Human alpha defensin 5 is a candidate biomarker to delineate inflammatory bowel disease

Amanda D. Williams, Olga Y. Korolkova, Amos M. Sakwe, Timothy M. Geiger, Samuel D. James, Roberta L. Muldoon, Alan Joseph Herline, J. Shawn Goodwin, Michael G. Izban, Mary K. Washington, Duane T. Smoot, Billy R. Ballard, Maria Gazouli, Amosy E. M’Koma

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Inability to distinguish Crohn’s colitis from ulcerative colitis leads to the diagnosis of indeterminate colitis. This greatly effects medical and surgical care of the patient because treatments for the two diseases vary. Approximately 30 percent of inflammatory bowel disease patients cannot be accurately diagnosed, increasing their risk of inappropriate treatment. We sought to determine whether transcriptomic patterns could be used to develop diagnostic biomarker(s) to delineate inflammatory bowel disease more accurately. Four patients groups were assessed via whole-transcriptome microarray, qPCR, Western blot, and immunohistochemistry for differential expression of Human α-Defensin-5. In addition, immunohistochemistry for Paneth cells and Lysozyme, a Paneth cell marker, was also performed. Aberrant expression of Human α-Defensin-5 levels using transcript, Western blot, and immunohistochemistry staining levels was significantly upregulated in Crohn’s colitis, p< 0.0001. Among patients with indeterminate colitis, Human α-Defensin-5 is a reliable dif-ferentiator with a positive predictive value of 96 percent. We also observed abundant ectopic crypt Paneth cells in all colectomy tissue samples of Crohn’s colitis patients. In a retrospective study, we show that Human α-Defensin-5 could be used in indeterminate colitis patients to determine if they have either ulcerative colitis (low levels of Human α-Defensin-5) or Crohn’s colitis (high levels of Human α-Defensin-5). Twenty of 67 patients (30 percent) who underwent restorative proctocolectomy for definitive ulcerative colitis were clinically changed to de novo Crohn’s disease. These patients were profiled by Human α-Defensin-5 immunohistochemistry. All patients tested strongly positive. In addition, we observed by both hematoxylin and eosin and Lysozyme staining, a large number of ectopic Paneth cells in the colonic crypt of Crohn’s colitis patient samples. Our experiments are the first to show that Human α-Defensin-5 is a potential candidate biomarker to molecularly differentiate Crohn’s colitis from ulcerative colitis, to our knowledge. These data give us both a potential diagnostic marker in Human α-Defensin-5 and insight to develop future mechanistic studies to better understand crypt biology in Crohn’s colitis.

Original languageEnglish (US)
Article numbere0179710
JournalPloS one
Volume12
Issue number8
DOIs
StatePublished - Aug 2017

Fingerprint

Defensins
inflammatory bowel disease
colitis
Biomarkers
Colitis
Inflammatory Bowel Diseases
biomarkers
Paneth Cells
Ulcerative Colitis
Immunohistochemistry
immunohistochemistry
Muramidase
Patient treatment
Western Blotting
Restorative Proctocolectomy
human alpha-defensin 5
lysozyme
Staining and Labeling
Hematoxylin
Colectomy

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Williams, A. D., Korolkova, O. Y., Sakwe, A. M., Geiger, T. M., James, S. D., Muldoon, R. L., ... M’Koma, A. E. (2017). Human alpha defensin 5 is a candidate biomarker to delineate inflammatory bowel disease. PloS one, 12(8), [e0179710]. https://doi.org/10.1371/journal.pone.0179710

Human alpha defensin 5 is a candidate biomarker to delineate inflammatory bowel disease. / Williams, Amanda D.; Korolkova, Olga Y.; Sakwe, Amos M.; Geiger, Timothy M.; James, Samuel D.; Muldoon, Roberta L.; Herline, Alan Joseph; Goodwin, J. Shawn; Izban, Michael G.; Washington, Mary K.; Smoot, Duane T.; Ballard, Billy R.; Gazouli, Maria; M’Koma, Amosy E.

In: PloS one, Vol. 12, No. 8, e0179710, 08.2017.

