Клиническое значение антител при воспалительных заболеваниях кишечника - Журнал Терапевтический архив №2 Вопросы гастроэнтерологии 2021

Клиническое значение антител при воспалительных заболеваниях кишечника

Александрова Е.Н., Новиков А.А., Лукина Г.В., Парфенов А.И. Клиническое значение антител при воспалительных заболеваниях кишечника. Терапевтический архив. 2021; 93 (2): 228–235. DOI: 10.26442/00403660.2021.02.200610

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Aleksandrova E.N., Novikov A.A., Lukina G.V., Parfenov A.I. Clinical value of antibodies in inflammatory bowel diseases. Terapevticheskii Arkhiv (Ter. Arkh.). 2021; 93 (2): 228–235. DOI: 10.26442/00403660.2021.02.200610

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Аннотация

Воспалительные заболевания кишечника – ВЗК (болезнь Крона – БК, язвенный колит – ЯК) – иммуноопосредованные болезни неизвестной этиологии. В основе патогенеза ВЗК лежат нарушение барьерной функции кишечника по отношению к антигенам микробного и пищевого происхождения, генетическая предрасположенность и дефекты активации иммунного ответа в лимфоидной ткани слизистой оболочки кишки. В сыворотках больных ВЗК выявляют 3 группы антител: аутоантитела, антимикробные антитела и антитела к пептидным антигенам. При БК наиболее полезными диагностическими маркерами являются антитела к хлебопекарным и пивным дрожжам Saccharomyces cerevisiae, при ЯК – перинуклеарные антинейтрофильные цитоплазматические антитела. Антитела не входят в число диагностических критериев БК и ЯК, диагноз которых традиционно ставится на основании комплекса клинических, рентгенологических, эндоскопических и гистологических признаков, однако могут использоваться в качестве полезных дополнительных неинвазивных маркеров для ранней диагностики, оценки клинических фенотипов, прогноза и эффективности терапии данных заболеваний.

Ключевые слова: воспалительные заболевания кишечника, болезнь Крона, язвенный колит, аутоантитела, антимикробные антитела, антитела к пептидным антигенам, диагностическое и прогностическое значение

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Inflammatory bowel disease – IBD (Crohn’s disease – CD, ulcerative colitis – UC) – immune-mediated diseases of the digestive tract of unknown etiology. The basis of the pathogenesis of IBD is a violation of the protective mechanisms of the intestinal barrier as a result of a complex interaction of environmental factors, a genetic predisposition and defects in the activation of the immune response in the lymphoid tissue of the intestinal mucosa. Three groups of antibodies are detected in the sera of IBD patients: autoantibodies, antimicrobial antibodies and antibodies to peptide antigens. In CD, the most useful diagnostic markers are ASCA; in UC patients – pANCA. Antibodies are not among the diagnostic criteria for CD and UC, the diagnosis of which is traditionally made on the basis of a complex of clinical, radiological, endoscopic and histological signs, but can be used as useful additional non-invasive markers for early diagnosis, assessment of clinical phenotypes, prognosis and effectiveness of treatment of these diseases.

Keywords: inflammatory bowel disease, Crohn’s disease, ulcerative colitis, autoantibodies, antimicrobial antibodies, antibodies to peptide antigens, diagnostic and prognostic value

