| Peer-Reviewed

The Significance of Fas/Fasl Expression in Celiac Disease, Non-Specific Duedonitis and in Duedonum Biopsies Showing Increase in Intraepithelial Lymphocytes

Received: 26 September 2014     Accepted: 9 October 2014     Published: 20 October 2014
Views:       Downloads:
Abstract

Aim: Celiac disease (CD) is a chronic malabsorbtion disease of the small bowel. With a prevelance of about %1 it is a common disease in the community. FAS-FASL system which induces apopitosis is one of the most important pathways and responsible fort he development of mucosal atrophy in CD. The aim of this study is to investigate the patients who has the increase of intraepithelial lymphocytes (İEL) in duedonal mucosa and non specific duedonitis (NSD) and significance of FAS-FASL expression in these patients to distinct from CD.Materials and methods: 29 adults and 7 children celiac patients (with a preliminary diagnosis as iron deficiency anemia) and 17 adults and 6 children non-specific duedonitis patients included in the study. CD3, CD8, FAS and FASL expression were examined immunohistochemically from sections prepared from paraffin blocks in 28 adults and 7 children with normal duedonal mucosa and 24 adults and 6 children who has the increase of İEL in duedonum.Results: İn all groups; the number of İEL seen much more with CD3 in HE (hematoxylin eosin) sections . Again in all groups it is determined that majority of İEL expresses CD3 and CD8. Both in adult and children group; in surface and crypt enterosits in İEL ; the highest FAS expression was seen in enterosits and lamina propria cells in CD .More expression was determined in patients with the group who has İEL in duedonum and with NSD when compared to control group. FASL expression is increased in CD in comparison with normal but it was low in the group who has İEL in duedonum and NSD group. We found that FAS-FASL expression is not only an effective mechanism in pathogenesis of CD. We suggest that the functional significance of FAS expression should be investigated by methods of evaluating apopitosis in patients with İELAG and NSD who has more FAS expression when compared to CD . Also in the detection of number of İEL in suspected cases routine use of CD3 immunohistochemical evaluation may be useful.

Published in American Journal of Clinical and Experimental Medicine (Volume 2, Issue 5)
DOI 10.11648/j.ajcem.20140205.14
Page(s) 106-116
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2014. Published by Science Publishing Group

Keywords

Celiac Disease (CD), İncreased İntraepithelial Lymphocytes (İEL),Non-Spesific Duedonitis(NSD), FAS, FASL

