratory Medicine. 2022;7(1):294–304. 10.1093/jalm/jfab143 [19] Jahdkaran M, Asri N, Esmaily H, Rostami-Nejad M. Potential of Nutraceuticals in Celiac Disease. Tissue Barriers. 2025;13(2):2374628. 10.1080/21688370.2024.2374628 [20] Vona R, Pallotta L, Cappelletti M, Severi C, Matarese P. The Impact of Oxidative Stress in Human Pathology: Focus on Gastrointestinal Disorders.Antioxidants. 2021;10(2):201.10.3390/antiox10020201 [21] Li G, Wang S, Fan Z. Oxidative Stress in Intestinal Ischemia-Reperfusion. Frontiers in Medicine. 2022;8.10.3389/fmed.2021.750731 [22] Glineburg MR, Nguyen C.Diverse roles of stress-responsive RNP granules in oogenesis and infertility. Biology of Reproduction. 2025;112(6):1039–1053. 10.1093/biolre/ioaf057 [23] Hu C, Yang J, Qi Z, Wu H, Wang B, Zou F, et al.Heat shock proteins: Biological functions, pathological roles, and therapeutic opportunities. MedComm. 2022;3(3).10.1002/mco2.161 [24] Singh MK, Han S, Ju S, Ranbhise JS, Ha J, Yeo SG, et al. Hsp70: A Multifunctional Chaperone in Maintaining Proteostasis and Its Implications in Human Disease. Cells. 2025;14(7):509. 10.3390/cells14070509 [25] Hoter A, Naim HY. The Functions and Therapeutic Potential of Heat Shock Proteins in Inflammatory Bowel Disease—An Update. International Journal of Molecular Sciences. 2019;20(21):5331. 10.3390/ijms20215331 [26] Bottoni P, Giardina B, Scatena R.Proteomic profiling of heat shock proteins: An emerging molecular approach with direct pathophysiological and clinical implications. PROTEOMICS – Clinical Applications. 2009;3(6):636–653.10.1002/prca.200800195 [27] Partanen J, Milner C, Campbell RD, Mäki M, Lipsanen V, Koskimies S.HLA-linked heat-shock protein 70 (HSP70–2) gene polymorphism and celiac disease.Tissue Antigens. 1993;41(1):15–19. 10.1111/j.1399-0039.1993.tb01971.x [28] Scalia F, Carini F, David S, Giammanco M, Mazzola M, Rappa F, et al. Inflammatory Bowel Diseases: An Updated Overview on the Heat Shock Protein Involvement.International Journal of Molecular Sciences. 2023;24(15):12129.10.3390/ijms241512129 [29] Hao D, Li Y, Shi J, Jiang J. Baicalin alleviates chronic obstructive pulmonary disease through regulation of HSP72-mediated JNK pathway.Molecular Medicine. 2021;27(1).10.1186/s10020-021-00309-z [30] Rossi G. In: New Acquisitions Regarding Structure and Function of Intestinal Mucosal Barrier. IntechOpen; 2022. 10.5772/intechopen.105463 [31] Albakova Z, Mangasarova Y, Albakov A, Gorenkova L. HSP70 and HSP90 in Cancer: Cytosolic, Endoplasmic Reticulum and Mitochondrial Chaperones of Tumorigenesis. Frontiers in Oncology. 2022;12:829520.10.3389/fonc.2022.829520 [32] Ghulam Mohyuddin S, Khan I, Zada A, Qamar A, Arbab AAI, Ma Xb, et al. Influence of Heat Stress on Intestinal Epithelial Barrier Function, Tight Junction Protein, and Immune and Reproductive Physiology.BioMed Research International. 2022;2022:8547379.10.1155/2022/8547379 | ||
|
Statistics Article View: 116 PDF Download: 346 |
||