Evolution of pediatric inflammatory bowel disease unclassified (IBD-U): Incorporated with serological and gene expression profiles

Raguraj Chandradevan, Tatyana Hofmekler, Kajari Mondal, Nusrat Harun, Suresh Venkateswaran, Hari K. Somineni, Cortney R. Ballengee, Mi Ok Kim, Anne Griffiths, Joshua D. Noe, Wallace V. Crandall, Scott Snapper, Shervin Rabizadeh, Joel R. Rosh, Thomas D. Walters, Madeline Bertha, Marla C. Dubinsky, Lee A. Denson, Cary G. Sauer, James F. MarkowitzNeal S. LeLeiko, Jeffrey S. Hyams, Subra Kugathasan

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Inflammatory bowel disease (IBD) mainly consists of Crohn's disease (CD) and ulcerative colitis (UC). About 10%-15% of patients with IBD cannot be firmly diagnosed with CD or UC; hence, they are initially diagnosed as inflammatory bowel disease unclassified (IBD-U). Having a firm diagnosis is clearly preferred to guide treatment choices, and better understanding of the nature of IBD-U is required. Methods: We performed an analysis of a subset of pediatric subjects from an inception IBD cohort of patients initially enrolled in a prospective multicenter study (the RISK study). Initial diagnosis and 2-year follow-up data from the subjects diagnosed with IBD-U were analyzed. An expert panel verified final diagnosis using predefined criteria as a guide. Serological and disease-relevant ileal and rectal tissue gene expression profiles were investigated. The use and the time to initiate anti-TNFα treatment was analyzed among the outcome groups. Results: A total of 1411 subjects were enrolled with initial diagnosis of IBD, and among them, 136 subjects were initially diagnosed as IBD-U at enrollment. And 26% were reclassified as UC and 14% as CD within 2 years of diagnosis, while 60% remained as IBD-U. Of those who were reclassified, there was a 2:1 ratio, UC (n = 35) to CD (n = 19). The molecular and serological features of IBD-U at the end of follow-up were very similar to UC and very different from CD. There was less likelihood of receiving anti-TNFα agents if the diagnosis was IBD-U compared with CD (P < 0.0001). Conclusions: In our cohort, 60% of the IBD-U subjects remained as unclassified at 2 years; of those subsequently classified, a higher percentage followed a course more similar to UC. Most of the IBD-U subjects at diagnosis had serological and molecular signatures that are very similar to UC. Although the atypical presentations made the clinician to make an interim diagnosis of IBD-U, results of the molecular and serological factors performed at the time of diagnosis suggests that they were very similar to UC. However, long-term studies are needed to better understand the natural history and molecular characterization of pediatric onset IBD-U.

Original languageEnglish (US)
Pages (from-to)2285-2290
Number of pages6
JournalInflammatory bowel diseases
Volume24
Issue number10
DOIs
StatePublished - Oct 2018

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Inflammatory Bowel Diseases
Transcriptome
Pediatrics
Ulcerative Colitis
Crohn Disease
Rectal Diseases
Ileal Diseases
Natural History
Multicenter Studies