References
[1] Cecilia M, Fenoglio-Preiser. The Nonneoplastic Small Intestine In: Gastrointestinal Pathology : An Atlas and Text, Lippincott Williams and Wilkins 4th edt, 2008,p275-470.
[2] van Heel DA, West J. Recent Advances In Coeliac Disease, Gut 2006;55:1037-1046.
[3] Freeman HJ. Lymphoproliferative and intestinal malignancies in 214 patients with biopsy-defined celiac disease, J Clin Gastroenterol. 2004;38(5):429-34.
[4] Robert ME. Gluten sensitive enteropathy and other causes of small intestinal lymphocytosis, Semin Diagn Pathol. 2005;22(4):284-94.
[5] Herr I, Debatin KM. Cellular stress response and apoptosis in cancer therapy, Blood. 2001;98(9):2603-14.
[6] Watson AJ. Necrosis and apoptosis in the gastrointestinal tract, Gut. 1995;37(2):165-7.
[7] Ciccocippo R, Di Sabatino A, Parroni R, D'alò S, Pistoia MA, Doglioni C, Cifone MG, Corazza GR. Cytolitic mechanisms of intraepithelial lymphocytes in coeliac disease(CoD), Clin Exp Immunol. 2000;120(2):235-40.
[8] Moss SF, Attia L, Scholes JV, Walters JR, Holt PR. Increased small intestinal apoptosis in coeliac disease, Gut. 1996;39(6):811-7.
[9] Pinkoski MJ, Brunner T, Green DR, Lin T. Fas and Fas ligand in gut and liver, Am J Physiol Gastrointest Liver Physiol. 2000;278(3):G354-66
[10] Ciccocioppo R, Di Sabatino A, Parroni R, Muzi P, D'Alò S, Ventura T, Pistoia MA,Cifone MG, Corazza GR. Increased enterocyte apoptosis and Fas-Fas ligand system in celiac disease, Am J Clin Pathol. 2001;115(4):494-503.
[11] Maiuri L, Ciacci C, Raia V, Vacca L, Ricciardelli I, Raimondi F, Auricchio S,Quaratino S, Londei M. FAS engagement drives apoptosis of enterocytes of celiac patients, Gut. 2001;48(3):418-24.
[12] Ciccocioppo R, D’Alo S, Di Sabatino A, Parroni R, Rossi M, Doglioni C, Cifone MG,Corazza GR. Mechanisms of villous atrophy in autoimmune enteropathy and celiac disease, Clin Exp Immunol. 2002;128(1):88-93.
[13] Merger M, Viney JL, Borojevic R, Steele-Norwood D, Zhou P, Clark DA, Riddell R,Maric R, Podack ER, Croitoru K. Defining the roles of perforin, Fas/FasL, and tumour necrosis factor alpha in T cell induced mucosal damage in the mouse intestine, Gut.2002;51(2):155-63.
[14] Ueyama H, Kiyohara T, Sawada N, et al. High Fas ligand expression on lymphocytes in lesions of ulcerative colitis, Gut. 1998;43(1):48-55.
[15] Iwamoto M, Koji T, Makiyama K, Kobayashi N, Nakane PK. Apoptosis of crypt epithelial cells in ulcerative colitis, J Pathol. 1996;180(2):152-9.
[16] Ishihara S, Fukuda R, Kawashima K, et al. T cell-mediated cytotoxicity via Fas/Fas ligand signaling in Helicobacter pylori-infected gastric corpus, Helicobacter.2001;6(4):283-93
[17] Rudi J, Kuck D, Strand S, von Herbay A, Mariani SM, Krammer PH, Galle PR,Stremmel W. Involvement of the CD95(APO-1/Fas) receptor and ligand system in Helicobacter pylori-induced gastric epithelial apoptosis, J Clin Invest. 1998;102(8):1506-14.
[18] Kotlowska-Kmiec A, Bakowska A, Szarszewski A, et al. Helicobacter pylori increases expression of proapoptotic markers Fas and FasL on CD4 lymphocytes in children, Acta Biochim Pol. 2009; 56(3) : 433-8.
[19] Moss SF, Attia L, Scholes JV, Walters JR, Holt PR. Increased small intestinal apoptosis in celiac disease, Gut. 1996;39(6):811-7.
[20] Ciccocippo R, Di Sabatino A, Parroni R, D'alò S, Pistoia MA, Doglioni C, Cifone MG, Corazza GR. Cytolitic mechanisms of intraepithelial lymphocytes in celiac disease (CoD), Clin Exp Immunol. 2000;120(2):235-40.
[21] Mino M, Lauwers GY. Role of lymphocytic immunophenotyping in the diagnosis of gluten-sensitive enteropathy with preserved villous architecture, Am J Surg Pathol.2003;27(9):1237-42.
[22] Salmela MT, MacDonald TT, Black D, Irvine B, Zhuma T, Saarialho-Kere U,Pender SL. Upregulation of matrix metalloproteinases in a model of T cell mediated tissue injury in the gut: analysis by gene array and in situ hybridisation, Gut. 2002;51(4):540-7.
[23] Nagata S. Apoptosis by death factor. Cell. 1997 Feb 7;88(3):355-65.
[24] Ehrmann J Jr, Kolek A, Kod'ousek R, Zapletalová J, Lísová S, Murray PG, Drábek J,Kolár Z. Immunohistochemical study of the apoptotic mechanisms in the intestinal mucosa during children's coeliac disease, Virchows Arch. 2003;442(5):453-61.
[25] Biagi F, Luinetti O, Campanella J, Klersy C, Zambelli C, Villanacci V, Lanzini A,Corazza GR. Intraepithelial lymphocytes in the villous tip: do they indicate potential celiac disease?, J Clin Pathol. 2004;57(8):835-9.
[26] Mino M, Lauwers GY. Role of lymphocytic immunophenotyping in the diagnosis of gluten-sensitive enteropathy with preserved villous architecture, Am J Surg Pathol.2003;27(9):1237-42.
[27] Oberhuber G, Vogelsang H, Stolte M, Muthenthaler S, Kummer JA, Radaszkiewicz.Evidence that intestinal intraepithelial lymphocytes are activated cytotoxic T cells in celiac disease but not in giardiasis, Am J Pathol. 1996;148(5):1351-7.
[28] Verkasalo MA, Arató A, Savilahti E, Tainio VM. Effect of diet and age on jejunal and circulating lymphocyte subsets in children with coeliac disease: persistence of CD4-8-intraepithelial T cells through treatment, Gut. 1990;31(4):422-5.