Список литературы

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2. Ивашкин В.Т., Шелыгин Ю.А., Халиф И.Л. и др. Клинические рекомендации Российской гастроэнтерологической ассоциации и Ассоциации колопроктологов России по диагностике и лечению язвенного колита. Колопроктология. 2017;1:6-30 [Ivashkin VT, Shelygin IuA, Khalif IL, et al. Clinical guide of Russian association of gastroenterology and Russian association of coloproctology on diagnostics and treatment of ulcerative colitis. Koloproktologia. 2017;1:6-30 (In Russ.)].
3. Khor B, Gardet A, Xavier RJ. Genetics and pathogenesis of inflammatory bowel disease. Nature. 2011;474(7351):307-17. doi: 10.1038/nature10209
4. Jostins L, Ripke S, Weersma RK, et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature. 2012;491(7422):119-24. doi: 10.1038/nature11582
5. McGonagle D, McDermott MF. A proposed classification of the immunological diseases. PLoS Med. 2006;3(8):e297. doi: 10.1371/journal.pmed.0030297
6. Kayama H, Takeda K. Functions of innate immune cells and commensal bacteria in gut homeostasis. J Biochem. 2016;159(2):141-9. doi: 10.1093/jb/mvv119
7. Choy MC, Visvanathan K, De Cruz P. An Overview of the innate and adaptive immune system in inflammatory bowel disease. Inflamm Bowel Dis. 2017;23(1):2-13. doi: 10.1097/MIB.0000000000000955
8. Norouzinia M, Chaleshi V, Alizadeh AHM, Zali MR. Biomarkers in inflammatory bowel diseases: insight into diagnosis, prognosis and treatment. Gastroenterol Hepatol Bed Bench. 2017;10(3):155-167
9. Mitsuyama K, Niwa M, Takedatsu H, et al. Antibody markers in the diagnosis of inflammatory bowel disease. World J Gastroenterol. 2016;22(3):1304-10. doi: 10.3748/wjg.v22.i3.1304
10. Bossuyt X. Serologic markers in inflammatory bowel disease. Clin Chem. 2006;52(2):171-81. doi: 10.1373/clinchem.2005.058560
11. Dotan I. New serologic markers for inflammatory bowel disease diagnosis. Dig Dis. 2010;28(3):418-23. doi: 10.1159/000320396
12. Kuna AT. Serological markers of inflammatory bowel disease. Biochem Med (Zagreb). 2013;23(1):28-42. doi: 10.11613/bm.2013.006
13. Kovács M, Müller KE, Papp M, et al. New serological markers in pediatric patients with inflammatory bowel disease. World J Gastroenterol. 2014;20(17):4873-82. doi: 10.3748/wjg.v20.i17.4873
14. Arai R. Serologic markers: impact on early diagnosis and disease stratification in inflammatory bowel disease. Postgrad Med. 2010;122(4):177-85. doi: 10.3810/pgm.2010.07.2184
15. Prideaux L, De Cruz P, Ng SC, Kamm MA. Serological antibodies in inflammatory bowel disease: a systematic review. Inflamm Bowel Dis. 2012;18(7):1340-55. doi: 10.1002/ibd.21903
16. Bonneau J, Dumestre-Perard C, Rinaudo-Gaujous M, et al. Systematic review: new serological markers (anti-glycan, anti-GP2, anti-GM-CSF Ab) in the prediction of IBD patient outcomes. Autoimmun Rev. 2015;14(3):231-45. doi: 10.1016/j.autrev.2014.11.004
17. Peyrin-Biroulet L, Standaert-Vitse A, Branche J, Chamaillard M. IBD serological panels: facts and perspectives. Inflamm Bowel Dis. 2007;13(12):1561-6. doi: 10.1002/ibd.20226
18. Mukhtyar C, Flossmann O, Hellmich B, et al. Outcomes from studies of antineutrophil cytoplasm antibody associated vasculitis: a systematic review by the European League Against Rheumatism systemic vasculitis task force. Ann Rheum Dis. 2008; 67:1004-10. doi: 10.1136/ard.2007.071936
19. Desplat-Jégo S, Johanet C, Escande A, et al. Update on Anti-Saccharomyces cerevisiae antibodies, anti-nuclear associated anti-neutrophil antibodies and antibodies to exocrine pancreas detected by indirect immunofluorescence as biomarkers in chronic inflammatory bowel diseases: results of a multicenter study. World J Gastroenterol. 2007;13(16):2312-8. doi: 10.3748/wjg.v13.i16.2312
