Digestive Diseases and Sciences

, Volume 41, Issue 12, pp 2493–2498 | Cite as

Multiple sclerosis patients have peripheral blood CD45RO+ B cells and increased intestinal permeability

  • Bruce Yacyshyn
  • Jon Meddings
  • Daniel Sadowski
  • Mary Beth Bowen-Yacyshyn
Intestinal Disorders, Inflammatory Bowel Disease, And Irritable Bowel Syndrome


Increased intestinal permeability and the CD45RO isoform expression of the leukocyte common antigen on peripheral blood CD20+ B cells are found in Crohn's disease. Others have observed that multiple sclerosis (MS) patients may have an increased risk of coacquisition of Crohn's disease. The aim of this study was to identify an association between these diseases using peripheral blood CD45 isoform expression and intestinal permeability in MS. Lactulose/mannitol permeability and peripheral blood CD20+ B cell CD45RO expression were defined in healthy controls, MS patients, and patients coincidentally affected by MS and Crohn's or MS and ulcerative colitis (UC). Five of 20 MS patients had increased intestinal permeability, a finding not previously reported. High levels of CD45RO were found on circulating CD20+ B cells from patients with MS. This has not been reported previously in MS and is found in very few other conditions. Eight patients with coincident MS and Crohn's disease or MS and UC were studied. Coincident MS and UC patients expressed CD45RO on CD20+ B cells, a finding not identified in UC patients alone. A subgroup of MS patients has increased intestinal permeability. These patients express CD45RO CD20+ B cells, also found in Crohn's disease.

Key words

differentiation antigens leukocyte common antigen MS intestinal physiology inflammatory bowel disease 


