Digestive Diseases and Sciences

, Volume 40, Issue 4, pp 805–811 | Cite as

Decreased mucosal IgA levels in ileum of patients with chronic ulcerative colitis

  • Luca Cicalese
  • Richard H. Duerr
  • Michael A. Nalesnik
  • Peter F. Heeckt
  • Kenneth K. W. Lee
  • Wolfgang H. Schraut
Intestinal Disorders, Inflammatory Bowel Disease, Immunology And Microbiology


Patients with chronic ulcerative colitis (CUC) are known to have decreased spontaneous IgA secretion by colonic mononuclear cells. The aim of this study was to determine whether a similar alteration exists in the apparently healthy ileum of patients with CUC. The concentration of IgA was measured in the supernatant from homogenized mucosal ileal biopsies using a sandwich-type ELISA. The concentration of IgA was significantly (P=0.025) decreased in the ileum of patients with CUC (N=24) in comparison to normal ileum (N=10). The number of mucosal IgA-containing mononuclear cells (MNC) was also determined using an avidin-biotin-immunoperoxidase technique on paraffin-embedded ileal sections. Although reduced, the number of positive cells and their distribution was not significantly different in the ileum of patients with CUC (N=20) when compared to normal ileum (N=10). We suggest that decreased mucosal IgA levels are a panintestinal condition in CUC and that this is a primary alteration rather than a secondary response to the inflammatory process. Considering the role of IgA, we propose that decreased mucosal IgA levels in CUC may predispose to the disease by a reduction of the immune-mediated exclusion mechanism and/or by an impairment of the down-regulation of the inflammatory response.