20. Conrad K, Roggenbuck D, Laass MW. Diagnosis and classification of ulcerative colitis. Autoimmun Rev. 2014;13(4-5):463-6. doi: 10.1016/j.autrev.2014.01.028
21. Schulte-Pelkum J, Radice A, Norman GL, et al. Novel clinical and diagnostic aspects of antineutrophil cytoplasmic antibodies. J Immunol Res. 2014;2014:185416. doi: 10.1155/2014/185416
22. Joossens S, Vermeire S, Van Steen K, et al. Pancreatic autoantibodies in inflammatory bowel disease. Inflamm Bowel Dis. 2004;10(6):771-7. doi: 10.1097/00054725-200411000-00012
23. Zhou G, Song Y, Yang W, et al. ASCA, ANCA, ALCA and Many More: Are They Useful in the Diagnosis of Inflammatory Bowel Disease? Dig Dis. 2016;34(1-2):90-7. doi: 10.1159/000442934
24. Laass MW, Roggenbuck D, Conrad K. Diagnosis and classification of Crohn’s disease. Autoimmun Rev. 2014;13(4-5):467-71. doi: 10.1016/j.autrev.2014.01.029
25. Ferrante M, Henckaerts L, Joossens M, et al. New serological markers in inflammatory bowel disease are associated with complicated disease behaviour. Gut. 2007;56(10):1394-403. doi: 10.1136/gut.2006.108043
26. Papp M, Altorjay I, Dotan N, et al. New serological markers for inflammatory bowel disease are associated with earlier age at onset, complicated disease behavior, risk for surgery, and NOD2/CARD15 genotype in a Hungarian IBD cohort. Am J Gastroenterol. 2008;103:665-81. doi: 10.1111/j.1572-0241.2007.01652.x
27. Seow CH, Stempak JM, Xu W, et al. Novel anti-glycan antibodies related to inflammatory bowel disease diagnosis and phenotype. Am J Gastroenterol. 2009;104:1426-34. doi: 10.1038/ajg.2009.79
28. Markowitz J, Kugathasan S, Dubinsky M, et al. Age of diagnosis influences serologic responses in children with Crohn’s disease: a possible clue to etiology? Inflamm Bowel Dis. 2009;15:714-9. doi: 10.1002/ibd.20831
29. Rieder F, Schleder S, Wolf A, et al. Serum anti-glycan antibodies predict complicated Crohn’s disease beh * avior: a cohort study. Inflamm Bowel Dis. 2010;16(8):1367-75. doi: 10.1002/ibd.21179
30. Somma V, Ababneh H, Ababneh A, et al. The novel Crohn’s disease marker anti-GP2 antibody is associated with ileocolonic location of disease. Gastroenterol Res Pract. 2013;2013:1-7. doi: 10.1155/2013/683824
31. Däbritz J, Bonkowski E, Chalk C, et al. Granulocyte macrophage colony-stimulating factor auto-antibodies and disease relapse in inflammatory bowel disease. Am J Gastroenterol. 2013;108:1901-10. doi: 10.1038/ajg.2013.360
32. Mokrowiecka A, Kumor A, Jakubczyk E, et al. The application of Montreal classification in different clinical and serological IBD subtypes. Hepatogastroenterology. 2010;57(101):787-93
33. Targan SR, Landers CJ, Yang H, et al. Antibodies to CBir1 flagellin define a unique response that is associated independently with complicated Crohn’s disease. Gastroenterology. 2005;128(7):2020-8. doi: 10.1053/j.gastro.2005.03.046
34. Mow WS, Vasiliauskas EA, Lin YC, et al. Association of antibody responses to microbial antigens and complications of small bowel Crohn’s disease. Gastroenterology. 2004;126(2):414-24. doi: 10.1053/j.gastro.2003.11.015
35. Esters N, Vermeire S, Joossens S, et al. Serological markers for prediction of response to anti-tumor necrosis factor treatment in Crohn’s disease. Am J Gastroenterol. 2002; 97:1458-62. doi: 10.1111/j.1572-0241.2002.05689.x
36. Ferrante M, Vermeire S, Katsanos KH, et al. Predictors of early response to infliximab in patients with ulcerative colitis. Inflamm Bowel Dis. 2007;13:123-8. doi: 10.1002/ibd.20054
37. Israeli E, Grotto I, Gilburd B, et al. Anti-Saccharomyces cerevisiae and antineutrophil cytoplasmic antibodies as predictors of inflammatory bowel disease. Gut. 2005;54:1232-6. doi: 10.1136/gut.2004.060228

