MOLECULAR AND IMMUNOLOGICAL STUDY OF CELIAC DISEASE IN SAMPLES OF IRAQI PATIENTS



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Aim: Evaluation of Human Leukocyte Antigen (HLA) DQ2/DQ8 in celiac disease (CD) patients compared to healthy controls, and  to investigate the presence of specific immunological markers (IL-15, IL-21, and TNFα) in the human serum samples from the study groups, also to detect HLA-DQ2 and HLADQ8 in relation to interleukins IL-15, IL-21, and TNF in CD patients.

Methods: A total of 90 individuals participated in this study, comprising 50 patients clinically and serologically diagnosed with celiac disease and 40 apparently healthy individuals serving as the control group. The participants were carefully selected and matched for age and gender where possible. Genotyping for HLA-DQ2 and HLA-DQ8 was conducted using the polymerase chain reaction (PCR) technique, which allows for accurate detection of specific alleles associated with genetic susceptibility to CD. In addition, enzyme-linked immunosorbent assay (ELISA) was employed to determine the serum concentrations of IL-15, IL-21, and TNF-α in both patient and control groups. Statistical analyses were performed to assess the significance of differences observed between the groups and to explore the relationship between HLA genotypes and cytokine expression levels.

Results: The individuals in the case study group were aged between 1 and 60 years. In terms of gender, the patient group consisted of 18 (36.0%) males and 32 (64.0%) females. Among 50 patients with celiac disease, 76.0% had HLA-DQ2, 20.0% had HLA-DQ8, and 14.0% had both. The majority of alleles encoded for HLADQ2 were significant in CD patients when compared with controls. The serum concentrations of IL-15, TNF-α, and IL-21 in the sick group were statistically significant with P-values of 0.001, 0.018, and 0.0001, respectively.

Conclusion: The HLADQ2 genotype is the most common HLA genotype among celiac patients in Iraq, followed by HLADQ8. Serum levels of IL-15, IL-21, and TNF-α were considerably elevated in individuals with CD compared to the control group.

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Об авторах

Sardar Khudhur

Cankiri Karatekin University, Cankiri, Turkey

Email: sardarturk88@gmail.com
ORCID iD: 0009-0000-3443-4577

Academic Degree: BSc., MSc., PhD. in Molecular Biology

Academic Title: Assistant Professor (or specify actual title)

Tenure: Faculty member, Department of Biology, Cankiri Karatekin University

Molecular Biology in Department of Biology, Faculty of Science, Cankiri Karatekin University, Cankiri, Turkey;

Турция

Özcan Özkan

Cankiri Karatekin University, Cankiri, Turkey

Email: ozcanozkan@karatekin.edu.tr
ORCID iD: 0000-0002-5216-8361

Academic Title: Associate Professor (or specify actual title)

Tenure: Faculty member, Department of Biology, Cankiri Karatekin University

Department of Biology, Faculty of Science, Cankiri Karatekin University, Cankiri, Turkey;

Турция

Jaleel Samanje

Middle Technical University, Baghdad, Iraq

Автор, ответственный за переписку.
Email: jaleel.najah@mtu.edu.iq
ORCID iD: 0000-0001-9747-8120

Academic Degree: PhD.

Academic Title: Lecturer

Tenure: Faculty member, Middle Technical University

Colleague of Health and Medical Techniques, Middle Technical University, Baghdad, Iraq;

