Clinical and Experimental Pediatrics

대한소아청소년과학회 (The Korean Pediatric Society)
권호 표지
DOI QR코드

DOI QR Code

Helicobacter pylori 감염 소아에서 위점막 면역반응

Gastric mucosal immune response of Helicobacter pylori-infected children

  • 염혜원 (이화여자대학교 의과대학 소아과학교실) ;
  • 서정완 (이화여자대학교 의과대학 소아과학교실)
  • Yom, Hye Won (Department of Pediatrics, Ewha Womans University School of Medicine) ;
  • Seo, Jeong Wan (Department of Pediatrics, Ewha Womans University School of Medicine)
  • 투고 : 2008.02.20
  • 심사 : 2008.03.18
  • 발행 : 2008.05.15
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

목 적 : H. pylori의 감염은 세균의 병독 인자, 숙주 인자, 환경 인자가 복합적으로 작용하여 다양한 위장관 병변을 일으킨다. H. pylori의 병리 기전으로 지금까지는 주로 세균의 병독성에 초점을 맞추었으나 최근에는 숙주의 위점막 면역반응이 주목을 받고 있다. 소아는 술, 담배, 약물과 같은 환경 인자의 영향이 적어 연구에 적합한 대상이며 감염 초기를 반영한다는 측면에서 중요한 의의가 있음에도 불구하고 소아에서 위점막 면역반응에 관한 연구가 거의 없다. 이에 H. pylori 감염 소아에서 위점막 림프구를 분석하여 소아에서 H. pylori 감염으로 인한 국소 면역반응의 특징을 알아보고자 하였다. 방 법 : H. pylori 양성 소화궤양군 10명, H. pylori 양성 위염군 15명, H. pylori 음성 대조군 20명에서 얻은 위전정부 생검조직에서 hematoxylin-eosin 염색과 modified Giemsa 염색을 시행하여 개정된 시드니 체계에 따라 위염의 정도를 점수화하였다. 위점막에서 림프구 면역표현형을 알기 위해 CD3, CD4, CD8 T세포와 CD20 B세포에 대한 면역조직화학염색을 시행하였으며 점막 고유층에서는 400배 고배율 현미경 하에서 $0.0625m^2$ 당 양성 림프구 수를 기록하였고, 상피세포 내에서는 100개 상피세포 당 양성 림프구 수를 기록하였다. 결 과 : 림프구 침윤은 점막 고유층에서 상피세포 내보다 확연히 많았다. 점막 고유층에서 H. pylori 양성군에서 대조군에 비해 CD3, CD4, CD8 T세포와 CD20 B세포가 유의하게 증가하였고(P<0.01) H. pylori 양성 소화궤양군은 위염군과 달리 대조군에 비해 CD8 T세포가 유의하게 증가하였다(P<0.01). 한편, 상피세포 내에서는 H. pylori 양성 소화궤양군과 위염군 모두 대조군에 비해 CD4 T세포가 유의하게 증가하였다(P<0.01). H. pylori의 밀도, 다핵형 중성구의 활동성, 만성 염증 정도와 림프구 수는 점막 고유층에서 상피세포 내보다 더 밀접한 상관관계가 있었다. 결 론: H. pylori에 감염된 소아의 국소 면역반응은 주로 위점막 고유층에서 일어나며 T세포와 B세포가 함께 관여하였다. H. pylori 양성 소화궤양군에서 점막 고유층의 CD8 T세포가 유의하게 증가하여 임상질환과 점막면역의 연관성을 추정할 수 있었다. 향후 H. pylori 감염에서 국소 면역반응으로 야기되는 점막 손상, 연령과 인종에 따른 차이, 임상질환과의 연관성 등에 대하여 더 많은 연구가 이루어져야 할 것이다.