________________________________________________

1. Клинические рекомендации по диагностике и лечению болезни Крона у взрослых (проект). Колопроктология. 2020;19(2):8-38 [Crohn’s disease. Clinical recommendations (preliminary version). Koloproktologia. 2020;19(2):8-38 (In Russ.)]. doi: 10.33878/2073-7556-2020-19-2-8-38
2. Ивашкин В.Т., Шелыгин Ю.А., Халиф И.Л. и др. Клинические рекомендации Российской гастроэнтерологической ассоциации и Ассоциации колопроктологов России по диагностике и лечению язвенного колита. Колопроктология. 2017;1:6-30 [Ivashkin VT, Shelygin IuA, Khalif IL, et al. Clinical guide of Russian association of gastroenterology and Russian association of coloproctology on diagnostics and treatment of ulcerative colitis. Koloproktologia. 2017;1:6-30 (In Russ.)].
3. Khor B, Gardet A, Xavier RJ. Genetics and pathogenesis of inflammatory bowel disease. Nature. 2011;474(7351):307-17. doi: 10.1038/nature10209
4. Jostins L, Ripke S, Weersma RK, et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature. 2012;491(7422):119-24. doi: 10.1038/nature11582
5. McGonagle D, McDermott MF. A proposed classification of the immunological diseases. PLoS Med. 2006;3(8):e297. doi: 10.1371/journal.pmed.0030297
6. Kayama H, Takeda K. Functions of innate immune cells and commensal bacteria in gut homeostasis. J Biochem. 2016;159(2):141-9. doi: 10.1093/jb/mvv119
7. Choy MC, Visvanathan K, De Cruz P. An Overview of the innate and adaptive immune system in inflammatory bowel disease. Inflamm Bowel Dis. 2017;23(1):2-13. doi: 10.1097/MIB.0000000000000955
8. Norouzinia M, Chaleshi V, Alizadeh AHM, Zali MR. Biomarkers in inflammatory bowel diseases: insight into diagnosis, prognosis and treatment. Gastroenterol Hepatol Bed Bench. 2017;10(3):155-167
9. Mitsuyama K, Niwa M, Takedatsu H, et al. Antibody markers in the diagnosis of inflammatory bowel disease. World J Gastroenterol. 2016;22(3):1304-10. doi:
10.3748/wjg.v22.i3.1304
10. Bossuyt X. Serologic markers in inflammatory bowel disease. Clin Chem. 2006;52(2):171-81. doi: 10.1373/clinchem.2005.058560
11. Dotan I. New serologic markers for inflammatory bowel disease diagnosis. Dig Dis. 2010;28(3):418-23. doi: 10.1159/000320396
12. Kuna AT. Serological markers of inflammatory bowel disease. Biochem Med (Zagreb). 2013;23(1):28-42. doi: 10.11613/bm.2013.006
13. Kovács M, Müller KE, Papp M, et al. New serological markers in pediatric patients with inflammatory bowel disease. World J Gastroenterol. 2014;20(17):4873-82. doi: 10.3748/wjg.v20.i17.4873
14. Arai R. Serologic markers: impact on early diagnosis and disease stratification in inflammatory bowel disease. Postgrad Med. 2010;122(4):177-85. doi:
10.3810/pgm.2010.07.2184
15. Prideaux L, De Cruz P, Ng SC, Kamm MA. Serological antibodies in inflammatory bowel disease: a systematic review. Inflamm Bowel Dis. 2012;18(7):1340-55. doi: 10.1002/ibd.21903
16. Bonneau J, Dumestre-Perard C, Rinaudo-Gaujous M, et al. Systematic review: new serological markers (anti-glycan, anti-GP2, anti-GM-CSF Ab) in the prediction of IBD patient outcomes. Autoimmun Rev. 2015;14(3):231-45. doi: 10.1016/j.autrev.2014.11.004
17. Peyrin-Biroulet L, Standaert-Vitse A, Branche J, Chamaillard M. IBD serological panels: facts and perspectives. Inflamm Bowel Dis. 2007;13(12):1561-6. doi: 10.1002/ibd.20226
18. Mukhtyar C, Flossmann O, Hellmich B, et al. Outcomes from studies of antineutrophil cytoplasm antibody associated vasculitis: a systematic review by the European League Against Rheumatism systemic vasculitis task force. Ann Rheum Dis. 2008; 67:1004-10. doi: 10.1136/ard.2007.071936
19. Desplat-Jégo S, Johanet C, Escande A, et al. Update on Anti-Saccharomyces cerevisiae antibodies, anti-nuclear associated anti-neutrophil antibodies and antibodies to exocrine pancreas detected by indirect immunofluorescence as biomarkers in chronic inflammatory bowel diseases: results of a multicenter study. World J Gastroenterol. 2007;13(16):2312-8. doi: 10.3748/wjg.v13.i16.2312