Research output: Contribution to journalArticle

Williams, AD, Korolkova, OY, Sakwe, AM, Geiger, TM, James, SD, Muldoon, RL, Herline, AJ, Goodwin, JS, Izban, MG, Washington, MK, Smoot, DT, Ballard, BR, Gazouli, M & M’Koma, AE 2017, 'Human alpha defensin 5 is a candidate biomarker to delineate inflammatory bowel disease', PloS one, vol. 12, no. 8, e0179710. https://doi.org/10.1371/journal.pone.0179710
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 Aug;12(8). e0179710. https://doi.org/10.1371/journal.pone.0179710
Williams, Amanda D. ; Korolkova, Olga Y. ; Sakwe, Amos M. ; Geiger, Timothy M. ; James, Samuel D. ; Muldoon, Roberta L. ; Herline, Alan Joseph ; Goodwin, J. Shawn ; Izban, Michael G. ; Washington, Mary K. ; Smoot, Duane T. ; Ballard, Billy R. ; Gazouli, Maria ; M’Koma, Amosy E. / Human alpha defensin 5 is a candidate biomarker to delineate inflammatory bowel disease. In: PloS one. 2017 ; Vol. 12, No. 8.
@article{2014686f961f4dc08fc9d9f3462e8b87,
title = "Human alpha defensin 5 is a candidate biomarker to delineate inflammatory bowel disease",
abstract = "Inability to distinguish Crohn’s colitis from ulcerative colitis leads to the diagnosis of indeterminate colitis. This greatly effects medical and surgical care of the patient because treatments for the two diseases vary. Approximately 30 percent of inflammatory bowel disease patients cannot be accurately diagnosed, increasing their risk of inappropriate treatment. We sought to determine whether transcriptomic patterns could be used to develop diagnostic biomarker(s) to delineate inflammatory bowel disease more accurately. Four patients groups were assessed via whole-transcriptome microarray, qPCR, Western blot, and immunohistochemistry for differential expression of Human α-Defensin-5. In addition, immunohistochemistry for Paneth cells and Lysozyme, a Paneth cell marker, was also performed. Aberrant expression of Human α-Defensin-5 levels using transcript, Western blot, and immunohistochemistry staining levels was significantly upregulated in Crohn’s colitis, p< 0.0001. Among patients with indeterminate colitis, Human α-Defensin-5 is a reliable dif-ferentiator with a positive predictive value of 96 percent. We also observed abundant ectopic crypt Paneth cells in all colectomy tissue samples of Crohn’s colitis patients. In a retrospective study, we show that Human α-Defensin-5 could be used in indeterminate colitis patients to determine if they have either ulcerative colitis (low levels of Human α-Defensin-5) or Crohn’s colitis (high levels of Human α-Defensin-5). Twenty of 67 patients (30 percent) who underwent restorative proctocolectomy for definitive ulcerative colitis were clinically changed to de novo Crohn’s disease. These patients were profiled by Human α-Defensin-5 immunohistochemistry. All patients tested strongly positive. In addition, we observed by both hematoxylin and eosin and Lysozyme staining, a large number of ectopic Paneth cells in the colonic crypt of Crohn’s colitis patient samples. Our experiments are the first to show that Human α-Defensin-5 is a potential candidate biomarker to molecularly differentiate Crohn’s colitis from ulcerative colitis, to our knowledge. These data give us both a potential diagnostic marker in Human α-Defensin-5 and insight to develop future mechanistic studies to better understand crypt biology in Crohn’s colitis.",
author = "Williams, {Amanda D.} and Korolkova, {Olga Y.} and Sakwe, {Amos M.} and Geiger, {Timothy M.} and James, {Samuel D.} and Muldoon, {Roberta L.} and Herline, {Alan Joseph} and Goodwin, {J. Shawn} and Izban, {Michael G.} and Washington, {Mary K.} and Smoot, {Duane T.} and Ballard, {Billy R.} and Maria Gazouli and M’Koma, {Amosy E.}",
year = "2017",
month = "8",
doi = "10.1371/journal.pone.0179710",
language = "English (US)",
volume = "12",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "8",

}

TY - JOUR

T1 - Human alpha defensin 5 is a candidate biomarker to delineate inflammatory bowel disease

AU - Williams, Amanda D.

AU - Korolkova, Olga Y.

AU - Sakwe, Amos M.

AU - Geiger, Timothy M.

AU - James, Samuel D.

AU - Muldoon, Roberta L.

AU - Herline, Alan Joseph

AU - Goodwin, J. Shawn

AU - Izban, Michael G.

AU - Washington, Mary K.

AU - Smoot, Duane T.

AU - Ballard, Billy R.

AU - Gazouli, Maria

AU - M’Koma, Amosy E.

