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Immunopathogenesis of inflammatory bowel diseaseMy primary research interests are immunopathogenesis of inflammatory bowel disease (IBD). We have focused on the autoimmune aspects of IBD and have identified several mucosal antigens associated with the disease. Earlier. we isolated disease-specific autoantibody in ulcerative colitis (UC) and using this antibody. we identified an Mr 40k colon epithelial protein (P40) which acts as an autoantigen in UC. Specific autoantibodies to P40 were detected in patients with UC and cotton top tamarins with colitis. Most recently. we have purified P40 to homogeneity. sequenced 2 peptides after proteolytic digestion. and demonstrated that P40 belongs to the cytoskeletal protein tropomyosin family. We have also developed several monoclonal antibodies against epithelial peptides. and using one of the monoclonal antibodies. 7E12H12. we have localized the epitope to colonic enterocytes and not in 13 other epithelial tissues including small intestinal enterocytes. There was a gradient in the expression of the 7E12H12 reactivity caudally with maximum expression in the rectum. Using the 7E12H12 monoclonal antibody. a crossreactive. unique peptide was detected in the colon. skin and biliary epithelium. ciliary body epithelium in the eye and chondrocytes in the joints. organs commonly involved in UC. Patients with primary sclerosing cholangitis have autoantibody against this epitope. Current focus of the laboratory is to fully sequence the autoantigenic protein(s). clone the gene encoding the protein. and investigate cellular and humoral immune responses against the peptides/epitopes derived from the protein. Development of an animal model using the autoantigen(s) is also being pursued. Selected PublicationsBajpai M, Liu J, Geng X, Souza RF, Amenta PS, Das KM. (2008) Repeated exposure to acid and bile selectively induces colonic phenotype expression in a heterogeneous Barrett's epithelial cell line. Lab Invest. 88(6):643-51. Yantiss RK, Das KM, Farraye FA, Odze RD. (2008) Alterations in the immunohistochemical expression of Das-1 and CG-3 in colonic mucosal biopsy specimens helps distinguish ulcerative colitis from Crohn disease and from other forms of colitis. Am J Surg Pathol. 32(6):844-50. Watari J, Das KK, Amenta PS, Tanabe H, Tanaka A, Geng X, Lin JJ, Kohgo Y, Das KM. (2008) Ebert EC, Geng X, Lin J, Das KM. (2006) Autoantibodies against human tropomyosin isoform 5 in ulcerative colitis destroys colonic epithelial cells through antibody and complement-mediated lysis. Cell Immunol. 244(1):43-49. Mirza ZK, Sastri B, Lin JJ, Amenta PS, Das KM. (2006) Autoimmunity against human tropomyosin isoforms in ulcerative colitis: localization of specific human tropomyosin isoforms in the intestine and extraintestinal organs. Inflamm Bowel Dis. 12(11):1036-43. Cohen HD, Das KM. (2006) The metabolism of mesalamine and its possible use in colonic diverticulitis as an anti-inflammatory agent. J Clin Gastroenterol. 40(7 Suppl 3):S150-4. Review. Sun JH. Das KK. Amenta PS. Yokota K. Watari J. Sato T. Kohgo Y. Das KM. (2006) Preferential expression of cyclooxygenase-2 in colonic-phenotype of gastric intestinal metaplasia: association with helicobacter pylori and gastric carcinoma. J Clin Gastroenterol. 40(2):122-8. Shen E. Das K. (2005) Infliximab for ulcerative colitis. J Clin Gastroenterol. 39(10):920. Sun JH. Das KM. (2005) Low-dose oral methotrexate for maintaining Crohn's disease remission: where we stand. J Clin Gastroenterol. 39(9):751-6. Kovvali G. Das KM. (2005) Molecular mimicry may contribute to pathogenesis of ulcerative colitis. FEBS Lett. 579(11):2261-6. Glazier KD. Palance AL. Griffel LH. Das KM. (2005) The ten-year single-center experience with 6-mercaptopurine in the treatment of inflammatory bowel disease. J Clin Gastroenterol. 39(1):21-6. Das KM. (2004) Is foe your friend? Inflamm Bowel Dis. 10(5):693. Shen EH. Das KM. (2004) Current therapeutic recommendations: infliximab for ulcerative colitis. J Clin Gastroenterol. 38(9):741-5. Subbaramaiah K. Yoshimatsu K. Scherl E. Das KM. Glazier KD. Golijanin D. Soslow RA. Tanabe T. Naraba H. Dannenberg AJ. (2004) Microsomal prostaglandin E synthase-1 is overexpressed in inflammatory bowel disease. Evidence for involvement of the transcription factor Egr-1. J Biol Chem. 279(13):12647-58. Biancone L. Palmieri G. Lombardi A. Colantoni A. Tonelli F. Das KM. Pallone F. (2003) Tropomyosin expression in the ileal pouch: a relationship with the development of pouchitis in ulcerative colitis. Am J Gastroenterol. 98(12):2719-26. Fisher RS. Bromer MQ. Thomas RM. Cohen S. Krevsky B. Horwitz B. Glazier KD. Das K. Das KM. (2003) Predictors of recurrent specialized intestinal metaplasia after complete laser ablation. Am J Gastroenterol. 98(9):1945-51. Rogge-Wolf C. Seldenrijk CA. Das KM. Timmer R. Breumelhof R. Smout AJ. Amenta PS. Griffel LH. (2002) Prevalence of mabDAS-1 positivity in biopsy specimens from the esophagogastric junction. Am J Gastroenterol. 97(12):2979-85. Zimmerman RL. Das KM. Burke MA. Young NA. Solomides CC. Bibbo M. (2002) The clinical utility of the Das-1 monoclonal antibody in identifying adenocarcinoma of the colon metastatic to the liver in fine-needle aspiration tissue. Cancer. 96(6):370-3. Zimmerman RL. Das KM. Fogt F. Burke M. Murakata LA. (2002) The Das-1 immunostain is useful for discriminating metastatic colon adenocarcinoma from cholangiocarcinoma and hepatocellular carcinoma. Oncol Rep. 9(6):1369-72. Lin JL. Geng X. Bhattacharya SD. Yu JR. Reiter RS. Sastri B. Glazier KD. Mirza ZK. Wang KK. Amenta PS. Das KM. Lin JJ. (2002) Isolation and sequencing of a novel tropomyosin isoform preferentially associated with colon cancer. Gastroenterology. 123(1):152-62. Das KM. Farag SA. (2000) Current medical therapy of inflammatory bowel disease. World J Gastroenterol. 6(4):483-489. |
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