Skip to main content
SpringerLink
Log in

Relationship of Extraintestinal Involvements in Inflammatory Bowel Disease (New Insights into Autoimmune Pathogenesis)

  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Extraintestinal manifestations in patients withinflammatory bowel disease (IBD) are quite common (about25%) and careful clinical observation and statisticalanalysis during the last five decades have demonstrated that in colitis-associatedextraintestinal complications, the organs most commonlyinvolved are the biliary tract, joints, skin, and eyes.However, almost all organs can be involved in IBD. Some of the extraintestinal manifestations mayprecede IBD, although the majority accompany theunderlying disease and are influenced by its activity.Prompt recognition of extracolonic organ involvement in IBD is important because of the relativerefractoriness of the disease and a possible increase inmorbidity and mortality. The identified pathogeneticautoimmune mechanisms include genetic susceptibility, cytokine imbalances, antigenic display ofautoantigen, aberrant self-recognition, andimmunopathogenetic autoantibodies against organ-specificcellular antigen(s) shared by colon and extracolonicorgans. Microbes may play an important role, probablyby molecular mimicry.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Monsen U, Sorstad J, Hellers G, Johansson C: Extracolonic diagnose s in ulcerative colitis: An epidemiological study. Am J Gastroenterol 85:711-716, 1990

    Google Scholar 

  2. Greenstein AJ, Janowiz HD, Sachar DB: The extra-intestinal complications of Crohn' s disease and ulcerative colitis. A study of 700 patients. Medicine 55:401-412, 1976

    Google Scholar 

  3. Rankin GB, Watts HD, Melnyk CS, Kelley ML Jr: National cooperative Crohn' s disease study: Extra-intestinal manifestations and perianal complications. Gastroenterology 77:914-920, 1979

    Google Scholar 

  4. Scott WW Jr, Fishman EK, Kuhlman JE, Caskey CI, O'Brien JJ, Walia GS, Bayless TM: Computed tomography evaluation of the sacroiliac joints in Crohn disease. Int Skeletal Soc 19:207-210, 1990

    Google Scholar 

  5. Wright R, Lumsden K, Luntz MH, Sevel D, True love SC: Abnormalities of the sacroiliac joints and uve itis in ulcerative colitis. Q J Med 134:229-236, 1965

    Google Scholar 

  6. Gregory B, Ho VC: Cutaneous manife stations of gastrointe stinal disorders. Part II. J Am Acad Dermatol 26:371-383, 1992

    Google Scholar 

  7. Lohmuller JL, Pemberton JH, Dozois RR, Ilstrup D, van-Heerden J: Pouchitis and extraintestinal manifestations of inflammatory bowel disease after ileal pouch-anal anastomosis. Ann Surg 211:622-629, 1990

    Google Scholar 

  8. Bianchi CA: Cutaneous manife stations of the malabsorption syndrome. Med Cutan Ibero Lat Am 12:277-285, 1984

    Google Scholar 

  9. Paller AS: Cutaneous changes associated with inflammatory bowel disease. Pediatr Dermatol 3:439-445, 1986

    Google Scholar 

  10. Levitt MD, Ritchie JK, Lennard-Jones JE, Phillips RKS: Pyoderma gangrenosum in inflammatory bowel disease. Br J Surg 78:676-678, 1991

    Google Scholar 

  11. Mir-Madjlessi SH, Taylor JS, Farmer RG: Clinical course and evolution of e rythema nodosum and pyoderma gangre nosum in chronic ulcerative colitis: A study of 42 patients. Am J Gastroenterol 80:615-620, 1985

    Google Scholar 

  12. Carp JM, Onuma E, Das KM, Gottlieb AB: Intravenous cyclosporine therapy in the treatment of pyoderma gangrenosum secondary to Crohn's disease. Cutis 60:135-138, 1997

    Google Scholar 

  13. Controversies in IBD. Inflam Bowel Disease 4:68-73, 1998

    Google Scholar 

  14. Ely PH, Utsinger PD: Clinical observations and immunologic abnormalities following bowel bypass surge ry. J Am Acad De rmatol 2:529-530, 1980

    Google Scholar 

  15. Wiesner RH, LaRusso NJ: Clinicopathologic feature s of the syndrome of primary scle rosing cholangitis. Gastroenterology 79:200-206, 1980

