Associação dos alelos de risco HLA-DQ2 e HLA-DQ8 à lesão intestinal e sorologia em pacientes com doença celíaca
Palavras-chave:
Enteropatia autoimmune, Marcadores genéticos, GlútenResumo
Objetivo
Este estudo tem como objetivo descrever a distribuição dos principais alelos de risco da doença celíaca relacionados ao complexo antígeno leucocitário humano e sua associação com a gravidade da lesão intestinal, resultados de testes sorológicos, doenças associadas à doença celíaca e sintomatologia.
Métodos
Foi analisado o DNA de 140 pacientes com doença celíaca e identificada a distribuição dos três alelos de risco mais importantes para o desenvolvimento de doença celíaca (DQA1*05:01, DQB1*02:01 e DRB1*04, sendo este o último um marcador para o aplótipo de risco DQB1*03:02/DQA1*03/DRB1*04). Os dados de exames sorológicos, resultados de biópsia, sintomatologia e incidência de doenças associadas à doença celíaca foram coletados por meio de questionário previamente validado.
Resultados
Verificou-se que 98% dos pacientes apresentavam pelo menos uma cópia dos alelos estudados. Pacientes portadores simultaneamente de ambos os alelos de risco HLA-DQ2 foram altamente prevalentes (75.0%), e 20,7% dos pacientes carregavam o haplótipo HLA-DQ8. Pacientes positivos para ambos os alelos de risco HLA-DQ2 apresentaram associação positiva aos testes sorológicos anti-gliadina (p=0,037), anti-endomísio (p=0,001) e anti-transglutaminase (p=0,032), e maior prevalência de osteoporose e hipotireoidismo. Pacientes portadores de um ou nenhum desses alelos frequentemente apresentavam resultados sorológicos negativos. Além disso, foi encontrada associação entre gravidade da lesão intestinal e perfil genético (p<0,001).
Conclusão
Os resultados sugerem que a genotipagem do HLA-DQ está associada aos testes sorológicos e à gravidade do dano intestinal em pacientes com doença celíaca.
Referências
Ludvigsson JF, Leffler DA, Bai JC, Biagi F, Fasano A, Green PHR, et al. The Oslo definitions for coeliac disease and related terms. Gut. 2013;62(1):43-52. http://dx.doi.org/10.1136/gutjnl-2011-301346
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):6302-8. http://dx.doi.org/10.3748/wjg.v20.i20.6302
Lionetti E, Catassi C. New clues in celiac disease epidemiology, pathogenesis, clinical manifestations, and treatment. Int Rev Immunol. 2011;30(4):219-31. http://dx.doi.org/10.3109/08830185.2011.602443
West J, Logan RFA, Hill PG, Khaw KT. The Iceberg of celiac disease: What is below the waterline? Clin Gastroenterol Hepatol. 2007;5(1):59-62. http://dx.doi.org/10.1016/j.cgh.2006.10.020
Rubio-Tapia A, Hill ID, Kelly CP, Calderwood AH, Murray JA. ACG clinical guidelines: Diagnosis and management of celiac disease. Am J Gastroenterol. 2013;108(5):656-76. http://dx.doi.org/10.1038/ajg.2013.79
Husby S, Koletzko S, Korponay-Szabó IR, Mearin ML, Phillips A, Shamir R, et al. European society for pediatric gastroenterology, hepatology, and nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr. 2012;54(1):136-60. http://dx.doi.org/10.1097/MPG.0b013e31821a23d0
Hanif FM, Kumar Mandhwani R, Hassan Luck N, Abbas Z, Mubarak M, Laeeq SM, et al. Clinicopathological study of seronegative celiac disease in adults in Pakistan: A pilot study. Middle East J Dig Dis. 2017;9(2):94-9. http://dx.doi.org/10.15171/mejdd.2017.57
Rostom A, Murray JA, Kagnoff MF. American Gastroenterological Association (AGA) Institute Technical Review on the Diagnosis and Management of Celiac Disease. Gastroenterology. 2006;131(6):1981-2002. http://dx.doi.org/10.1053/j.gastro.2006.10.004
Anderson RP, Henry MJ, Taylor R, Duncan EL, Danoy P, Costa MJ, et al. A novel serogenetic approach determines the community prevalence of celiac disease and informs improved diagnostic pathways. BMC Medicine. 2013;11(1). http://dx.doi.org/10.1186/1741-7015-11-188
Castro-Antunes MM, Crovella S, Brandão LAC, Guimarães RL, Motta MEFA, da Silva GAP. Frequency distribution of HLA DQ2 and DQ8 in celiac patients and first-degree relatives in Recife, northeastern Brazil. Clinics. 2011;66(2):227-31. http://dx.doi.org/10.1590/s1807-59322011000200008
Stanković B, Radlović N, Leković Z, Ristić D, Radlović V, Nikčević G, et al. HLA genotyping in pediatric celiac disease patients. Bosnian J Basic Med Sci. 2015;14(3):171-6. http://dx.doi.org/10.17305/bjbms.2014.3.28
Cassol CA, de Pellegrin CP, Wahys MLC, Pires MMDS, Nassar SM. Perfil clínico dos membros da associação dos celíacos do Brasil: Regional de Santa Catarina (ACELBRA-SC). Arq Gastroenterol. 2007;44(3):257-65. http://dx.doi.org/10.1590/S0004-28032007000300015
Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16(3):1215. http://dx.doi.org/10.1093/nar/16.3.1215
Aranalde LCR, Pederzoli BS, Marten T, Barros FC, Basso RP, Silveira JM, et al. The ACTN3 R577X polymorphism affects the lipid profile and the prognosis of nutritional intervention in HIV-positive patients. Nutr Res. 2016;36(6):564-74. http://dx.doi.org/10.1016/j.nutres.2016.02.002
Sacchetti L, Tinto N, Calcagno G, Improta P, Salvatore F. Multiplex PCR typing of the three most frequent HLA alleles in celiac disease. Clin Chim Acta. 2001;310(2):205-7. http://dx.doi.org/10.1016/s0009-8981(01)00575-7
Abadie V, Sollid LM, Barreiro LB, Jabri B. Integration of genetic and immunological insights into a model of celiac disease pathogenesis. Annu Rev Immunol. 2011;29:493-25.