Ирак

Список литературы

  1. Voisine J, Abadie V. Interplay Between Gluten, HLA, Innate and Adaptive Immunity Orchestrates the Development of Coeliac Disease. Front Immunol. 2021 Jun 2;12:674313. doi: 10.3389/fimmu.2021.674313. PMID: 34149709; PMCID: PMC8206552.
  2. Caio G, Volta U, Sapone A, Leffler DA, De Giorgio R, Catassi C, Fasano A. Celiac disease: a comprehensive current review. BMC Med. 2019 Jul 23;17(1):142. doi: 10.1186/s12916-019-1380-z. PMID: 31331324; PMCID: PMC6647104.
  3. Gudjónsdóttir AH, Nilsson S, Naluai AT, Ek J, Amundsen SS, Wahlström J, Ascher H. Association between genotypes and phenotypes in coeliac disease. J Pediatr Gastroenterol Nutr. 2009 Aug;49(2):165-9. doi: 10.1097/MPG.0b013e318196c362. PMID: 19543113.
  4. Martínez-Ojinaga E, Molina M, Polanco I, Urcelay E, Núñez C. HLA-DQ distribution and risk assessment of celiac disease in a Spanish center. Rev Esp Enferm Dig. 2018 Jul;110(7):421-426. doi: 10.17235/reed.2018.5399/2017. PMID: 29699404.
  5. Smigoc Schweiger D, Mendez A, Kunilo Jamnik S, Bratanic N, Bratina N, Battelino T, Brecelj J, Vidan-Jeras B. High-risk genotypes HLA-DR3-DQ2/DR3-DQ2 and DR3-DQ2/DR4-DQ8 in co-occurrence of type 1 diabetes and celiac disease. Autoimmunity. 2016 Jun;49(4):240-7. doi: 10.3109/08916934.2016.1164144. Epub 2016 Apr 20. PMID: 27138053.
  6. Hammo S, Al-Nuaimy WMT, Hayawi M. The significance of CD3 marker in the diagnosis of celiac disease. Ann Coll Med Mosul. 2020;42(2):99–100. https://pdfs.semanticscholar.org/cbd8/663d28f5161216d535462250824439b0239d.pdf
  7. Al-Kemawy SNY, Al-Saltani SNH. Serological tests assessment in patients suspected to have celiac disease attending the Gastroenterology and Hepatology Teaching Hospital in Baghdad. 2024. https://bmjpaedsopen.bmj.com/content/8/Suppl_4/A6.3
  8. Dixit R, Lebwohl B, Ludvigsson JF, Lewis SK, Rizkalla-Reilly N, Green PH. Celiac disease is diagnosed less frequently in young adult males. Dig Dis Sci. 2014 Jul;59(7):1509-12.. doi: 10.1007/s10620-014-3025-6. Epub 2014 Jan 21. PMID: 24445731
  9. 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 Jul-Sep;28(3):183-5. doi: 10.1590/S0102-67202015000300009. PMID: 26537142; PMCID: PMC4737358.
  10. Falcigno L, Calvanese L, Conte M, Nanayakkara M, Barone MV, D'Auria G. Structural Perspective of Gliadin Peptides Active in Celiac Disease. Int J Mol Sci. 2020 Dec 6;21(23):9301. doi: 10.3390/ijms21239301. PMID: 33291297; PMCID: PMC7731278.
  11. Maruntelu I, Preda CM, Sandra I, Istratescu D, Chifulescu AE, Manuc M, Diculescu M, Talangescu A, Tugui L, Manuc T, Stroie T, Andrei AC, Tieranu C, Constantinescu I. HLA Genotyping in Romanian Adult Patients with Celiac Disease, their First-degree Relatives and Healthy Persons. J Gastrointestin Liver Dis. 2022 Jun 12;31(2):191-197. doi: 10.15403/jgld-4187. PMID: 35694992.
  12. Fernández-Cavada-Pollo MJ, Alcalá-Peña MI, Vargas-Pérez ML, Vergara-Prieto E, Vallcorba-Gómez-Del Valle I, Melero-Ruiz J, Márquez-Armenteros AM, Romero-Albillos JA, Narváez-Rodríguez I, Fernández-de-Mera JJ, González-Roiz C. Celiac disease and HLA-DQ genotype: diagnosis of different genetic risk profiles related to the age in Badajoz, southwestern Spain. Rev Esp Enferm Dig. 2013 Sep;105(8):469-76. doi: 10.4321/s1130-01082013000800005. PMID: 24274444.
  13. Giriprasad V, Mechenro J, Balamurugan R, Ramakrishna BS. Frequency of HLA celiac disease risk alleles and haplotypes in healthy adults in Tamil Nadu. Indian J Gastroenterol. 2019 Apr;38(2):178-182. doi: 10.1007/s12664-019-00947-6. Epub 2019 Apr 26. PMID: 31025255.
  14. Özgenel ŞM, Temel T, Üsküdar Teke H, 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. Turk J Gastroenterol. 2019 Apr;30(4):321-325. doi: 10.5152/tjg.2019.18255. PMID: 30945642; PMCID: PMC6453657.