    Google Scholar 

  16. Dew MJ, Thompson H, Allan RN: The spectrum of hepatic dysfunction in inflammatory bowel disease. Q J Med 48:113-135, 1979

    Google Scholar 

  17. Lindor KD, Wiesner RH, LaRusso NF: Recent advances in the manageme nt of primary scle rosing cholangitis. Semin Liv Dis 7:322-327, 1987

    Google Scholar 

  18. Olsson R, Danielsson A, Jarnerot G, Lindstrom E, Loof L, Rolny P, Ryden B-O, Tysk C, Wallerstedt S: Prevalence of primary sclerosing cholangitis in patients with ulcerative colitis. Gastroente rology 100:1319-1323, 1991

    Google Scholar 

  19. Cangemi JR, Wiesner RH, Beaver SJ, Ludwig J: The effect of proctocolectomy for chronic ulcerative colitis on the natural history of primary sclerosing cholangitis. Gastroenterology 96:790-794, 1989

    Google Scholar 

  20. Mir-Madjlessi SH, Farmer RG, Sivak MV: Bile duct carci-noma in patients with ulcerative colitis. Dig Dis Sci 32:145-154, 1987

    Google Scholar 

  21. Nashan B, Schlitt HJ, Tusch G, Oldhafer KJ, Ringe B, Wagner S, Pichlmayer R: Biliary malignancie s in primary scle rosing cholangitis. Hepatology 23:1105-1111, 1996

    Google Scholar 

  22. Nichols JC, Gores GJ, LaRusso NF, Wiesner RH, Magorney DM, Ritts Jr RE: Diagnostic role of serum CA 19-9 for cholangiocarcinoma in patients with primary scle rosing cholangitis. Mayo Clin Proc 68:874-879, 1993

    Google Scholar 

  23. Broome U, Lofberg R, Lundqvist K, Veress B: Subclinical time span of inflammatory bowel disease in patients with primary sclerosing cholangitis. Dis Colon Rectum 38:1301-1305, 1995

    Google Scholar 

  24. Brentnall TA, Haggitt RC, Rabinovitch PS, Kimmey MB, Crispin DA, Kowdley KV, Bronner MP, Rubin CE: Risk and natural history of colonic neoplastic progression in patients with primary sclerosing cholangitis and ulcerative colitis. Gastroenterology 108:A452, 1995

    Google Scholar 

  25. Salmon JF, Wright JP, Murray ADN: Ocular inflammation in Crohn' s disease. Ophthalmology 98:480-484, 1991

    Google Scholar 

  26. Hofley P, Roarty J, McGinnity G, Griffi ths AM, Marcon M, Krafts SP: Asymptomatic uveitis with chronic inflammatory bowel diseases. J Pediatr Nutr 17:397-400, 1993

    Google Scholar 

  27. Levy PJ, Tabares AH, Olin JW: Lower extremity arterial occlusions in young patients with Crohn' s colitis and premature athe rosclerosis: report of six case s. Am J Gastro 92:494-497, 1997

    Google Scholar 

  28. Kreise l W, Wolf LM, Grotz W, Grieshaber M: Renal tubular damage: an extraintestinal manife station of chronic inflammatory bowel disease. Eur J Gastro and Hep 8:461-468, 1996

    Google Scholar 

  29. Lossos A, River Y, Eliakim A, Steiner I: Neurologic aspects of inflammatory bowel disease. 45(3 Pt I):416-421, 1995

    Google Scholar 

  30. Louis E, Louis R, Drion V, Bonnet V, Lamproye A, Radermecker M, Belaiche J: Increased frequency of bronchial hyperresponsiveness in patients with inflammatory bowel disease. Allergy 50:729-733, 1995

    Google Scholar 

  31. Das KM, Eastwood MA, McManus JPA, Sircus W: Adve rse reactions during salicylazosulfapyridine therapy and the relationship with drug metabolism and ace tylator phenotype. N Engl J Med 289:491-495, 1973

    Google Scholar 

  32. Sartor RB: Cytokines in intestinal inflammation: Pathophysiological and clinical conside rations. Gastroente rology 106:533-539, 1994

    Google Scholar 

  33. Snook JA, de Silva HJ, Jewell DP: The association of autoimmune disorders with inflammatory bowel disease. Q J Med 269:835-840, 1989