Key words

immunoglobulin A ulcerative colitis ileum 


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  1. 1.
    MacDermott RP, Nash GS, Bertovich MJ, Seiden MV, Bragdon MJ, Baile MG: Alterations of IgM, IgG, and IgA synthesis and secretion by peripheral blood and intestinal mononuclear cells from patients with ulcerative colitis and Crohn's disease. Gastroenterology 81:844–852, 1981PubMedGoogle Scholar
  2. 2.
    MacDermott RP, Beale MG, Alley CD, Nash GS, Bertovich MJ, Bragdon MJ: Synthesis and secretion of IgA, IgM and IgG by peripheral blood mononuclear cells in human disease states, by isolated human intestinal mononuclear cells, and by human bone marrow mononuclear cells from ribs. Ann NY Acad Sci 83:498–509, 1983Google Scholar
  3. 3.
    MacDermott RP, Nash GS, Bertovich MJ, Mohrman RF, Kodner IJ, Delacroix DL, Vaerman J: Altered patterns of secretion of monomeric Ig-A and Ig-A subclass 1 by intestinal mononuclear cells in inflammatory bowel disease. Gastroenterology 91:379–385, 1986PubMedGoogle Scholar
  4. 4.
    MacDermott RP, Nash GS, Nahm MH: Antibody secretion by human intestinal mononuclear cells from normal controls and inflammatory bowel disease patients. Immunol Invest 18(1–4):449–457, 1989PubMedGoogle Scholar
  5. 5.
    Wu KC, Mahida YR, Priddle JD, Jewell DP: Immunoglobulin production by isolated intestinal mononulear cells from patients with ulcerative colitis and Crohn's disease. Clin Exp Immunol 78:37–41, 1989PubMedGoogle Scholar
  6. 6.
    Brandtzaeg P: Immunopathology of inflammatory bowel disease.In Inflammatory Bowel Disease. RP MacDermott, WF Stenson, (eds). New York, Elsevier, 1992, pp 102–136Google Scholar
  7. 7.
    Rognum TO, Elgjo K, Fausa O, Brandtzaeg P: Immunohistochemical evaluation of carcinoembryonic antigen, secretory component, and epithelial Ig-A in ulcerative colitis with dysplasia. Gut 23:123–133, 1982PubMedGoogle Scholar
  8. 8.
    Gelzayd EA, Kraft SC, Fitch FW, Kirsner JB: Distribution of immunoglobulins in human rectal mucosa. Ulcerative colitis and abnormal mucosal control subjects. Gastroenterology 54(3):341–347, 1968PubMedGoogle Scholar
  9. 9.
    O'Donoghue DP, Kumar P: Rectal Ig-E cells in inflammatory bowel disease. Gut 20:149–153, 1979PubMedGoogle Scholar
  10. 10.
    Meuwissen SGM, Feltkamp-Vroom TM, Brutel de la Riviere A, Von Dem Borne AEGKR, Tytgat GN: Analysis of the lympho-plasmacytic infiltrate in Crohn's disease with special reference to identification of lymphocyte-subpopulations. Gut 17:770–780, 1976PubMedGoogle Scholar
  11. 11.
    Badr-El-Din S, Trejdosiewicz LK, Heatley RV, Losowsky MS: Local immunity in ulcerative colitis: Evidence for defective secretory Ig-A production. Gut 29:1070–1075, 1988PubMedGoogle Scholar
  12. 12.
    Crama-Bohbouth G, Pena AS, Verspaget HW, Zon A, Biemont I, Weterman IT, Lamers CBHW: Immunological findings in whole and parotid saliva of patients with ulcerative colitis and healthy controls. Hepato-Gastroenterol 36:185–187, 1989Google Scholar
  13. 13.
    Castro GA, Arntzen CJ: Immunophisiology of the gut: A research frontier for integrative studies of the common mucosal immune system. Am J Physiol 265(Gastrointest Liver Physiol 28):G599-G610, 1993PubMedGoogle Scholar
  14. 14.
    Castro GA: Gut immunophisiology: Regulatory pathways within a common mucosal immune system. News Physiol Sci 4:59–64, 1989Google Scholar
  15. 15.
    McDermott MR, Bienenstock J: Evidence for a common mucosal immunologic system. I. Migration of b immunoblasts into respiratory and genital tissues. J Immunol 122:1892–1898, 1979PubMedGoogle Scholar
  16. 16.
    Mestecky J: The common mucosal immune system and current strategies for induction of immune responses in external secretions. J Clin Immunol 7:265–276, 1987PubMedGoogle Scholar
  17. 17.
    Engstrom JF, Arvanitakis C, Sagawa A, Abdou NI: Secretory immunoglobulin deficiency in a family with inflammatory bowel disease. Gastroenterology 74:747–751, 1978PubMedGoogle Scholar
  18. 18.
    Wagner A, Eichmann D: Primar-sklerosierende Cholangitis bei isoliertem Ig-A-Mangel. Schweiz Med Wochenschr 119:835–838, 1989PubMedGoogle Scholar
  19. 19.