[29] Jenkins D, Goodall A, Scott BB. T-lymphocyte populations in normal and celiac small intestinal mucosa defined by monoclonal antibodies, Gut. 1986;27(11):1330-7.
[30] Selby WS, Janossy G, Bofill M, Jewell DP. Lymphocyte subpopulations in the human small intestine. The findings in normal mucosa and in the mucosa of patients with adult coeliac disease, Clin Exp Immunol. 1983;52(1):219-28.
[31] Memeo L, Jhang J, Hibshoosh H, Green PH, Rotterdam H, Bhagat G. Duodenal intraepithelial lymphocytosis with normal villous architecture: common occurrence in H.pylori gastritis, Mod Pathol. 2005;18(8):1134-44.
[32] Hasan M, Hay F, Sircus W, Ferguson A. Nature of the inflammatory cell infiltrate in duodenitis, J Clin Pathol. 1983;36(3):280-8.
[33] Oehm A, Behrmann I, Falk W, Pawlita M, Maier G, Klas C, Li-Weber M, Richards S, Dhein J, Trauth BC, et al. Purification and molecular cloning of the APO-1 cell surface antigen, a member of the tumor necrosis factor/nerve growth factor receptor superfamily.Sequence identity with the Fas antigen, J Biol Chem. 1992;267(15):10709-15.
[34] Leithäuser F, Dhein J, Mechtersheimer G, Koretz K, Brüderlein S, Henne C, Schmidt A, Debatin KM, Krammer PH, Möller P. Constitutive and induced expression of APO-1, a new member of the nerve growth factor/tumor necrosis factor receptor superfamily, in normal and neoplastic cells, Lab Invest. 1993;69(4):415-29.
[35] Sträter J, Möller P. Expression and function of death receptors and their natural ligands in the intestine, Ann N Y Acad Sci. 2000;915:162-70
[36] Di Sabatino A, D'Alò S, Millimaggi D, Ciccocioppo R, Parroni R, Sciarra G, Cifone MG, Corazza GR. Apoptosis and peripheral blood lymphocyte depletion in celiac disease, Immunology. 2001;103(4):435-40
[37] Hongo T, Morimoto Y, Iwagaki H, Kobashi K, Yoshii M, Urushihara N, Hizuta A,Tanaka N. Functional expression of Fas and Fas ligand on human colonic intraepithelial T lymphocytes, J Int Med Res. 2000;28(3):132-42.
[38] Wasem C, Frutschi C, Arnold D, Vallan C, Lin T, Green DR, Mueller C, Brunner T.Accumulation and activation-induced release of preformed Fas (CD95) ligand during the pathogenesis of experimental graft-versus-host disease, J Immunol. 2001;167(5):2936-41.
[39] Sakai T, Kimura Y, Inagaki-Ohara K, Kusugami K, Lynch DH, Yoshikai Y. Fasmediated cytotoxicity by intestinal intraepithelial lymphocytes during acute graft-versus host disease in mice, Gastroenterology. 1997;113(1):168-74.
[40] Wasem C, Frutschi C, Arnold D, Vallan C, Lin T, Green DR, Mueller C, Brunner T.Accumulation and activation-induced release of preformed Fas (CD95) ligand during the pathogenesis of experimental graft-versus-host disease, J Immunol. 2001;167(5):2936-41.
[41] Braun MY, Lowin B, French L, Acha-Orbea H, Tschopp J. Cytotoxic T cells deficient in both functional fas ligand and perforin show residual cytolytic activity yet lose their capacity to induce lethal acute graft-versus-host disease, J Exp Med.1996;183(2):657-61
[42] Gargala G, Lecleire S, François A, Jacquot S, Déchelotte P, Ballet JJ, Favennec L,Ducrotté P. Duodenal intraepithelial T lymphocytes in patients with functional dyspepsia,World J Gastroenterol. 2007;13(16):2333-8.
[43] Timmer T, de Vries EG, de Jong S. Fas receptor-mediated apoptosis: a clinical application?, J Pathol. 2002;196(2):125-34.
[44] Sträter J, Möller P. CD95 (Fas/APO-1)/CD95L in the gastrointestinal tract: fictions and facts, Virchows Arch. 2003;442(3):218-25.
[45] Bennett MW, O'Connell J, Houston A, Kelly J, O'Sullivan GC, Collins JK, Shanahan F. Fas ligand upregulation is an early event in colonic carcinogenesis, J Clin Pathol.2001;54(8):598-604.
[46] Giordano C, Stassi G, De Maria R, Todaro M, Richiusa P, Papoff G, Ruberti G,Bagnasco M, Testi R, Galluzzo A. Potential involvement of Fas and its ligand in the pathogenesis of Hashimoto's thyroiditis, Science. 1997;275(5302):960-3.
[47] Melgar S, Bas A, Hammarström S, Hammarström M. Human small intestinal mucosa harbours a small population of cytolytically active CD8+ alphabeta T lymphocytes, Immunology.2002;106(4):476-85.
[48] Souza HS, Neves MS, Elia CC, Tortori CJ, Dines I, Martinusso CA, Madi K,Andrade L, Castelo-Branco MT. Distinct patterns of mucosal apoptosis in H pyloriassociated gastric ulcer are associated with altered FasL and perforin cytotoxic pathways,World J Gastroenterol. 2006;12(38):6133-41.
[49] Ishihara S, Fukuda R, Kawashima K, Moriyama N, Suetsugu H, Ishimura N,Kazumori H, Kaji T, Sato H, Okuyama T, Rumi KM, Adachi K, Watanabe M, Kinoshita Y. T cell-mediated cytotoxicity via Fas/Fas ligand signaling in Helicobacter pyloriinfected gastric corpus, Helicobacter. 2001;6(4):283-93.
[50] Ibuki N, Yamamoto K, Yabushita K, Okano N, Okamoto R, Shimada N, Hakoda T,Mizuno M, Higashi T, Tsuji T. In situ expression of Granzyme B and Fas-ligand in the liver of viral hepatitis, Liver. 2002;22(3):198-204.
Cite This Article
  • APA Style