    Google Scholar 

  34. Padolsky DK: Inflammatory bowel disease: Part 1. N Engl J Med 325:928-937, 1991

    Google Scholar 

  35. Brandtzaeg P, Halstensen TS, Kett K: Immunopathology of inflammatory bowel disease. In Inflammatory Bowel Disease, Current Topics in Gastroenterology. RP MacDermott, WF Stenson (eds). London, Elsevier, 1992, pp 95-136

    Google Scholar 

  36. Whiteside TL, Lasky S, Si L, VanThiel DH: Immunologic analysis of mononucle ar cells in liver tissues and blood or patients with primary scle rosing cholangitis. Hepatology 5:468-474, 1985

    Google Scholar 

  37. McFarlane IG, Wojcicka BM, Tsantoulas DC, Portmann BC, Eddleston ALWF, Williams R: Leucocyte migration inhibition in response to biliary antigens in primary biliary cirrhosis, sclerosing cholangitis and other chronic liver diseases. Gastroenterology 76:1333-1340, 1979

    Google Scholar 

  38. Minuk GY, Angus M, Brickman CM, Lawley TJ, Frank MM, Hoofnagle JH, Jones EA: Abnormal clearance of immune complexe s from the circulation of patients with primary scle-rosing cholangitis. Gastroenterology 88:166-170, 1985

    Google Scholar 

  39. Senaldi G, Donaldson PT, Magrin S, Farrant JM, Alexander GJM, Vergani D, Williams R: Activation of the complement system in primary sclerosing cholangitis. Gastroenterology 97:1430-1434, 1989

    Google Scholar 

  40. Duerr RH, Targan SR, Landers CJ, LaRusso NF, Lindsay KL, Weisner RH, Shanahan F: Neutrophil cytoplasmic antibodies: A link between primary scle rosing cholangitis and ulcerative colitis. Gastroenterology 100:1385-1391, 1991

    Google Scholar 

  41. Broberger O, Perlmann P: Autoantibodies in human ulcerative colitis. J Exp Med 110:657-674, 1959

    Google Scholar 

  42. Lazarus GS, Goldsmith LA, Rocklin RE, Pinals RS, deBuisseret JP, David JR, Draper W: Pyoderma gangrenosum, altered delayed hypersensitivity, and polyarthritis. Arch Dermatol 105:46-51, 1972

    Google Scholar 

  43. Bentley-Phillips CB, Cooper RC, Hallett AF: Pharmacologi-cal modulation of neutrophil phagocytic function in a patient with recurrent sepsis, pyoderma gangre nosum and impaired phagocytosis. Br J Dermatol 106:687-695, 1982

    Google Scholar 

  44. Sartor RB: Microbial factors in the pathogenesis of Crohn's disease, ulcerative colitis and expe rimental intestinal inflammation. In Inflammatory Bowel Disease. JB Kirsner, RJ Shorter (eds). Philadelphia, Lea & Febiger, 1995, pp 96-124

    Google Scholar 

  45. MacDermott RP, Elson CO: Mucosal immunology I. Gastroenterol Clin North Am 20:397-627, 1991

    Google Scholar 

  46. Sadlack B, Merz H, Schorle H, Schimpl A, Feller AC, Horak I: Ulcerative colitis-like disease in mice with a disrupted interleukin-2 gene. Cell 75:253-261, 1993

    Google Scholar 

  47. Kuhn R, Lohler J, Rennick D, Rajewsky K, Muller W: Interleukin-10-deficient mice develop chronic enterocolitis. Cell 75:263-274, 1993

    Google Scholar 

  48. Mombaerts P, Mizoguchi E, Grusby MJ, Glimcher LH, Bhan AK, Tonegawa S: Spontaneous development of inflammatory bowel disease in T cell receptor mutant mice. Cell 75:274–282, 1993

    Google Scholar 

  49. Hammer RE, Maika SD, Richardson JA, Tang JP, Taurog JD: Spontaneous inflammatory disease in transgenic rats expre ssing HLA-B27 and human beta 2m: An animal model of HLA-B27-associated human disorders. Cell 63:1099-1112, 1990

    Google Scholar 

  50. Breban M, Hammer RE, Richardson JA, Taurog JD: Transfer of the inflammatory disease of HLA-B27 transgenic rats by bone marrow engraftment. J Exp Med 178:1607-1616, 1993