    Kartheuser AH, Dozois RR, Wiesner RH, LaRusso NF, Ilstrup DM, Schleck CD: Complications and risk factors after ileal pouch-anal anastomosis for ulcerative colitis associated with primary sclerosing cholangitis. Ann Surg 217(4):314–320, 1993PubMedGoogle Scholar
  20. 20.
    Wiesner RH, LaRusso NF: Clinicopathologic features of the syndrome of primary sclerosing cholangitis. Gastroenterology 79:200–206, 1980PubMedGoogle Scholar
  21. 21.
    LaRusso NF, Wiesner RH, Ludwig J, MacCarty RL: Primary sclerosing cholangitis. N Engl J Med 310:899–903, 1984PubMedGoogle Scholar
  22. 22.
    Helzberg JH, Petersen JM, Boyer JL: Improved survival with primary sclerosing cholangitis: A review of clinicopathological features and comparison of symptomatic and asymptomatic patients. Gastroenterology 92:1869–1875, 1987PubMedGoogle Scholar
  23. 23.
    Cangemi JR, Wiesner RH, Beaver SJ, Ludwig J, MacCarty RL, Dozois RR, Zinmeister AR, LaRusso NF: Effect of proctocolectomy for chronic ulcerative colitis on the natural history of primary sclerosing cholangitis. Gastroenterology 96:790–794, 1989PubMedGoogle Scholar
  24. 24.
    Denison H, Wallerstedt S: Bacterial overgrowth after high-dose corticosteroid treatment. Scand J Gastroenterol 24(5):561–564, 1989PubMedGoogle Scholar
  25. 25.
    Lamm ME: Cellular aspects of immunoglobulin A. Adv Immunol 22:223–290, 1976.PubMedGoogle Scholar
  26. 26.
    Williams RC, Gibbons RJ: Inhibition of bacterial adherence by secretory immunoglobulin A: A mechanism of antigen disposal. Science 177:697–699, 1972PubMedGoogle Scholar
  27. 27.
    Snyder JD, Walker WA: Structure and function of intestinal mucin: Developmental aspects. Int Arch Allergy Appl Immunol 82:351–356, 1987PubMedGoogle Scholar
  28. 28.
    Walker WA, Wu M, Bloch KJ: Stimulation by immune complexes of mucus release from goblet cells of the rat small intestine. Science 97:370–371, 1977Google Scholar
  29. 29.
    Mazanec MB, Nedrud JG, Kaetzel CS, Lamm ME: A three-tiered view of the role of Ig-A in mucosal defense. Immunol Today 14(9):430–435, 1993PubMedGoogle Scholar
  30. 30.
    Russel MW, Mansa B: Complement-fixing properties of human Ig-A antibodies. Scand J Immunol 30:175–183, 1989PubMedGoogle Scholar
  31. 31.
    Imai H, Chen A, Wyatt RJ, Rifai A: Lack of complement activation by human Ig-A immune complexes. Clin Exp Immunol 73:479–483, 1988PubMedGoogle Scholar
  32. 32.
    Mestecky J, Russel MW, Jackson S, Brown TA: The human Ig-A system: A reassessment. Clin Immunol Immunopathol 40:105–114, 1986PubMedGoogle Scholar
  33. 33.
    Griffis JMcL, Jarris GA: Interaction of serum Ig-A with complement components: The molecular basis of Ig-A blockade. Adv Exp Med Biol 216B:1303–1309, 1987PubMedGoogle Scholar
  34. 34.
    Griffis JM: Bactericidal activity of meningococcal antisera. Blocking by Ig-A of lytic antibody in human convalescent sera. J Immunol 114:1779–1784, 1975PubMedGoogle Scholar
  35. 35.
    Wilton JM: Suppression by Ig-A of Ig-G-mediated phagocytosis by human polymorpho-nuclear leucocytes. Clin Exp Immunol 34:423–428, 1978PubMedGoogle Scholar
  36. 36.
    Ruthlein J, Ibe M, Burghardt W, Mossner J, Auer IO: Immunoglobulin G (Ig-G, Ig-G1, and Ig-G2) determinations from endoscopic biopsy specimens in control, Crohn's disease, and ulcerative colitis subjects. Gut 33:507–512, 1992PubMedGoogle Scholar
  37. 37.
    Halstensen TS, Mollnes TE, Garred P, Fausa O, Brandtzaeg P: Surface epithelium related activation of complement differs in Crohn's disease and ulcerative colitis. Gut 33:902–908, 1992PubMedGoogle Scholar
  38. 38.
    Santos MC, Thompson JS, Late complication of the ileal pouch-anal anastomosis. Am J Gastroenterol 88:3–10, 1993PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1995

Authors and Affiliations

  • Luca Cicalese
    • 1
  • Richard H. Duerr
    • 1
  • Michael A. Nalesnik
    • 1
  • Peter F. Heeckt
    • 1
  • Kenneth K. W. Lee
    • 1
  • Wolfgang H. Schraut
    • 1
  1. 1.From the Departments of Surgery, Medicine, Division of Gastroenterology and Hepatology, and PathologyUniversity of Pittsburgh School of MedicinePittsburgh

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