  15. Mansouri M, Dadfar M, Rostami-Nejad M, Ekhlasi G, Shahbazkhani A, Shahbazkhani B. The frequency of HLA-DQ2/DQ8 haplotypes and celiac disease among the first-degree relatives of patients with celiac disease. Gastroenterol Hepatol Bed Bench. 2021 Winter;14(1):36-43. PMID: 33868608; PMCID: PMC8035532. https://pmc.ncbi.nlm.nih.gov/articles/PMC8035532/
  16. Talib EQ, Taha GI. Involvement of interlukin-17A (IL-17A) gene polymorphism and interlukin-23 (IL-23) level in the development of peri-implantitis. BDJ Open. 2024 Feb 28;10(1):12. doi: 10.1038/s41405-024-00193-9. PMID: 38413570; PMCID: PMC10899656.
  17. 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. Prz Gastroenterol. 2017;12(4):256-261. doi: 10.5114/pg.2017.72099. Epub 2017 Dec 14. PMID: 29358994; PMCID: PMC5771449.
  18. 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 (Baltimore). 2021 Mar 19;100(11):e24954. doi: 10.1097/MD.0000000000024954. PMID: 33725967; PMCID: PMC7982179.
  19. Çakır M, Baran M, Uçar F, Akbulut UE, Kaklıkkaya N, Ersöz Ş. Accuracy of HLA-DQ genotyping in combination with IgA anti-tissue transglutaminase serology and a "scoring system" for the diagnosis of celiac disease in Turkish children. Turk J Pediatr. 2014 Jul-Aug;56(4):347-53. PMID: 25818952. https://turkjpediatr.org/article/view/1382
  20. Fernández-Mestre M, Padrón-Lowe D, Salazar-Alcalá E, Blanco-Pérez F. Role of HLA-DQB1 alleles in the risk, signs and symptoms, and severity of celiac disease in a Venezuelan population. Rev Gastroenterol Mex (Engl Ed). 2023 Apr-Jun;88(2):125-131. doi: 10.1016/j.rgmxen.2022.03.008. Epub 2022 May 3. PMID: 35523683.
  21. Martínez-Ojinaga E, Molina M, Polanco I, Urcelay E, Núñez C. HLA-DQ distribution and risk assessment of celiac disease in a Spanish center. Rev Esp Enferm Dig. 2018 Jul;110(7):421-426.. doi: 10.17235/reed.2018.5399/2017. PMID: 29699404
  22. Wiebe C, Kosmoliaptsis V, Pochinco D, Gibson IW, Ho J, Birk PE, Goldberg A, Karpinski M, Shaw J, Rush DN, Nickerson PW. HLA-DR/DQ molecular mismatch: A prognostic biomarker for primary alloimmunity. Am J Transplant. 2019 Jun;19(6):1708-1719. doi: 10.1111/ajt.15177. Epub 2018 Dec 15. PMID: 30414349; PMCID: PMC6563434.
  23. Maruntelu I, Preda CM, Sandra I, Istratescu D, Chifulescu AE, Manuc M, Diculescu M, Talangescu A, Tugui L, Manuc T, Stroie T, Andrei AC, Tieranu C, Constantinescu I. HLA Genotyping in Romanian Adult Patients with Celiac Disease, their First-degree Relatives and Healthy Persons. J Gastrointestin Liver Dis. 2022 Jun 12;31(2):191-197. doi: 10.15403/jgld-4187. PMID: 35694992.
  24. Ramakrishna BS, Venugopal G, Singh A, Pugazhendhi S, Dutta S, Ahuja V, Makharia GK. Human Leukocyte Antigen DQ (HLA-DQ) genotypes and haplotypes and their association with phenotype in patients with celiac disease in India. JGH Open. 2021 Sep 1;5(10):1190-1196. doi: 10.1002/jgh3.12651. PMID: 34622007; PMCID: PMC8485407
  25. Zamani M, Modares-Sadegi M, Shirvani F, Zamani H, Emami MH. The involvement of the HLA-DQB1 alleles in the risk and the severity of Iranian coeliac disease patients. Int J Immunogenet. 2014 Aug;41(4):312-7. doi: 10.1111/iji.12128. Epub 2014 Jun 11. PMID: 24917237.
  26. Manavalan JS, Hernandez L, Shah JG, Konikkara J, Naiyer AJ, Lee AR, Ciaccio E, Minaya MT, Green PH, Bhagat G. Serum cytokine elevations in celiac disease: association with disease presentation. Hum Immunol. 2010 Jan;71(1):50-7. doi: 10.1016/j.humimm.2009.09.351. PMID: 19735687.