Purpose : Helicobacter pylori infection is one of the most common gastrointestinal infections worldwide; it almost invariably causes chronic gastritis. Pediatric studies may provide important insights into the mucosal immune response of H. pylori-infection, as children are not submitted to environmental factors such as alcohol, tobacco and anti-inflammatory medication. The aim of the present study was to investigate the mucosal immune response against H. pylori in clinically well-defined groups: H. pylori-positive (divided into peptic ulcer disease and gastritis) and H. pylori-negative control. Methods : Antral biopsies were obtained from 45 children undergoing an upper GI endoscopy for dyspeptic symptoms. T cells (CD3+, CD4+, CD8+) and B cells (CD20+) were analyzed by quantitative immunohistochemistry. The correlation of lymphocyte subsets of gastric mucosa with histology was evaluated. Results : T cells (CD3+, CD4+, CD8+) and B cells (CD20+) were significantly increased in the lamina propria of H. pylori-positive group (P<0.01). CD8+ T cells were significantly increased in the lamina propria of the H. pylori-positive peptic ulcer disease (P<0.01). Within the epithelium, only CD4+ T cells were significantly increased in the H. pylori-positive group (P<0.01). Gastric histological parameters had a closer correlation with lymphocytes in the lamina propria than intraepithelial lymphocytes. Conclusion : This study suggests that both T cells and B cells in the lamina propria play important roles in the local immune response of H. pylori-infected children. Furthermore, it remains to be elucidated whether CD8+ T cells in the lamina propria may contribute to peptic ulcer formation in H. pylori-infected children.