Espino L, Núñez C. The HLA complex and coeliac disease. Int Rev Cell Mol Biol. 2021:358:47-83. https://doi.org/10.1016/bs.ircmb.2020.09.009. Epub 2020 Nov 11.
Marsh MN. Gluten, major histocompatibility complex, and the small intestine. A molecular and immunobiologic approach to the spectrum of gluten sensitivity (‘celiac sprue’). Gastroenterology. 1992;102(1):330-54.
Mills JR, Murray JA. Contemporary celiac disease diagnosis: Is a biopsy avoidable? Curr Opinion Gastroenterol. 2016;32(2):80-5. http://dx.doi.org/10.1097/MOG.0000000000000245
Fiori Nastro F, Serra MR, Cenni S, Pacella D, Martinelli M, Miele E, et al. Prevalence of functional gastrointestinal disorders in children with celiac disease on different types of gluten-free diets. World J Gastroenterol. 2022;28(46):6589-98. https://doi.org/10.3748/wjg.v28.i46.6589
Hadithi M, Blomberg BME von, Crusius JBA, Bloemena E, Kostense PJ, Meijer JWR, et al. Accuracy of Serologic Tests and HLA-DQ Typing for Diagnosing. Ann Intern Med. 2007;147(5):294-302. http://dx.doi.org/10.7326/0003-4819-147-5-200709040-00003
Murray JA, Moore SB, van Dyke CT, Lahr BD, Dierkhising RA, Zinsmeister AR, et al. HLA DQ Gene dosage and risk and severity of celiac disease. Clin Gastroenterol Hepatol. 2007;5(12):1406-12. http://dx.doi.org/10.1016/j.cgh.2007.08.013
Mashayekhi K, Rostami-Nejad M. The correlation between HLA-DQ2 and HLA-DQ8 haplotypes and abnormal histology in patients with celiac disease. Int Anal Pharm Biomed Sci. 2015;4:152-6.
Tinto N, Cola A, Piscopo C, Capuano M, Galatola M, Greco L, et al. High frequency of haplotype HLA-DQ7 in celiac disease patients from south Italy: Retrospective evaluation of 5,535 subjects at risk of celiac disease. Plos One. 2015;10(9):1-7. http://dx.doi.org/10.1371/journal.pone.0138324
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. Przeglad Gastroenterol. 2017;12(4):256-61. http://dx.doi.org/ 10.5114/pg.2017.72099
Saeed A, Assiri A, Assiri H, Ullah A, Rashid M. Celiac disease in Saudi children: Evaluation of clinical features and diagnosis. Saudi Med J. 2017;38(9):895-9. http://dx.doi.org/10.15537/smj.2017.9.20808
Abenavoli L, Delibasic M, Peta V, Turkulov V, De Lorenzo A, Medić-Stojanoska M. Nutritional profile of adult patients with celiac disease. Eur Revr Med Pharmacol Sci. 2015;19:4285-92.
Lauret E, Rodrigo L. Celiac disease and autoimmune-associated conditions. Biomed Res Int. 2013;2013:127589. http://dx.doi.org/10.1155/2013/127589
Bliddal S, Nielsen CH, Feldt-Rasmussen U. Recent advances in understanding autoimmune thyroid disease: The tallest tree in the forest of polyautoimmunity. F1000 Res. 2017;6(0):1-12. http://dx.doi.org/10.12688/f1000research.11535.1.eCollection 2017
Downloads
Publicado
Como Citar
Edição
Seção
Licença
Copyright (c) 2025 Mônica Schiavon Costa, Giovana Ribeiro Pegoraro, Clédia Silveira Flores da Silva, Augusto Schneider, Ines Schadock, Fabiana Torma Botelho, Carlos Castilho Barros
Este trabalho está licenciado sob uma licença Creative Commons Attribution 4.0 International License.