    Google Scholar 

  51. Taurog JD, Richardson JA, Croft JT, Simmons WA, Zhou M, Fernandez-Sueiro JL, Balish E: The ge rmfree state preve nts deve lopment of gut and joint inflammatory disease in HLAB27 transgenic rats. J Exp Med 180:2359-2364, 1994

    Google Scholar 

  52. Sartor RB, Cromartie WJ, Powell DW, Schwab JH: Granulomatous ente rocolitis induced in rats by purified bacterial cell wall fragments. Gastroenterology 89:587-595, 1985

    Google Scholar 

  53. Lichtman SN, Keku J, Clark RL, Schwab JH, Sartor RB: Biliary tract disease in rats with expe rimental small bowel bacte rial ove rgrowth. Hepatology 13:766-772, 1990

    Google Scholar 

  54. Bangaru B, Morecki R, Glaser JH, Gartner LM, Horwitz MS: Comparative studies of biliary atre sia in the human newborn and reovirus-induced cholangitis in weanling mice. Lab Invest 43:452-462, 1980

    Google Scholar 

  55. Minuk GY, Rascanin N, Paul RW, Lee PWK, Buchan K, Kelly JK: Reovirus type 3 infection in patients with primary biliary cirrhosis and primary sclerosing cholangitis. J Hepatol 5:8-13, 1987

    Google Scholar 

  56. Mizoguchi A, Mizoguchi E, Chiba C, Spiekermann GM, Tonegawa S, Nagler-Anderson C, Bhan AK: Cytokine imbalance and autoantibody production in T cell receptor-a mutant mice with inflammatory bowel disease. J Exp Med 183:847-856, 1996

    Google Scholar 

  57. Mizoguchi A, Mizoguchi E, Chiba C, Bhan AK: Role of appendix in the development of inflammatory bowel disease in TCR-a mice. J Exp Med 184:707-715, 1996

    Google Scholar 

  58. Hollander GA, Simpson SJ, Mizoguchi E, Nichogiannopoulou A, She J, Gutierrez-Ramos J-C, Bhan AK, Burakoff SJ, Wang B, Terhorst C: Seve re colitis in mice with abe rrant thymic se lection. Immunity 3:27-38, 1995

    Google Scholar 

  59. Chapman RW, Cottone M, Selby WS, Shepherd HA, Sherlock S, Jewell DP: Serum autoantibodies in ulcerative colitis and primary sclerosing cholangitis. Gut 27:86-91, 1986

    Google Scholar 

  60. Broberger O, Perlmann P: In vitro studies of ulcerative colitis, I. Reactions of patients' serum with human fetal colon cells in tissue culture. J Exp Med 117:705-715, 1963

    Google Scholar 

  61. Hibi TB, Aiso M, Ishikawa M: Circulating antibodies to the surface antigens on colon epithelial ce lls in ulcerative colitis. Clin Exp Immunol 54:163-168, 1983

    Google Scholar 

  62. Aronson RA, Cooke SL, Roche JK: Sensitization to epithelial antigens in chronic mucosal inflammatory disease. I. Purification, characte rization and immunoreactivity of murine epithelial ce ll-associated components (ECAC). J Immunol 131:2796-2844, 1983

    Google Scholar 

  63. Scott MG, Nahm MH, Macke K, Nash GS, Bertovich MJ, MacDermott RP: Spontaneous secretion of IgG subclasse s by intestinal mononuclear ce lls; difference s between ulcerative colitis, Crohn' s disease and controls. Clin Exp Immunol 66:209-215, 1986

    Google Scholar 

  64. Halstensen TS, Mollnes TE, Garred P, Fausa O, Brandtzaeg P: Epithelial deposition of immunoglobulin G1 and activate d complement (C3b and terminal compleme nt complex) in ulce rative colitis. Gastroenterology 98:1264-1271, 1990

    Google Scholar 

  65. Tan EM: Autoantibodies in pathology and cell biology. Cell 67:841-842, 1991

    Google Scholar 

  66. Wuche rpfennig KW, Strominger JL: Molecular mimicry in T cell-mediated autoimmunity: Viral peptides activate human T ce ll clones specific for myelin basic protein. Cell 80:695-705, 1995