키워드

참고문헌

  1. Ernst PB, Gold BD. The disease spectrum of Helicobacter pylori: the irnrmmopathog enesis of gastroduodenal ulcer and gastric cancer. Annu Rev Microbiol 2000 54:615-40. https://doi.org/10.1146/annurev.micro.54.1.615
  2. Drurnrn B, Day AS, Gold B, Gottrand F, Kato S, Kawakami E, et al. Helicobacter pylori and peptic ulcer: Working Group Report of the second World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr 2004;39 Suppl 2:S626-31. https://doi.org/10.1097/00005176-200406002-00008
  3. Seo JW, Han WS. Histologic study of Helicobacter pylori¬associated gastritis in children. J Korean Pediatrics Soc 1996;39:811-20.
  4. Graham DY, Yamaoka Y. Disease-epecific Helicobacter pylori virulence factors: the unfulfilled promise. Helicobacter 2000;5 Suppl 1:S3-9. https://doi.org/10.1046/j.1523-5378.2000.0050S1003.x
  5. Jung JA, Lee MA, Seo JW. The genotypes of Helicobacter pylori, gastric epithelial cell proliferation and apoptosis in children. Korean J Pediatr Gastroenterol Nutr 2003;6:1-9.
  6. Munzenmaier A, Lange C, Glocker E, Covacci A, Moran A, Bereswill S, et al. A secreted/shed product of Helicobacter pylori activates transcription factor nuclear factor-kappa B. J Immunol 1997;159:6140-7.
  7. Bodger K, Crabtree JE. Helicobacter pylori and gastric inflammation. Br Med Bull 1998 54:139-50. https://doi.org/10.1093/oxfordjournals.bmb.a011664
  8. Fan XJ. Chua A, Sham CN, McDevitt J. Keeling PW, Kelleher D. Gastric T lymphocyte responses to Helicobacter pylori in patients with H pylori colonization. Gut 1994; 35:1879-84.
  9. Agnihotri N, Bhasin DK, Vohra H, Ray P, Singh K, Ganguly NK. Characterization of lymphocytic subsets and cytokine production in gastric biopsy samples from Helicobacter pylori patients. Scand J Gastroenterol 1998;33:704-9. https://doi.org/10.1080/00365529850171639
  10. Hatz RA, Meimarakis G, Bayerdorffer E, Stolte M, Kirchner T, Enders G. Characterization of lymphocytic infiltrates in Helicobacter pylori-associated gastritis. Scand J Gastroenterol 1996;31:222-8. https://doi.org/10.3109/00365529609004870
  11. Sommer F, Faller G, Konturek P, Kirchner T, Hahn EG, Zeus J, et al. Antrum- and corpus mucosa-infiltrating CD4( +) lymphocytes in Helicobacter pylori gastritis display a Thl phenotype. Infect Immun 1998;66:5543-6.
  12. Bamford KB, Fan X, Crowe SE, Leary JF, Gourley WK, Luthra GK, et al. Lymphocytes in the human gastric mucosa during Helicobacter pylori have a T helper cell 1 phenotype. Gastroenterology 1998;114:482-92. https://doi.org/10.1016/S0016-5085(98)70531-1
  13. Stromberg E, Lundgren A, Edebo A, Lundin S, Svennerhobn AM, Lindhobn C. Increased frequency of activated T-cells in the Helicobacter pylori-infected antrum and duodenum. FEMS lmmunol Med Microbiol 2003;36:159-68. https://doi.org/10.1016/S0928-8244(03)00026-9
  14. Lindholm C, Quiding- Jarhrink M, Lonroth H, Harolet A, Svennerhobn AM. Local cytokine response in Helicobacter pylori-infected subjects. Infect lmmun 1998;66:5964-71.
  15. Lopes AI, Victorino RM, Palha A11, Ruivo J, Fernandes A Mucosal lymphocyte subsets and HLA-DR antigen expression in paediatric Helicobacter pylori-associated gastritis, Clin Exp lmmunol 2006;145:13-20. https://doi.org/10.1111/j.1365-2249.2006.03100.x
  16. Krauss- Etschmann S, Sammler E, Koletzko S, Konstan-topoulos N, Aust D, Gebert B, et al. Chemokine receptor 5 expression in gastric mucosa of Helicobacter pylori-infected and noninfected children, Clin Diagn Lab lmmunol 2003;10:22-9.
  17. Krauss- Etschmann S, Gruber R, Plikat K, Antoni I, Demnucelmair H, Reinhardt D, et al. Increase of antigen-presenting cells in the gastric mucosa of Helicobacter pylori-infected children, Helicobacter 2005;10:214-22. https://doi.org/10.1111/j.1523-5378.2005.00313.x
  18. Labigue.A, Cussac V, Courcoux P, Shuttle cloning and nucleotide sequences of Helicobacter pylori genes responsible for urease activity, J Bacteriol 1991 173:1920-31. https://doi.org/10.1128/jb.173.6.1920-1931.1991
  19. Dixon MF, Genta RM, Yardley JH, Correa P, Classification and grading of gastritis, The updated Sydney System, Am J Surg Pathol 1996:20:1161-81. https://doi.org/10.1097/00000478-199610000-00001
