Ubiquitous Colonic Ileal Metaplasia Consistent with the Diagnosis of Crohn’s Colitis among Indeterminate Colitis Cohorts
Main Article Content
Abstract
Background: Inadequate differentiated diagnostic features of predominantly colonic inflammatory bowel diseases i.e., ulcerative colitis and Crohn’s colitis, may lead to inexact diagnosis of “indeterminate colitis”. About 15% of indeterminate colitis patients are diagnosed at colonoscopy, in colonic biopsies, and/or at colectomy. Managing outcomes of indeterminate colitis, given its unpredictable clinical presentation, depends on future diagnosis of colitis, Crohn’s colitis or ulcerative colitis.
Objective: Overview the diagnostic efficacy of ectopic colonic ileal metaplasia and human α-defens 5 (DEFA5 alias HD5) for accurate delineation of indeterminate colitis into authentic Crohn’s colitis and/ or ulcerative colitis.
Design: We describe a targeted protein for potentially differentiating indeterminate colitis into an accurate clinical subtype diagnosis of inflammatory bowel diseases i.e., ulcerative colitis and Crohn’s colitis.
Patients: Twenty-one patients with the clinically inexact diagnosis of indeterminate colitis were followed, reassessed and data analyzed.
Main outcome measures: We observed that (i) some patients had their original diagnosis changed from indeterminate colitis to either ulcerative colitis or Crohn’s colitis; and (ii) human α-defensin 5 is aberrantly overexpressed in Crohn’s colitis.
Results: Fifteen of the twenty-one (71.4%) patients with indeterminate colitis had their inconclusive diagnosis changed; nine patients changed to ulcerative colitis and six to Crohn’s colitis. In human colon surgical samples, Human α-defensin-5 was significantly upregulated in Crohn’s colitis. In addition, Human α-defensin 5 processing enzyme, matrix metalloptotease-7 was inversely expressed compared to Human α- Defensin 5.
Limitation: Due to the sequence homology of the α-defensin class of proteins, preceding efforts to raise antibodies (Abs) against DEFA5 have limitations to produce adequate specificity. The Abs used in previous assays recognizes the α-defensins, active α-defensins 5 and inactive pro- α-defensins 5. Monoclonal antibodies (mAbs) to determine specificity and sensitivity of α-defensins 5, which is diagnostic of CC disease, and NOT other α-defensins is the limitation to overcome.
Conclusion: It is feasible to differentiate ulcerative colitis from Crohn’s colitis among patients with inexact diagnosis of indeterminate colitis using Human α-defensin 5 as a molecular biosignature delineator.
Keywords:
inflammatory bowel disease, indeterminate colitis, Ulcerative colitis, Crohn’s colitis, Human alpha-defensin 5
Article Details
How to Cite
M'KOMA, Amosy E.; BREAUX, William A.; BRAGG, Maya A..
Ubiquitous Colonic Ileal Metaplasia Consistent with the Diagnosis of Crohn’s Colitis among Indeterminate Colitis Cohorts.
Medical Research Archives, [S.l.], v. 11, n. 8, aug. 2023.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/4188>. Date accessed: 27 dec. 2024.
doi: https://doi.org/10.18103/mra.v11i8.4188.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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2. Carvalho RS, Abadom V, Dilworth HP, Thompson R, Oliva-Hemker M, Cuffari C. Indeterminate colitis: a significant subgroup of pediatric IBD. Inflammatory bowel diseases. 2006;12(4):258-62. DOI: 10.1097/01.MIB.0000215093.62245.b9.
3. M'Koma AE, Seeley EH, Washington MK, Schwartz DA, Muldoon RL, Herline AJ, Wise PE, Caprioli RM. Proteomic profiling of mucosal and submucosal colonic tissues yields protein signatures that differentiate the inflammatory colitides. Inflamm Bowel Dis. 2011;17(4):875-83. DOI: 10.1002/ibd.21442.
4. Seeley EH, Washington MK, Caprioli RM, M'Koma AE. Proteomic patterns of colonic mucosal tissues delineate Crohn's colitis and ulcerative colitis. Proteomics Clin Appl. 2013;7(7-8):541-9. DOI: 10.1002/prca.201200107.