    Google Scholar 

  67. Naparstek Y, Plotz PH: The role of autoantibodies in autoimmune disease. Annu Rev Immunol 11:79-104, 1993

    Google Scholar 

  68. Liblau RS, Singer SM, McDevitt HO: Th1 and Th2 CD41 T ce lls in the pathogene sis of organ-spe cifi c autoimmune diseases. Immunol Today 16:34-38, 1995

    Google Scholar 

  69. Elson CJ, Barker RN, Thompson SJ, Williams NA: Immunologically ignorant autoreactive T cells, epitope spreading and repertoire limitation. Immunol Today 16:71-76, 1995

    Google Scholar 

  70. Liao L, Sindhwani R, Rojkind M, Factor S, Leinwand L, Diamond B: Antibody-mediated autoimmune myocarditis depends on genetically determined target organ sensitivity. J Exp Med 181:1123-1131, 1995

    Google Scholar 

  71. New N, Rose NR, Beisel KW, Herskowitz A, Gurri-Glass G, Craig SW: Cardiac myosin induces myocarditis in genetically predisposed mice. J Immunol 139:3630–3636, 1987

    Google Scholar 

  72. Murphy KM, Heimberger AB, Loh DY: Induction by antigen of intrathymic apoptosis of CD4+ CD8+ TCRLO thymocyte s in vivo. Science 250:1720-1723, 1990

    Google Scholar 

  73. Oldstone MBA, Nerenberg M, Southern P, Price J, Lewicki H: Virus infection trigge rs insulin-dependent diabetes mellitus in a transgenic model: Role of antiself (virus) immune response. Cell 65:319-331, 1991

    Google Scholar 

  74. Zinkernage l RM, Pircher HP, Ohashi P, Oehen S, Odermatt B, Mak T, Arnheiter H, Burki K, Hengartner H: T and B cell tolerance and responses to viral antigens in transgenic mice: Implications for the pathogenesis of autoimmune versus immunopathological disease. Immunol Rev 122:133-171, 1991

    Google Scholar 

  75. Kagnoff MF, Austin RK, Hubert JJ, Bernardin JE, Kasarda JJ: Possible role for a human adenovirus in the pathogenesis of ce liac disease. J Exp Med 160:1544-1557, 1984

    Google Scholar 

  76. Takle GB, Hudson L: Autoimmunity and Chagas' disease. Curr Top Microbiol Immunol 145:79-92, 1989

    Google Scholar 

  77. Tian J, Lehmann PV, Kaufman DL: T ce ll cross-re activity between coxsackie virus and glutamate decarboxylase is associated with a murine diabetes susceptibility allele. J Exp Med 180:1979-1984, 1994

    Google Scholar 

  78. Schwimmbeck PL, Dyrberg T, Drachman DB, Oldstone MB: Molecular mimicry and myasthenia gravis. An autoantigenic site of the ace tylcholine re ceptor alpha-subunit that has biologic activity and reacts immunochemically with herpes simplex virus. J Clin Invest 84:1174-1180, 1989

    Google Scholar 

  79. Fenderson PG, Fischetti VA, Cunningham MW: Tropomyosin share s immunologic epitopes with group A streptococcal M proteins. J Immunol 142:2475-2480, 1989

    Google Scholar 

  80. Quigley EMM, LaRusso NJ, Ludwig J, MacSween RNM, Birnie GG, Watkinson G: Familial occurrence of primary sclerosing cholangitis and ulcerative colitis. Gastroenterology 85:1160-1165, 1983

    Google Scholar 

  81. Satsangi J, Grootscholten C, Holt H, Jewell DP: Clinical patterns of familial inflammatory bowel disease. Gut 38:738-741, 1996

    Google Scholar 

  82. Toyoda H, Wang S-J, Yang H-Y, Redford A, Magalong D, Tyan D, McElree CK, Pressman SR, Shanahan F, Targan SR, Rotter JI: Distinct associations of HLA class II genes with inflammatory bowel disease. Gastroenterology 104:741-748, 1993

    Google Scholar 

  83. Fujita K, Naito S, Okabe N, Yao T: Immunological studies in Crohn' s disease. 1. Association with HLA systems in the Japanese. J Clin Lab Immunol 14:99-102, 1984

    Google Scholar 

  84. Chapman RW, Varghese Z, Gaul R, Patel G, Kikinon N, Sherlock S: Association of primary scle rosing cholangitis with HLA-B8. Gut 24:38-41, 1983