20. Conrad K, Roggenbuck D, Laass MW. Diagnosis and classification of ulcerative colitis. Autoimmun Rev. 2014;13(4-5):463-6. doi: 10.1016/j.autrev.2014.01.028
21. Schulte-Pelkum J, Radice A, Norman GL, et al. Novel clinical and diagnostic aspects of antineutrophil cytoplasmic antibodies. J Immunol Res. 2014;2014:185416. doi: 10.1155/2014/185416
22. Joossens S, Vermeire S, Van Steen K, et al. Pancreatic autoantibodies in inflammatory bowel disease. Inflamm Bowel Dis. 2004;10(6):771-7. doi: 10.1097/00054725-200411000-00012
23. Zhou G, Song Y, Yang W, et al. ASCA, ANCA, ALCA and Many More: Are They Useful in the Diagnosis of Inflammatory Bowel Disease? Dig Dis. 2016;34(1-2):90-7. doi: 10.1159/000442934
24. Laass MW, Roggenbuck D, Conrad K. Diagnosis and classification of Crohn’s disease. Autoimmun Rev. 2014;13(4-5):467-71. doi: 10.1016/j.autrev.2014.01.029
25. Ferrante M, Henckaerts L, Joossens M, et al. New serological markers in inflammatory bowel disease are associated with complicated disease behaviour. Gut. 2007;56(10):1394-403. doi: 10.1136/gut.2006.108043
26. Papp M, Altorjay I, Dotan N, et al. New serological markers for inflammatory bowel disease are associated with earlier age at onset, complicated disease behavior, risk for surgery, and NOD2/CARD15 genotype in a Hungarian IBD cohort. Am J Gastroenterol. 2008;103:665-81. doi: 10.1111/j.1572-0241.2007.01652.x
27. Seow CH, Stempak JM, Xu W, et al. Novel anti-glycan antibodies related to inflammatory bowel disease diagnosis and phenotype. Am J Gastroenterol. 2009;104:1426-34. doi: 10.1038/ajg.2009.79
28. Markowitz J, Kugathasan S, Dubinsky M, et al. Age of diagnosis influences serologic responses in children with Crohn’s disease: a possible clue to etiology? Inflamm Bowel Dis. 2009;15:714-9. doi: 10.1002/ibd.20831
29. Rieder F, Schleder S, Wolf A, et al. Serum anti-glycan antibodies predict complicated Crohn’s disease beh * avior: a cohort study. Inflamm Bowel Dis. 2010;16(8):1367-75. doi: 10.1002/ibd.21179
30. Somma V, Ababneh H, Ababneh A, et al. The novel Crohn’s disease marker anti-GP2 antibody is associated with ileocolonic location of disease. Gastroenterol Res Pract. 2013;2013:1-7. doi: 10.1155/2013/683824
31. Däbritz J, Bonkowski E, Chalk C, et al. Granulocyte macrophage colony-stimulating factor auto-antibodies and disease relapse in inflammatory bowel disease. Am J Gastroenterol. 2013;108:1901-10. doi: 10.1038/ajg.2013.360
32. Mokrowiecka A, Kumor A, Jakubczyk E, et al. The application of Montreal classification in different clinical and serological IBD subtypes. Hepatogastroenterology. 2010;57(101):787-93
33. Targan SR, Landers CJ, Yang H, et al. Antibodies to CBir1 flagellin define a unique response that is associated independently with complicated Crohn’s disease. Gastroenterology. 2005;128(7):2020-8. doi: 10.1053/j.gastro.2005.03.046
34. Mow WS, Vasiliauskas EA, Lin YC, et al. Association of antibody responses to microbial antigens and complications of small bowel Crohn’s disease. Gastroenterology. 2004;126(2):414-24. doi: 10.1053/j.gastro.2003.11.015
35. Esters N, Vermeire S, Joossens S, et al. Serological markers for prediction of response to anti-tumor necrosis factor treatment in Crohn’s disease. Am J Gastroenterol. 2002; 97:1458-62. doi: 10.1111/j.1572-0241.2002.05689.x
36. Ferrante M, Vermeire S, Katsanos KH, et al. Predictors of early response to infliximab in patients with ulcerative colitis. Inflamm Bowel Dis. 2007;13:123-8. doi:
10.1002/ibd.20054
37. Israeli E, Grotto I, Gilburd B, et al. Anti-Saccharomyces cerevisiae and antineutrophil cytoplasmic antibodies as predictors of inflammatory bowel disease. Gut. 2005;54:1232-6. doi: 10.1136/gut.2004.060228

Авторы

Е.Н. Александрова, А.А. Новиков, Г.В. Лукина, А.И. Парфенов

ГБУЗ «Московский клинический научно-практический центр им. А.С. Логинова» Департамента здравоохранения г. Москвы, Москва, Россия

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E.N. Aleksandrova, A.A. Novikov, G.V. Lukina, A.I. Parfenov

Loginov Moscow Clinical Research and Practical Center, Moscow, Russia

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