5. Williams AD, Korolkova OY, Sakwe AM, Geiger TM, James SD, Muldoon RL, et al. Human alpha defensin 5 is a candidate biomarker to delineate inflammatory bowel disease. PloS one. 2017;12(8):e0179710. DOI: 10.1371/journal.pone.0179710.
6. M'Koma AE, Wise PE, Muldoon RL, Schwartz DA, Washington MK, Herline AJ. Evolution of the restorative proctocolectomy and its effects on gastrointestinal hormones. Int J Colorectal Dis. 2007;22(10):1143-63. DOI: 10.1007/s00384-007-0331-x.
7. Shen B, Remzi FH, Brzezinski A, Lopez R, Bennett AE, Lavery IC, et al. Risk factors for pouch failure in patients with different phenotypes of Crohn's disease of the pouch. Inflammatory bowel diseases. 2008;14(7):942-8. DOI: 10.1002/ibd.20409
8. Shen B, Remzi FH, Lavery IC, Lashner BA, Fazio VW. A proposed classification of ileal pouch disorders and associated complications after restorative proctocolectomy. Clin Gastroenterol Hepatol. 2008;6(2):145-58. DOI: 10.1016/j.cgh.2007.11.006.
9. Ricardo AP, Kayal M, Plietz MC, Khaitov S, Sylla P, Dubinsky MC, et al. Predictors of pouch failure: A tertiary care inflammatory bowel disease centre experience. Colorectal Dis. 2023. DOI: 10.1111/codi.16589.
10. Shen B. Crohn's disease of the ileal pouch: reality, diagnosis, and management. Inflammatory bowel diseases. 2009;15(2):284-94. DOI: 10.1002/ibd.20661
11. Malaty HM, Mehta S, Abraham B, Garnett EA, Ferry GD. The natural course of inflammatory bowel disease-indeterminate from childhood to adulthood: within a 25 year period. Clin Exp Gastroenterol. 2013;6:115-21. DOI: 10.2147/CEG.S44700
12. Malaty HM, Fan X, Opekun AR, Thibodeaux C, Ferry GD. Rising incidence of inflammatory bowel disease among children: a 12-year study. J Pediatr Gastroenterol Nutr. 2010;50(1):27-31. DOI: 10.1097/MPG.0b013e3181b99baa.
13. Keighley MR. The final diagnosis in pouch patients for presumed ulcerative colitis may change to Crohn's disease: patients should be warned of the consequences. Acta Chir Iugosl. 2000;47(4 Suppl 1):27-31. PMID: 11432239
14. Lawrance IC, Fiocchi C, Chakravarti S. Ulcerative colitis and Crohn's disease: distinctive gene expression profiles and novel susceptibility candidate genes. Hum Mol Genet. 2001;10(5):445-56. DOI: 10.1093/hmg/10.5.445.
15. Wang C, Shen M, Gohain N, Tolbert WD, Chen F, Zhang N, et al. Design of a potent antibiotic peptide based on the active region of human defensin 5. J Med Chem. 2015;58(7):3083-93. DOI: 10.1021/jm501824a.
16. Chileveru HR, Lim SA, Chairatana P, Wommack AJ, Chiang IL, Nolan EM. Visualizing attack of Escherichia coli by the antimicrobial peptide human defensin 5. Biochemistry. 2015;54(9):1767-77. DOI: 10.1021/bi501483q.
17. Wilson CL, Schmidt AP, Pirila E, Valore EV, Ferri N, Sorsa T, et al. Differential Processing of {alpha}- and {beta}-Defensin Precursors by Matrix Metalloproteinase-7 (MMP-7). J Biol Chem. 2009;284(13):8301-11. DOI: 10.1074/jbc.M809744200.
18. Vandenbroucke RE, Vanlaere I, Van Hauwermeiren F, Van Wonterghem E, Wilson C, Libert C. Pro-inflammatory effects of matrix metalloproteinase 7 in acute inflammation. Mucosal Immunol. 2014;7(3):579-88. DOI: 10.1038/mi.2013.76.
19. Mastroianni JR, Costales JK, Zaksheske J, Selsted ME, Salzman NH, Ouellette AJ. Alternative luminal activation mechanisms for paneth cell alpha-defensins. J Biol Chem. 2012;287(14):11205-12. DOI: 10.1074/jbc.M111.333559.
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