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Gastroenterology

Cite this

Chandradevan, R., Hofmekler, T., Mondal, K., Harun, N., Venkateswaran, S., Somineni, H. K., ... Kugathasan, S. (2018). Evolution of pediatric inflammatory bowel disease unclassified (IBD-U): Incorporated with serological and gene expression profiles. Inflammatory bowel diseases, 24(10), 2285-2290. https://doi.org/10.1093/ibd/izy136
Chandradevan, Raguraj ; Hofmekler, Tatyana ; Mondal, Kajari ; Harun, Nusrat ; Venkateswaran, Suresh ; Somineni, Hari K. ; Ballengee, Cortney R. ; Kim, Mi Ok ; Griffiths, Anne ; Noe, Joshua D. ; Crandall, Wallace V. ; Snapper, Scott ; Rabizadeh, Shervin ; Rosh, Joel R. ; Walters, Thomas D. ; Bertha, Madeline ; Dubinsky, Marla C. ; Denson, Lee A. ; Sauer, Cary G. ; Markowitz, James F. ; LeLeiko, Neal S. ; Hyams, Jeffrey S. ; Kugathasan, Subra. / Evolution of pediatric inflammatory bowel disease unclassified (IBD-U) : Incorporated with serological and gene expression profiles. In: Inflammatory bowel diseases. 2018 ; Vol. 24, No. 10. pp. 2285-2290.
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title = "Evolution of pediatric inflammatory bowel disease unclassified (IBD-U): Incorporated with serological and gene expression profiles",
abstract = "Background: Inflammatory bowel disease (IBD) mainly consists of Crohn's disease (CD) and ulcerative colitis (UC). About 10{\%}-15{\%} of patients with IBD cannot be firmly diagnosed with CD or UC; hence, they are initially diagnosed as inflammatory bowel disease unclassified (IBD-U). Having a firm diagnosis is clearly preferred to guide treatment choices, and better understanding of the nature of IBD-U is required. Methods: We performed an analysis of a subset of pediatric subjects from an inception IBD cohort of patients initially enrolled in a prospective multicenter study (the RISK study). Initial diagnosis and 2-year follow-up data from the subjects diagnosed with IBD-U were analyzed. An expert panel verified final diagnosis using predefined criteria as a guide. Serological and disease-relevant ileal and rectal tissue gene expression profiles were investigated. The use and the time to initiate anti-TNFα treatment was analyzed among the outcome groups. Results: A total of 1411 subjects were enrolled with initial diagnosis of IBD, and among them, 136 subjects were initially diagnosed as IBD-U at enrollment. And 26{\%} were reclassified as UC and 14{\%} as CD within 2 years of diagnosis, while 60{\%} remained as IBD-U. Of those who were reclassified, there was a 2:1 ratio, UC (n = 35) to CD (n = 19). The molecular and serological features of IBD-U at the end of follow-up were very similar to UC and very different from CD. There was less likelihood of receiving anti-TNFα agents if the diagnosis was IBD-U compared with CD (P < 0.0001). Conclusions: In our cohort, 60{\%} of the IBD-U subjects remained as unclassified at 2 years; of those subsequently classified, a higher percentage followed a course more similar to UC. Most of the IBD-U subjects at diagnosis had serological and molecular signatures that are very similar to UC. Although the atypical presentations made the clinician to make an interim diagnosis of IBD-U, results of the molecular and serological factors performed at the time of diagnosis suggests that they were very similar to UC. However, long-term studies are needed to better understand the natural history and molecular characterization of pediatric onset IBD-U.",
author = "Raguraj Chandradevan and Tatyana Hofmekler and Kajari Mondal and Nusrat Harun and Suresh Venkateswaran and Somineni, {Hari K.} and Ballengee, {Cortney R.} and Kim, {Mi Ok} and Anne Griffiths and Noe, {Joshua D.} and Crandall, {Wallace V.} and Scott Snapper and Shervin Rabizadeh and Rosh, {Joel R.} and Walters, {Thomas D.} and Madeline Bertha and Dubinsky, {Marla C.} and Denson, {Lee A.} and Sauer, {Cary G.} and Markowitz, {James F.} and LeLeiko, {Neal S.} and Hyams, {Jeffrey S.} and Subra Kugathasan",
year = "2018",
month = "10",
doi = "10.1093/ibd/izy136",
language = "English (US)",
volume = "24",
pages = "2285--2290",
journal = "Inflammatory Bowel Diseases",
issn = "1078-0998",
publisher = "John Wiley and Sons Inc.",
number = "10",

}

Chandradevan, R, Hofmekler, T, Mondal, K, Harun, N, Venkateswaran, S, Somineni, HK, Ballengee, CR, Kim, MO, Griffiths, A, Noe, JD, Crandall, WV, Snapper, S, Rabizadeh, S, Rosh, JR, Walters, TD, Bertha, M, Dubinsky, MC, Denson, LA, Sauer, CG, Markowitz, JF, LeLeiko, NS, Hyams, JS & Kugathasan, S 2018, 'Evolution of pediatric inflammatory bowel disease unclassified (IBD-U): Incorporated with serological and gene expression profiles', Inflammatory bowel diseases, vol. 24, no. 10, pp. 2285-2290. https://doi.org/10.1093/ibd/izy136

Evolution of pediatric inflammatory bowel disease unclassified (IBD-U) : Incorporated with serological and gene expression profiles. / Chandradevan, Raguraj; Hofmekler, Tatyana; Mondal, Kajari; Harun, Nusrat; Venkateswaran, Suresh; Somineni, Hari K.; Ballengee, Cortney R.; Kim, Mi Ok; Griffiths, Anne; Noe, Joshua D.; Crandall, Wallace V.; Snapper, Scott; Rabizadeh, Shervin; Rosh, Joel R.; Walters, Thomas D.; Bertha, Madeline; Dubinsky, Marla C.; Denson, Lee A.; Sauer, Cary G.; Markowitz, James F.; LeLeiko, Neal S.; Hyams, Jeffrey S.; Kugathasan, Subra.

In: Inflammatory bowel diseases, Vol. 24, No. 10, 10.2018, p. 2285-2290.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Evolution of pediatric inflammatory bowel disease unclassified (IBD-U)

T2 - Incorporated with serological and gene expression profiles

AU - Chandradevan, Raguraj

AU - Hofmekler, Tatyana

AU - Mondal, Kajari

AU - Harun, Nusrat

AU - Venkateswaran, Suresh

AU - Somineni, Hari K.