PY - 2017/8

Y1 - 2017/8

N2 - Inability to distinguish Crohn’s colitis from ulcerative colitis leads to the diagnosis of indeterminate colitis. This greatly effects medical and surgical care of the patient because treatments for the two diseases vary. Approximately 30 percent of inflammatory bowel disease patients cannot be accurately diagnosed, increasing their risk of inappropriate treatment. We sought to determine whether transcriptomic patterns could be used to develop diagnostic biomarker(s) to delineate inflammatory bowel disease more accurately. Four patients groups were assessed via whole-transcriptome microarray, qPCR, Western blot, and immunohistochemistry for differential expression of Human α-Defensin-5. In addition, immunohistochemistry for Paneth cells and Lysozyme, a Paneth cell marker, was also performed. Aberrant expression of Human α-Defensin-5 levels using transcript, Western blot, and immunohistochemistry staining levels was significantly upregulated in Crohn’s colitis, p< 0.0001. Among patients with indeterminate colitis, Human α-Defensin-5 is a reliable dif-ferentiator with a positive predictive value of 96 percent. We also observed abundant ectopic crypt Paneth cells in all colectomy tissue samples of Crohn’s colitis patients. In a retrospective study, we show that Human α-Defensin-5 could be used in indeterminate colitis patients to determine if they have either ulcerative colitis (low levels of Human α-Defensin-5) or Crohn’s colitis (high levels of Human α-Defensin-5). Twenty of 67 patients (30 percent) who underwent restorative proctocolectomy for definitive ulcerative colitis were clinically changed to de novo Crohn’s disease. These patients were profiled by Human α-Defensin-5 immunohistochemistry. All patients tested strongly positive. In addition, we observed by both hematoxylin and eosin and Lysozyme staining, a large number of ectopic Paneth cells in the colonic crypt of Crohn’s colitis patient samples. Our experiments are the first to show that Human α-Defensin-5 is a potential candidate biomarker to molecularly differentiate Crohn’s colitis from ulcerative colitis, to our knowledge. These data give us both a potential diagnostic marker in Human α-Defensin-5 and insight to develop future mechanistic studies to better understand crypt biology in Crohn’s colitis.

AB - Inability to distinguish Crohn’s colitis from ulcerative colitis leads to the diagnosis of indeterminate colitis. This greatly effects medical and surgical care of the patient because treatments for the two diseases vary. Approximately 30 percent of inflammatory bowel disease patients cannot be accurately diagnosed, increasing their risk of inappropriate treatment. We sought to determine whether transcriptomic patterns could be used to develop diagnostic biomarker(s) to delineate inflammatory bowel disease more accurately. Four patients groups were assessed via whole-transcriptome microarray, qPCR, Western blot, and immunohistochemistry for differential expression of Human α-Defensin-5. In addition, immunohistochemistry for Paneth cells and Lysozyme, a Paneth cell marker, was also performed. Aberrant expression of Human α-Defensin-5 levels using transcript, Western blot, and immunohistochemistry staining levels was significantly upregulated in Crohn’s colitis, p< 0.0001. Among patients with indeterminate colitis, Human α-Defensin-5 is a reliable dif-ferentiator with a positive predictive value of 96 percent. We also observed abundant ectopic crypt Paneth cells in all colectomy tissue samples of Crohn’s colitis patients. In a retrospective study, we show that Human α-Defensin-5 could be used in indeterminate colitis patients to determine if they have either ulcerative colitis (low levels of Human α-Defensin-5) or Crohn’s colitis (high levels of Human α-Defensin-5). Twenty of 67 patients (30 percent) who underwent restorative proctocolectomy for definitive ulcerative colitis were clinically changed to de novo Crohn’s disease. These patients were profiled by Human α-Defensin-5 immunohistochemistry. All patients tested strongly positive. In addition, we observed by both hematoxylin and eosin and Lysozyme staining, a large number of ectopic Paneth cells in the colonic crypt of Crohn’s colitis patient samples. Our experiments are the first to show that Human α-Defensin-5 is a potential candidate biomarker to molecularly differentiate Crohn’s colitis from ulcerative colitis, to our knowledge. These data give us both a potential diagnostic marker in Human α-Defensin-5 and insight to develop future mechanistic studies to better understand crypt biology in Crohn’s colitis.

UR - http://www.scopus.com/inward/record.url?scp=85027571857&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85027571857&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0179710

DO - 10.1371/journal.pone.0179710

M3 - Article

C2 - 28817680

AN - SCOPUS:85027571857

VL - 12

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 8

M1 - e0179710

ER -