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New IBD markers: definition of disease heterogeneity

  • S. R. Targan

Abstract

The objective of this chapter is to relate recent findings that support the use of molecular and cellular techniques to define subsets of patients with inflammatory bowel disease (IBD). An example of the potential of using these methods to define disease subgroups by genetic and subclinical markers is an ‘aggressive’ form of rheumatoid arthritis, which recently has been shown to express a specific HLA-DR4 allele1. This subgroup of patients with rheumatoid arthritis is defined clinically by a progressively active course that is resistant to standard therapy, including corticosteroids. Such patients do, however, respond very well to treatment with the immune suppressant, methotrexate. Those patients with the HLA-DR4 allele are now placed immediately on methotrexate. Thus, this description of a subgroup of patients has led to a completely altered treatment protocol, and is the first instance where a genetic marker is being used to define a subset of patients for treatment with a selected therapy in an immunologically mediated disease. In ulcerative colitis and Crohn’s disease, subsets of patients may also be defined by genetic and subclinical markers that reflect specific types of mucosal inflammation, and each type may represent a unique opportunity for individualized treatment approaches.

Keywords

Ulcerative Colitis Patient Juvenile Rheumatoid Arthritis Antineutrophil Cytoplasmic Antibody Pouchitis Disease Activity Index Individualize Treatment Approach 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Weyand CM, Hikok K, Conn DL, Goronzy JJ. The influence of HLA-DRB1 genes on disease severity in rheumatoid arthritis. Ann Intern Med. 1992; 117: 801–6.PubMedGoogle Scholar
  2. 2.
    Pociot F, Briant L, Jongeneel CV et al. Association of tumor necrosis factor (TNF) and class II major histocompatibility complex alleles with the secretion of TNF-a and TNF-ß by human mononuclear cells: a possible link to insulin-dependent diabetes. Eur J Immunol. 1993; 23: 224–31.PubMedCrossRefGoogle Scholar
  3. 3.
    Nepom B, Nepom G, Schaller J et al. Characterization of specific HLA DR4-associated histocompatibility markers in patients with juvenile rheumatoid arthritis. J Clin Invest. 1984; 74: 287–91.PubMedCrossRefGoogle Scholar
  4. 4.
    Yang H-Y, Rotter JI, Toyoda H et al. Ulcerative colitis: a genetically heterogeneous disorder defined by genetic (HLA class II) and subclinical (anti-neutrophil cytoplasmic antibodies (ANCA)) markers. J Clin Invest. 1993; 92: 1080–4.PubMedCrossRefGoogle Scholar
  5. 5.
    Shanahan F, Duerr R, Landers C et al. Neutrophil autoantibodies in ulcerative colitis. A family study with evidence for genetic heterogeneity. Gastroenterology. 1992; 103: 456–61.PubMedGoogle Scholar
  6. 6.
    Yang H, Vora D, Targan S, Toyoda H, Beaudet A, Rotter JI. Genetic heterogeneity within UC and Crohn’s disease defined by anti-neutrophil cytoplasmic antibodies (ANCAs) and intercellular adhesion molecule-I (ICAM-1) polymorphisms. Gastroenterology. 1994 (In press) (abstr.).Google Scholar
  7. 7.
    Targan SR, Landers C, Vidrich A, MacDermott R P. Perinuclear antineutrophil cytoplasmic antibodies (p-ANCA) are spontaneously produced by B-cells from involved and uninvolved mucosa of ulcerative colitis (UC) patients (Submitted).Google Scholar
  8. 8.
    Targan SR, Landers C, Vidrich A, MacDermott RP. Perinuclear antineutrophil cytoplasmic antibodies (p-ANCA) are spontaneously produced by B-cells from involved and uninvolved mucosa of ulcerative colitis (UC) patients. Gastroenterology. 1994 (In press) (abstr.).Google Scholar
  9. 9.
    Sandborn WJ, Tremaine WJ, Batts K, Pemberton JH, Phillips SF. Definition of pouchitis following ileal pouch anal anastomosis (IPAA): a pouchitis disease activity index. Gastroenterology. 1993; 104: A774.Google Scholar
  10. 10.
    Vecchi M, Gionchetti P, Bianchi MB et al. p-ANCA reactivity in ulcerative colitis patients with and without pouchitis after proctocolectomy. Gastroenterology. 1993; 104: A796.Google Scholar
  11. 11.
    Sandborn WJ, Landers CJ, Steiner BL, Tremaine WJ, Targan SR. The prevalence of antineutrophil cytoplasmic antibody (ANCA) is unexpectedly high in patients with treatment-resistant, left-sided ulcerative colitis (UC). Gastroenterology. 1994 (In press) (abstr.).Google Scholar
  12. 12.
    Yang H-Y, Vora D, Targan S, Toyoda H, Beaudet A, Rotter J. Association of intercellular adhesion molecule-1 (ICAM-1) polymorphisms with subsets of inflammatory bowel disease (IBD) stratified by antineutrophil cytoplasmic antibodies (ANCA) (Submitted).Google Scholar

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© Kluwer Academic Publishers and Axcan Pharma, Inc. 1994

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  • S. R. Targan

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