AU - Ballengee, Cortney R.

AU - Kim, Mi Ok

AU - Griffiths, Anne

AU - Noe, Joshua D.

AU - Crandall, Wallace V.

AU - Snapper, Scott

AU - Rabizadeh, Shervin

AU - Rosh, Joel R.

AU - Walters, Thomas D.

AU - Bertha, Madeline

AU - Dubinsky, Marla C.

AU - Denson, Lee A.

AU - Sauer, Cary G.

AU - Markowitz, James F.

AU - LeLeiko, Neal S.

AU - Hyams, Jeffrey S.

AU - Kugathasan, Subra

PY - 2018/10

Y1 - 2018/10

N2 - Background: Inflammatory bowel disease (IBD) mainly consists of Crohn's disease (CD) and ulcerative colitis (UC). About 10%-15% of patients with IBD cannot be firmly diagnosed with CD or UC; hence, they are initially diagnosed as inflammatory bowel disease unclassified (IBD-U). Having a firm diagnosis is clearly preferred to guide treatment choices, and better understanding of the nature of IBD-U is required. Methods: We performed an analysis of a subset of pediatric subjects from an inception IBD cohort of patients initially enrolled in a prospective multicenter study (the RISK study). Initial diagnosis and 2-year follow-up data from the subjects diagnosed with IBD-U were analyzed. An expert panel verified final diagnosis using predefined criteria as a guide. Serological and disease-relevant ileal and rectal tissue gene expression profiles were investigated. The use and the time to initiate anti-TNFα treatment was analyzed among the outcome groups. Results: A total of 1411 subjects were enrolled with initial diagnosis of IBD, and among them, 136 subjects were initially diagnosed as IBD-U at enrollment. And 26% were reclassified as UC and 14% as CD within 2 years of diagnosis, while 60% remained as IBD-U. Of those who were reclassified, there was a 2:1 ratio, UC (n = 35) to CD (n = 19). The molecular and serological features of IBD-U at the end of follow-up were very similar to UC and very different from CD. There was less likelihood of receiving anti-TNFα agents if the diagnosis was IBD-U compared with CD (P < 0.0001). Conclusions: In our cohort, 60% of the IBD-U subjects remained as unclassified at 2 years; of those subsequently classified, a higher percentage followed a course more similar to UC. Most of the IBD-U subjects at diagnosis had serological and molecular signatures that are very similar to UC. Although the atypical presentations made the clinician to make an interim diagnosis of IBD-U, results of the molecular and serological factors performed at the time of diagnosis suggests that they were very similar to UC. However, long-term studies are needed to better understand the natural history and molecular characterization of pediatric onset IBD-U.

AB - Background: Inflammatory bowel disease (IBD) mainly consists of Crohn's disease (CD) and ulcerative colitis (UC). About 10%-15% of patients with IBD cannot be firmly diagnosed with CD or UC; hence, they are initially diagnosed as inflammatory bowel disease unclassified (IBD-U). Having a firm diagnosis is clearly preferred to guide treatment choices, and better understanding of the nature of IBD-U is required. Methods: We performed an analysis of a subset of pediatric subjects from an inception IBD cohort of patients initially enrolled in a prospective multicenter study (the RISK study). Initial diagnosis and 2-year follow-up data from the subjects diagnosed with IBD-U were analyzed. An expert panel verified final diagnosis using predefined criteria as a guide. Serological and disease-relevant ileal and rectal tissue gene expression profiles were investigated. The use and the time to initiate anti-TNFα treatment was analyzed among the outcome groups. Results: A total of 1411 subjects were enrolled with initial diagnosis of IBD, and among them, 136 subjects were initially diagnosed as IBD-U at enrollment. And 26% were reclassified as UC and 14% as CD within 2 years of diagnosis, while 60% remained as IBD-U. Of those who were reclassified, there was a 2:1 ratio, UC (n = 35) to CD (n = 19). The molecular and serological features of IBD-U at the end of follow-up were very similar to UC and very different from CD. There was less likelihood of receiving anti-TNFα agents if the diagnosis was IBD-U compared with CD (P < 0.0001). Conclusions: In our cohort, 60% of the IBD-U subjects remained as unclassified at 2 years; of those subsequently classified, a higher percentage followed a course more similar to UC. Most of the IBD-U subjects at diagnosis had serological and molecular signatures that are very similar to UC. Although the atypical presentations made the clinician to make an interim diagnosis of IBD-U, results of the molecular and serological factors performed at the time of diagnosis suggests that they were very similar to UC. However, long-term studies are needed to better understand the natural history and molecular characterization of pediatric onset IBD-U.

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