    Nurdan Tatar, Serdar Yanık, Ayse Neslin Akkoca, Zeynep Tugba Ozdemir, Mustafa Calıskan, et al. (2014). The Significance of Fas/Fasl Expression in Celiac Disease, Non-Specific Duedonitis and in Duedonum Biopsies Showing Increase in Intraepithelial Lymphocytes. American Journal of Clinical and Experimental Medicine, 2(5), 106-116. https://doi.org/10.11648/j.ajcem.20140205.14

    Copy | Download

    ACS Style

    Nurdan Tatar; Serdar Yanık; Ayse Neslin Akkoca; Zeynep Tugba Ozdemir; Mustafa Calıskan, et al. The Significance of Fas/Fasl Expression in Celiac Disease, Non-Specific Duedonitis and in Duedonum Biopsies Showing Increase in Intraepithelial Lymphocytes. Am. J. Clin. Exp. Med. 2014, 2(5), 106-116. doi: 10.11648/j.ajcem.20140205.14

    Copy | Download

    AMA Style

    Nurdan Tatar, Serdar Yanık, Ayse Neslin Akkoca, Zeynep Tugba Ozdemir, Mustafa Calıskan, et al. The Significance of Fas/Fasl Expression in Celiac Disease, Non-Specific Duedonitis and in Duedonum Biopsies Showing Increase in Intraepithelial Lymphocytes. Am J Clin Exp Med. 2014;2(5):106-116. doi: 10.11648/j.ajcem.20140205.14

    Copy | Download

  • @article{10.11648/j.ajcem.20140205.14,
      author = {Nurdan Tatar and Serdar Yanık and Ayse Neslin Akkoca and Zeynep Tugba Ozdemir and Mustafa Calıskan and Didem Sozutek and Pınar Atasoy},
      title = {The Significance of Fas/Fasl Expression in Celiac Disease, Non-Specific Duedonitis and in Duedonum Biopsies Showing Increase in Intraepithelial Lymphocytes},
      journal = {American Journal of Clinical and Experimental Medicine},
      volume = {2},
      number = {5},
      pages = {106-116},
      doi = {10.11648/j.ajcem.20140205.14},
      url = {https://doi.org/10.11648/j.ajcem.20140205.14},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajcem.20140205.14},
      abstract = {Aim: Celiac disease (CD) is a chronic malabsorbtion disease of the small bowel. With a prevelance of about %1 it is a common disease in the community. FAS-FASL system which induces apopitosis is one of the most important pathways and responsible fort he development of mucosal atrophy in CD. The aim of this study is to investigate the patients who has the increase of intraepithelial lymphocytes (İEL) in duedonal mucosa and non specific duedonitis (NSD) and significance of FAS-FASL expression in these patients to distinct from CD.Materials and methods: 29 adults and 7 children celiac patients (with a preliminary diagnosis as iron deficiency anemia) and 17 adults and 6 children non-specific duedonitis patients included in the study. CD3, CD8, FAS and FASL expression were examined immunohistochemically from sections prepared from paraffin blocks in 28 adults and 7 children with normal duedonal mucosa and 24 adults and 6 children who has the increase of İEL in duedonum.Results: İn all groups; the number of İEL seen much more with CD3 in HE (hematoxylin eosin) sections . Again in all groups it is determined that majority of İEL expresses CD3 and CD8. Both in adult and children group; in surface and crypt enterosits in İEL ; the highest FAS expression was seen in enterosits and lamina propria cells in CD .More expression was determined in patients with the group who has İEL in duedonum and with NSD when compared to control group. FASL expression is increased in CD in comparison with normal but it was low in the group who has İEL in duedonum and NSD group. We found that FAS-FASL expression is not only an effective mechanism in pathogenesis of CD. We suggest that the functional significance of FAS expression should be investigated by methods of evaluating apopitosis in patients with İELAG and NSD who has more FAS expression when compared to CD . Also in the detection of number of İEL in suspected cases routine use of CD3 immunohistochemical evaluation may be useful.},
     year = {2014}
    }
    