  27. Borges MD, Franca EL, Fujimori M, Silva SMC, de Marchi PGF, Deluque AL, Honorio-Franca AC, de Abreu LC. Relationship between Proinflammatory Cytokines/Chemokines and Adipokines in Serum of Young Adults with Obesity. Endocr Metab Immune Disord Drug Targets. 2018;18(3):260-267. doi: 10.2174/1871530318666180131094733. PMID: 29384066.
  28. Di Sabatino A, Giuffrida P, Fornasa G, Salvatore C, Vanoli A, Naviglio S, De Leo L, Pasini A, De Amici M, Alvisi C, Not T, Rescigno M, Corazza GR. Innate and adaptive immunity in self-reported nonceliac gluten sensitivity versus celiac disease. Dig Liver Dis. 2016 Jul;48(7):745-52. doi: 10.1016/j.dld.2016.03.024. Epub 2016 Apr 7. PMID: 27130911.
  29. Heydari F, Rostami-Nejad M, Moheb-Alian A, Mollahoseini MH, Rostami K, Pourhoseingholi MA, Aghamohammadi E, Zali MR. Serum cytokines profile in treated celiac disease compared with non-celiac gluten sensitivity and control: a marker for differentiation. J Gastrointestin Liver Dis. 2018 Sep;27(3):241-247. doi: 10.15403/jgld.2014.1121.273.hey. PMID: 30240467.
  30. Babania O, Mohammadi S, Yaghoubi E, Sohrabi A, Sadat Seyedhosseini F, Abdolahi N, Yazdani Y. The expansion of CD14+ CD163+ subpopulation of monocytes and myeloid cells-associated cytokine imbalance; candidate diagnostic biomarkers for celiac disease (CD). J Clin Lab Anal. 2021 Oct;35(10):e23984. doi: 10.1002/jcla.23984. Epub 2021 Aug 27. PMID: 34449925; PMCID: PMC8529138.
  31. Iervasi E, Auricchio R, Strangio A, Greco L, Saverino D. Serum IL-21 levels from celiac disease patients correlates with anti-tTG IgA autoantibodies and mucosal damage. Autoimmunity. 2020 Jun;53(4):225-230. doi: 10.1080/08916934.2020.1736047. Epub 2020 Mar 11. PMID: 32157915.
  32. Borrelli M, Gianfrani C, Lania G, Aitoro R, Ferrara K, Nanayakkara M, Ponticelli D, Zanzi D, Discepolo V, Vitale S, Barone MV, Troncone R, Auricchio R, Maglio M. In the Intestinal Mucosa of Children With Potential Celiac Disease IL-21 and IL-17A are Less Expressed than in the Active Disease. Am J Gastroenterol. 2016 Jan;111(1):134-44. doi: 10.1038/ajg.2015.390. Epub 2016 Jan 12. PMID: 26753888.
  33. Galatola M, Izzo V, Cielo D, Morelli M, Gambino G, Zanzi D, Strisciuglio C, Sperandeo MP, Greco L, Auricchio R. Gene expression profile of peripheral blood monocytes: a step towards the molecular diagnosis of celiac disease? PLoS One. 2013 Sep 17;8(9):e74747. doi: 10.1371/journal.pone.0074747. PMID: 24069342; PMCID: PMC3775745.
  34. Mazzarella G. Effector and suppressor T cells in celiac disease. World J Gastroenterol. 2015 Jun 28;21(24):7349-56. doi: 10.3748/wjg.v21.i24.7349. PMID: 26139981; PMCID: PMC4481430.
  35. Shannahan S, Leffler DA. Diagnosis and Updates in Celiac Disease. Gastrointest Endosc Clin N Am. 2017 Jan;27(1):79-92.. doi: 10.1016/j.giec.2016.08.011. PMID: 27908520
  36. Goel G, Daveson AJM, Hooi CE, Tye-Din JA, Wang S, Szymczak E, Williams LJ, Dzuris JL, Neff KM, Truitt KE, Anderson RP. Serum cytokines elevated during gluten-mediated cytokine release in coeliac disease. Clin Exp Immunol. 2020 Jan;199(1):68-78. doi: 10.1111/cei.13369. Epub 2019 Oct 1. PMID: 31505020; PMCID: PMC6904604.
  37. Ajdani M, Mortazavi N, Besharat S, Mohammadi S, Amiriani T, Sohrabi A, Norouzi A, Edris G. Serum and salivary tissue transglutaminase IGA (tTG-IGA) level in celiac patients. BMC Gastroenterol. 2022 Aug 6;22(1):375. doi: 10.1186/s12876-022-02456-x. PMID: 35933327; PMCID: PMC9357310.
  38. Faghih M, Rostami-Nejad M, Amani D, Sadeghi A, Pourhoseingholi MA, Masotti A, Zali MR. Analysis of IL17A and IL21 Expression in the Small Intestine of Celiac Disease Patients and Correlation with Circulating Thioredoxin Level. Genet Test Mol Biomarkers. 2018 Sep;22(9):518-525.
  39. doi: 10.1089/gtmb.2018.0128. Epub 2018 Sep 5. PMID: 30183349.

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