    Google Scholar 

  85. Prochazka EJ, Terasaki PI, MinSik Park DVM, Goldstein LI, Busuttil RW: Association of primary sclerosing cholangitis with HLA-DRw52a. N Engl J Med 322:1842-1844, 1990

    Google Scholar 

  86. Roussomoustakaki J, Satsangi J, Welsh K, Louis E, Fanning G, Targan S, Landers C, Jewell DP: Genetic marke rs may predict disease behaviour in patients with ulcerative colitis.Gastroenterology 112:1845-1853, 1997

    Google Scholar 

  87. Seibold F, Weber P, Klein R, Berg PA, Wiedmann KH: Clinical significance of antibodies against neutrophils in patients with inflammatory bowel disease primary sclerosing cholangitis. Gut 33:657-662, 1992

    Google Scholar 

  88. Seibold F, Slametschka D, Gregor M, Weber P: Neutrophil autoantibodies: A genetic marke r in primary scle rosing cholangitis and ulcerative colitis. Gastroenterology 107:532-536, 1994

    Google Scholar 

  89. Nagant de Deuxchaisnes C, Huaux JP, Fiasse R, DeBruyere M: Ankylosing spondylitis, sacroiliitis, regional enteritis and HL-A27. Lancet 1:1238-1239, 1974

    Google Scholar 

  90. Morris RI, Metzger AL, Bluestone R, Terasaki PI: HLADAS W27: A use ful discriminator in the arthropathies of inflammatory bowel disease. N Engl J Med 290:1117-1119, 1974

    Google Scholar 

  91. Haslock I: Arthritis and Crohn's disease: A family study. Ann Rheum Dis 32:479-486, 1973

    Google Scholar 

  92. Selby WS, Janossy G, Mason DY, Jewell DP: Expression of HLA-DR antigens by colonic epithelium in inflammatory bowel disease. Clin Exp Immunol 53:614-618, 1983

    Google Scholar 

  93. Broome U, Glaumann H, Hultcrantz R, Forsum U: Distribution of HLA-DR, HLA-DP, HLA-DQ antigens in liver tissue from patients with primary sclerosing cholangitis. Scand J Gastroenterol 25:54-58, 1990

    Google Scholar 

  94. Weyand C, Xie C, Goronzy J: Homozygosity for the HLADRB1 alleles se lects for extraarticular manife stations in RA. J Clin Invest 89:2033-2039, 1992

    Google Scholar 

  95. Das KM, Dubin R, Nagai T: Isolation and characte rization of colonic tissue bound antibodies from patients with idiopathic ulcerative colitis. Proc Natl Acad Sci 75:4528-4532, 1978

    Google Scholar 

  96. Takahashi F, Das KM: Isolation and characte rization of a colonic autoantigen specifically recognized by colon tissuebound IgG from idiopathic ulcerative colitis. J Clin Invest 76:311-318, 1985

    Google Scholar 

  97. Das KM, Dasgupta A, Mandal A: Autoimmunity to cytoske le tal protein tropomyosin(s): A new clue to the pathogenetic mechanism for ulcerative colitis. J Immunol 150:2487-2493, 1993

    Google Scholar 

  98. Biancone L, Monteleone G, Marasaco R, Pallone F: Autoimmunity to tropomyosin isoforms in ulcerative colitis (UC) patients and unaffected relatives. Clin Exp Immunol 113:198-205, 1998

    Google Scholar 

  99. Sakamaki S, Hayashi S, Takayanagi N, Niitsu Y: Autoantibodies in sera of patients with UC recognize tropomyosin peptide associate d with HLA-DPw9. Gastroente rology 110:A1007, 1996

    Google Scholar 

  100. Biancone L, Mandal A, Yang H, Dasgupta T, Paoluzi AO, Marcheggiano A, Paoluzi P, Pallone F, Das KM: Production of immunoglobulin G and G1 antibodies to cytoskele tal protein by lamina propria ce lls in ulcerative colitis. Gastroenterology 109:3-12, 1995

    Google Scholar 

  101. Das KM, Sakamaki S, Vecchi M, Diamond B: The production and characte rization of monoclonal antibodies to a human colonic antigen associated with ulcerative colitis: Cellular localization of the antigen using the monoclonal antibody. J Immunol 139:77-84, 1987