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  1. 1.
    Pinchbeck BR, Kirdeikis J, Thomson ABR: Inflammatory bowel disease in northern Alberta. An epidemiologic study. J Clin Gastroenterol 10:505–515, 1988PubMedGoogle Scholar
  2. 2.
    Kurtzke JF: Epidemiology of multiple sclerosis.In Multiple Sclerosis, JF Hallpike CWM Adams, WW Tourtelotte (eds). Baltimore, Williams & Wilkins, 1983, pp 47–95Google Scholar
  3. 3.
    Demaine AG: The molecular biology of autoimmune disease. Immunol Today 10:357–361, 1989PubMedGoogle Scholar
  4. 4.
    Wucherpfennig KW, Weiner HL, Hafler DA: T-cell recognition of myelin basic protein. Immunol Today 12:277–282, 1991PubMedGoogle Scholar
  5. 5.
    Minuk GY, Lewkonia RM: Possible familial association of multiple sclerosis and inflammatory bowel disease. N Engl J Med 314(9):586, 1986PubMedGoogle Scholar
  6. 6.
    Purrmann J, Arendt G, Cleveland S, Borchard F, Furst N, Gemsa R, Bertrams J, Hengels KJ: Association of Crohn's disease and multiple sclerosis. Is there a common background? J Clin Gastroenterol 14(1):43–46, 1991Google Scholar
  7. 7.
    Sadovnick AD, Paty DW, Yannakoulias G: Concurrence of multiple sclerosis and inflammatory bowel disease. N Engl J Med 321:762–763, 1989Google Scholar
  8. 8.
    Kitchin LI, Knobler RL, Friedman LS: Crohn's disease in a patient with multiple sclerosis. J Clin Gastroenterol 13:331–334, 1991PubMedGoogle Scholar
  9. 9.
    Agranoff D, Schon F: Are focal white matter lesions in patients with inflammatory bowel disease linked to multiple sclerosis? Lancet 346(8968):190–191, 1995Google Scholar
  10. 10.
    Geissler A, Andus T, Roth M, Kullmann F, Caesar I, Held P, Gross V, Feuerbach S, Scholmerich J: Focal white matter lesions in brain of patients with inflammatory bowel disease. Lancet 345(8954):897–898, 1995PubMedGoogle Scholar
  11. 11.
    Warren KG, Katz I: Purification of primary antibodies of the myelin basic protein antibody cascade from multiple sclerosis patients. Immunoreactivity studies with homologous and heterologous antigens. Clin Invest Med 15:18–29, 1992PubMedGoogle Scholar
  12. 12.
    Mayer L, Eisenhardt D: Lack of induction of suppressor T-cells by intestinal epithelial cells from patients with inflammatory bowel disease. J Clin Invest 86:1255–1260, 1990PubMedGoogle Scholar
  13. 13.
    Sun JB, Olsson T, Wang WZ, Xiao BG, Kostulas V, Fredrikson S, Ekre HP, Link H: Autoreactive T and B-cells responding to myelin proteolipid protein in multiple sclerosis and controls. Eur J Immunol 21:1461–1468, 1991PubMedGoogle Scholar
  14. 14.
    Mix E, Olsson T, Correale J, Baig S, Kostulas V, Olsson O, Link H: B-cells expressing CD5 are increased in cerebrospinal fluid of patients with multiple sclerosis. Clin Exp Immunol 79:21–27, 1990PubMedGoogle Scholar
  15. 15.
    Martino G, Olsson T, Fredrikson S, Hojeberg B, Kostulas V, Grimaldi LM, Link H: Cells producing antibodies specific for myelin basic protein region 70–89 are predominant in cerebrospinal fluid from patients with multiple sclerosis. Eur J Immunol 21:2971–2976, 1991PubMedGoogle Scholar
  16. 16.
    Michielsens B, Walravens M, Vermylen J, Carton H: Diagnostic significance of antinuclear antibodies in neurologic patients. Acta Neurol Scand 84:102–106, 1991PubMedGoogle Scholar
  17. 17.
    Carr RI, Weldon P, Sadi D, Murray TJ: Autoantibodies toβ-endorphin in patients with multiple sclerosis (MS). Clin Invest Med 15 (Suppl):A-16, 1992Google Scholar
  18. 18.
    MacDermott RP, Nash GS, Aver IO, Shlien R, Kewis BS, Madassery J, Nahn MH: Alterations in serum immunoglobulin G subclasses in patients with ulcerative colitis and Crohn's disease. Gastroenterology 96:764–768, 1989PubMedGoogle Scholar
  19. 19.
    Yacyshyn BR, Pilarski LM: Expression of CD45RO on circulating CD19+ B-cells in Crohn's disease. Gut 34:1698–1704, 1993PubMedGoogle Scholar
  20. 20.
    Pilarski LM, Jensen GS: Expression of CD45 isoforms (leukocyte common antigen) and adhesion molecules during normal and abnormal human B-lymphocyte development.In Advances in Molecular and Cellular Immunology, Vol 1B, B Singh (ed). Greenwich, CT, JAI, 1993, pp 75–118Google Scholar
  21. 21.
    Thomas ML: The leukocyte common antigen family. Annu Rev Immunol 7:339–369, 1989PubMedGoogle Scholar
  22. 22.
    Pilarski LM, Gillitzer R, Zola H, Shortman K, Scollay R: Definition of the thymic generative lineage by selective expression of high molecular weight isoforms of CD45 (T200). Eur J Immunol 19:589–597, 1989PubMedGoogle Scholar
  23. 23.
    Jensen GS, Poppema S, Mant MJ, Pilarski LM: Transition in CD45 isoform expression during differentiation of normal and abnormal B-cells. Int Immunol 1:229–236, 1989PubMedGoogle Scholar
  24. 24.
    Pilarski LM, Jensen GS: Monoclonal circulating B-cells in multiple myeloma. A continuously differentiating possibly invasive population as defined by expression of CD45 isoforms and adhesion molecules. Hematol/Oncol Clin North Am 6:297–322, 1992Google Scholar
  25. 25.
    Yacyshyn BR: Activated CD19 B-cell lamina propria lymphocytes in ulcerative colitis. Immunol Cell Biol 71:265–274, 1993PubMedGoogle Scholar
  26. 26.
    Yacyshyn BR, Meddings JB: CD45RO expression on circulating CD19+ B-cells in Crohn's disease correlates with intestinal permeability. Gastroenterology 108:132–137, 1995PubMedGoogle Scholar
  27. 27.
    Poser CM, Paty DW, Scheinberg L, McDonald WI, Davis FA, Ebers GC, Johnson KP, Sibley WA, Silberberg DH, Tourtellotte WW: New diagnostic criteria for multiple sclerosis: Guidelines for research protocols. Ann Neurol 13:227–231, 1983PubMedGoogle Scholar
  28. 28.
    Harvey J, Jones DB, Wright DH: Leukocyte common antigen expression on T-cells in normal and inflamed human gut. Immunology 68:13–17, 1989PubMedGoogle Scholar
  29. 29.
    Rodriguez M, Scheithauer BW, Forbes G, Kelly PJ: Oligodendrocyte injury is an early event in lesions of multiple sclerosis. Mayo Clin Proc 68:627–636, 1993PubMedGoogle Scholar
  30. 30.
    Yacyshyn BR, Lazarovits A, Tsai V, Matejko K: Crohn's disease, ulcerative colitis and normal intestinal lymphocytes express integrins in dissimilar patterns. Gastroenterology 107:1364–1371, 1994PubMedGoogle Scholar
  31. 31.
    Sobel RA, Mitchell ME, Fondren G: Intercellular adhesion molecule-1 (ICAM-1) in cellular immune reactions in the human central nervous system. Am J Pathol 136(6):1309–1316, 1990PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1996

Authors and Affiliations

  • Bruce Yacyshyn
    • 1
    • 2
  • Jon Meddings
    • 1
    • 2
  • Daniel Sadowski
    • 1
    • 2
  • Mary Beth Bowen-Yacyshyn
    • 1
    • 2
  1. 1.From the Department of Medicine, Division of GastroenterologyUniversity of AlbertaEdmontonCanada
  2. 2.Department of Medicine, Division of GastroenterologyUniversity of CalgaryCalgaryCanada

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