    Copy | Download

  • TY  - JOUR
    T1  - The Significance of Fas/Fasl Expression in Celiac Disease, Non-Specific Duedonitis and in Duedonum Biopsies Showing Increase in Intraepithelial Lymphocytes
    AU  - Nurdan Tatar
    AU  - Serdar Yanık
    AU  - Ayse Neslin Akkoca
    AU  - Zeynep Tugba Ozdemir
    AU  - Mustafa Calıskan
    AU  - Didem Sozutek
    AU  - Pınar Atasoy
    Y1  - 2014/10/20
    PY  - 2014
    N1  - https://doi.org/10.11648/j.ajcem.20140205.14
    DO  - 10.11648/j.ajcem.20140205.14
    T2  - American Journal of Clinical and Experimental Medicine
    JF  - American Journal of Clinical and Experimental Medicine
    JO  - American Journal of Clinical and Experimental Medicine
    SP  - 106
    EP  - 116
    PB  - Science Publishing Group
    SN  - 2330-8133
    UR  - https://doi.org/10.11648/j.ajcem.20140205.14
    AB  - Aim: Celiac disease (CD) is a chronic malabsorbtion disease of the small bowel. With a prevelance of about %1 it is a common disease in the community. FAS-FASL system which induces apopitosis is one of the most important pathways and responsible fort he development of mucosal atrophy in CD. The aim of this study is to investigate the patients who has the increase of intraepithelial lymphocytes (İEL) in duedonal mucosa and non specific duedonitis (NSD) and significance of FAS-FASL expression in these patients to distinct from CD.Materials and methods: 29 adults and 7 children celiac patients (with a preliminary diagnosis as iron deficiency anemia) and 17 adults and 6 children non-specific duedonitis patients included in the study. CD3, CD8, FAS and FASL expression were examined immunohistochemically from sections prepared from paraffin blocks in 28 adults and 7 children with normal duedonal mucosa and 24 adults and 6 children who has the increase of İEL in duedonum.Results: İn all groups; the number of İEL seen much more with CD3 in HE (hematoxylin eosin) sections . Again in all groups it is determined that majority of İEL expresses CD3 and CD8. Both in adult and children group; in surface and crypt enterosits in İEL ; the highest FAS expression was seen in enterosits and lamina propria cells in CD .More expression was determined in patients with the group who has İEL in duedonum and with NSD when compared to control group. FASL expression is increased in CD in comparison with normal but it was low in the group who has İEL in duedonum and NSD group. We found that FAS-FASL expression is not only an effective mechanism in pathogenesis of CD. We suggest that the functional significance of FAS expression should be investigated by methods of evaluating apopitosis in patients with İELAG and NSD who has more FAS expression when compared to CD . Also in the detection of number of İEL in suspected cases routine use of CD3 immunohistochemical evaluation may be useful.
    VL  - 2
    IS  - 5
    ER  - 

    Copy | Download

Author Information
  • Iskenderun State Hospital, Department of Pathology, Hatay, Turkey

  • Iskenderun State Hospital ,Department of Family Medicine, Hatay, Turkey

  • Bozok University Faculty of Medicine, Department of Internal Medicine, Yozgat, Turkey

  • Iskenderun State Hospital, Department of Internal Medicine, Hatay, Turkey

  • Sections