    Google Scholar 

  102. Das KM, Vecchi M, Sakamaki S: A shared and unique epitope(s) on human colon, skin and biliary epithelium detected by a monoclonal antibody. Gastroenterology 98:464-469, 1990

    Google Scholar 

  103. Bhagat S, Das KM: A shared and unique peptide in human colon, eye and joint detected by a novel monoclonal antibody. Gastroenterology 107:103-108, 1994

    Google Scholar 

  104. Halstensen TS, Das KM, Brandtzaeg P: Epithelial deposits of immunoglobulin G1 and activated compleme nt co-localize with the Mr 40K colonic autoantigen in ulcerative colitis. Gut 34:650-657, 1993

    Google Scholar 

  105. Hassan T, Kanisawa Y, Meyers S, Dasgupta A, Das KM: Expre ssion of a unique protein on colon cancer cells that reacts with a nove l monoclonal antibody and ulcerative colitis serum. Clin Exp Immunol 100:457-462, 1995

    Google Scholar 

  106. Das KM, Lin JJ-C, Dasgupta A, Yoshizaki N, Basu J, Geng X, Kesari K: Cell surface display of tropomyosin (TM), a putative autoantigen in ulcerative colitis (UC), is dependent on a colon epithelial-specifi c glycoprote in (CEP). Gastroenterology 112:A955, 1997

    Google Scholar 

  107. Geng X, Biancone L, Dai HH, Lin J, Yoshizaki N, Dasgupta A, Pallone F, Das KM: Tropomyosin isoforms in intestinal mucosa: Production of autoantibodies to tropomyosin isoforms in ulcerative colitis. Gastroenterology 114:912-922, 1998

    Google Scholar 

  108. Marks M, Borra S, Nandiwada K, Das KM: Co-expre ssion of human tropomyosin isoform 5 and a nove l colon epithelial protein (CEP) in the colon epithelium and extracolonic organs commonly involved in ulcerative colitis. Gastroenterology 114:A1032, 1998

    Google Scholar 

  109. Dohlman JG, Lupas A, Carson M: Long charge-rich helices in systemic autoantigens. Biochem Phys Res Commun 195:686-696, 1993

    Google Scholar 

  110. Dasgupta A, Mandal A, Das KM: Circulating immunoglobulin G1 antibody in patients with ulcerative colitis against the colonic epithelial protein detected by a nove l monoclonal antibody. Gut 35:1712-1717, 1994

    Google Scholar 

  111. 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, 1992

    Google Scholar 

  112. Brandtzaeg P: Autoimmunity and ulcerative colitis: Can two enigmas make sense together? Gastroenterology 109:307-312, 1995

    Google Scholar 

  113. Mandal A, Dasgupta A, Jeffers L, Squillante L, Hyder S, Reddy R, Schiff E, Das KM: Autoantibodies in sclerosing cholangitis against a shared epitope in biliary and colon epithelium. Gastroenterology 106:185-192, 1994

    Google Scholar 

  114. Theofilopoulos AN: The basis of autoimmunity: Part 1. Mechanisms of aberrant self-recognition. Immunol Today 16:90-98, 1995

    Google Scholar 

  115. Yeatman N, Sachs J, Bottazzo GF: AutoimmunityÐ towards the year 2001. Immunol Today 13:239-240, 1992

    Google Scholar 

  116. Roth R, Nakamura T, Mamula MJ: B7 costimulation and autoantigen specifi city enable B cells to activate autoreactive T cells. J Immunol 157:2924-2931, 1996

    Google Scholar 

  117. Strober W, Ehrhardt RO: Chronic intestinal inflammation: An unexpe cted outcome in cytokine or T ce ll receptor mutant mice. Cell 75:203-205, 1993

    Google Scholar 

  118. Alarcon-Segovia D, Ruiz-Arguelles A, Liorente L: Broken dogma: Penetration of autoantibodies into living cells. Immunol Today 17:163-164, 1996

    Google Scholar 

Download references

Authors
  1. Kiron M. Das
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Das, K.M. Relationship of Extraintestinal Involvements in Inflammatory Bowel Disease (New Insights into Autoimmune Pathogenesis). Dig Dis Sci 44, 1–13 (1999). https://doi.org/10.1023/A:1026629528233

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1026629528233

Search

Navigation