  20. Goll R, Husebekk A, Isaksen V, Kauric G, Hansen T, Florholmen J. Increased frequency of antral CD4 T and CD19 B cells in patients with Helicobacter pylori -related peptic ulcer disease, Scand J lmmunol 2005;61:92-7, https://doi.org/10.1111/j.0300-9475.2005.01537.x
  21. Shi HN, Nagler-Anderson C. Mucosal T-cell responses to enteric infection, Curr Opin Gastroenterol 1999;15:529-33. https://doi.org/10.1097/00001574-199911000-00013
  22. Lundgren A, Trollmo C, Edebo A, Svennerhobn AM, Lundin BS, Helicobacter pylori-specific CD4+ T cells home to and accurnulate in the human Helicobacter pylori-infected gastric mucosa, Infect lmmun 2005;73:5612-9. https://doi.org/10.1128/IAI.73.9.5612-5619.2005
  23. Janeway CA, Traverse P, Walport M, Shlomchik M, Immunobiology. 6th ed. New York: Garland Science, 2005:416-46.
  24. Eaton KA, Mefford M, Thevenot T. The role of T cell subsets and cytokines in the pathogenesis of Helicobacter pylori gastritis in mice, J lmmunol 2001 166:7456-61.
  25. Cacciarelli AG, Marano BJ Jr. Gualtieri NlvI, Zuretti AR, Torres RA, Starpoli AA, et al. Lower Helicobacter pylori infection and peptic ulcer disease prevalence in patients with AIDS and suppressed CD4 counts, Am J Gastroenterol 1996:91:1783-4.
  26. Pappo J, Torrey D, Castriotta L, Savinainen A, Kabok Z, Ibraghirnov A Helicobacter pylori infection in immunized mice lacking major histocompatibility complex class I and class II functions, Infect lmmun 1999;67:337-41.
  27. Lundgren A, Suri-Payer E, Enarsson K, Svennerholm AM, Lundin BS, Helicobacter pylori-specific CD4+ CD25high re¬gulatory T cells suppress memory T-cell responses to H pylori in infected individuals, Infect lmmun 2003;71:1755-62, https://doi.org/10.1128/IAI.71.4.1755-1762.2003
  28. Nurgalieva ZZ, Conner ME, Opekun AR, Zheng CQ, Elliott SN, Ernst PB, et al. B-cell and T-cell immune responses to experimental Helicobacter pylori infection in humans, Infect lmmun 2005:73:2999-3006. https://doi.org/10.1128/IAI.73.5.2999-3006.2005
  29. Bontems P, Robert F, Van Gossurn A, Cadranel S, Mascart F. Helicobacter pylori modulation of gastric and duodenal mucosal T cell cytokine secretions in children compared with adults, Helicobacter 2003;8:216-26. https://doi.org/10.1046/j.1523-5378.2003.00147.x
  30. Quiding- Jarbrink M, Lundin BS, Lonroth H, Svennerhobn AM, CD4+ and CD8+ T cell responses in Helicobacter pylori-infected individuals, Clin Exp Immunol 2001;123:81-7. https://doi.org/10.1046/j.1365-2249.2001.01427.x
  31. Ohara T, Morishita T, Suzuki H, Masaoka T, Ishii H Perforin and granzyrne B of cytotoxic T lymphocyte mediate apoptosis irrespective of Helicobacter pylori infection: possible act as a trigger of peptic ulcer formation, Hepatogastroenterology 2003:50:1774-9.
  32. Bedoya A, Garay J, Sanzon F, Bravo LE, Bravo JC, Correa H, et al. Histopathology of gastritis in Helicobacter pylori-infected children from populations at high and low gastric cancer risk. Hum Pathol 2003;34:206-13. https://doi.org/10.1053/hupa.2003.43
  33. Wang LL, Shan QW, Jiang HX, Tran DB, Qin X, Xie XZ, et al. Detection of T lymphocyte subsets of children with Helicobacter pylori infection, World J Gastroenterol 2005; 11:2827-9. https://doi.org/10.3748/wjg.v11.i18.2827
  34. Soares TF, Rocha GA, Rocha AM, Correa-Oliveira R, Martins-Filho OA, Carvalho AS, et al. Phenotypic study of peripheral blood lymphocytes and humoral immune response in Helicobacter pylori infection according to age, Scand J Immunol 2005:62:63-70. https://doi.org/10.1111/j.1365-3083.2005.01638.x
  35. Schmucker DL, Owen RL, Outenreath R, Thoreux K Basis for the age-related decline in intestinal mucosal immunity, Clin Dev lmmunol 2003:10:167-72. https://doi.org/10.1080/10446670310001642168
  36. Andersen LP, Holck S, janulaityte-Gunther D, Kupcinskas L, Kiudelis G, jonaitis L, et al. Gastric inflammatory markers and interleukins in patients with functional dyspepsia, with and without Helicobacter pylori infection, FEMS lmmunol Med Microbiol 2005:44:233-8. https://doi.org/10.1016/j.femsim.2004.10.022
  37. Camorlinga-Ponce M, Aviles-Jimenez F, Cabrera L, Hernandez-Pando R, Munoz O, Soza J, et al. Intensity of inflammation, density of colonization and interleukin-B response in the gastric mucosa of children infected with Helicobacter pylori, Helicobacter 2003;8:554-60. https://doi.org/10.1046/j.1523-5378.2003.00176.x