NOD2/CARD15 Mutations correlate with severe pouchitis after ileal pouch-anal anastomosis

Rishabh Sehgal, Arthur Berg, John P. Hegarty, Ashley A. Kelly, Zhenwu Lin, Lisa Poritz, Walter Koltun

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

PURPOSE: Pouchitis and Crohn's-like complications can plague patients after IPAA. NOD2 is an intracellular sensor for bacterial cell wall peptidoglycan. NOD2 mutations compromise host response to enteric bacteria and are increased in Crohn's disease. We hypothesize that IPAA patients with complications (Crohn's diseaselike/pouchitis) have a higher rate of NOD2 mutations compared with asymptomatic IPAA patients. METHODS: Patients were retrospectively subclassified into the following groups: 1) IPAA with Crohn's-like complications (n = 28, perianal fistula, pouch inlet stricture/upstream small-bowel disease, or biopsies showing granulomata) occurring at least 6 months after ileostomy closure; 2) IPAA with mild pouchitis (n = 33, ≤3 episodes/y for 2 consecutive years); 3) IPAA with severe pouchitis (n = 9, ≥4 episodes/y for 2 consecutive years or need for continuous antibiotics); 4) IPAA without complications or pouchitis (n = 37); 5) patients with Crohn's disease with colitis undergoing total proctocolectomy/ileostomy (n = 11); and 6) healthy controls (n = 269). The 3 NOD2 single-nucleotide polymorphism mutations (rs2066844, rs2066845, and rs2066847) previously identified as associated with Crohn's disease were genotyped using polymerase chain reaction. Groups were compared by use of x2 with Yates continuity correction. RESULTS: NOD2 mutations were found in 8.5% of healthy controls. NOD2 mutations were significantly higher in the severe pouchitis group (67%) compared with both asymptomatic IPAA (5.4%, P < .001) and IPAA with Crohn's disease-like complications (14.3%, P = .008) groups. CONCLUSIONS: 1) Asymptomatic IPAA patients have a low incidence of NOD2 mutations not significantly different from patients with mild pouchitis or healthy controls. 2) Patients with severe pouchitis had the highest incidence of NOD2 mutations, suggesting that this group may have a compromised host defense mechanism to enteric bacteria. 3) Patients with Crohn's-like complications after IPAA have a significantly lower incidence of NOD2 mutations than patients with severe pouchitis, suggesting a different genetic makeup in these 2 patient groups. Preoperative assessment of NOD2 in the equivocal IPAA candidate may predict severe pouchitis and might assist in preoperative surgical decision making.

Original languageEnglish (US)
Pages (from-to)1487-1494
Number of pages8
JournalDiseases of the colon and rectum
Volume53
Issue number11
DOIs
StatePublished - Nov 1 2010

Fingerprint

Pouchitis
Colonic Pouches
Mutation
Crohn Disease
Ileostomy
Enterobacteriaceae
Incidence
Plague
Peptidoglycan
Defense Mechanisms
Mutation Rate
Colitis
Granuloma
Cell Wall
Fistula
Single Nucleotide Polymorphism
Decision Making
Pathologic Constriction

All Science Journal Classification (ASJC) codes

  • Gastroenterology

Cite this

Sehgal, Rishabh ; Berg, Arthur ; Hegarty, John P. ; Kelly, Ashley A. ; Lin, Zhenwu ; Poritz, Lisa ; Koltun, Walter. / NOD2/CARD15 Mutations correlate with severe pouchitis after ileal pouch-anal anastomosis. In: Diseases of the colon and rectum. 2010 ; Vol. 53, No. 11. pp. 1487-1494.
@article{00f6f259baaa4e4185481abc94b69ec0,
title = "NOD2/CARD15 Mutations correlate with severe pouchitis after ileal pouch-anal anastomosis",
abstract = "PURPOSE: Pouchitis and Crohn's-like complications can plague patients after IPAA. NOD2 is an intracellular sensor for bacterial cell wall peptidoglycan. NOD2 mutations compromise host response to enteric bacteria and are increased in Crohn's disease. We hypothesize that IPAA patients with complications (Crohn's diseaselike/pouchitis) have a higher rate of NOD2 mutations compared with asymptomatic IPAA patients. METHODS: Patients were retrospectively subclassified into the following groups: 1) IPAA with Crohn's-like complications (n = 28, perianal fistula, pouch inlet stricture/upstream small-bowel disease, or biopsies showing granulomata) occurring at least 6 months after ileostomy closure; 2) IPAA with mild pouchitis (n = 33, ≤3 episodes/y for 2 consecutive years); 3) IPAA with severe pouchitis (n = 9, ≥4 episodes/y for 2 consecutive years or need for continuous antibiotics); 4) IPAA without complications or pouchitis (n = 37); 5) patients with Crohn's disease with colitis undergoing total proctocolectomy/ileostomy (n = 11); and 6) healthy controls (n = 269). The 3 NOD2 single-nucleotide polymorphism mutations (rs2066844, rs2066845, and rs2066847) previously identified as associated with Crohn's disease were genotyped using polymerase chain reaction. Groups were compared by use of x2 with Yates continuity correction. RESULTS: NOD2 mutations were found in 8.5{\%} of healthy controls. NOD2 mutations were significantly higher in the severe pouchitis group (67{\%}) compared with both asymptomatic IPAA (5.4{\%}, P < .001) and IPAA with Crohn's disease-like complications (14.3{\%}, P = .008) groups. CONCLUSIONS: 1) Asymptomatic IPAA patients have a low incidence of NOD2 mutations not significantly different from patients with mild pouchitis or healthy controls. 2) Patients with severe pouchitis had the highest incidence of NOD2 mutations, suggesting that this group may have a compromised host defense mechanism to enteric bacteria. 3) Patients with Crohn's-like complications after IPAA have a significantly lower incidence of NOD2 mutations than patients with severe pouchitis, suggesting a different genetic makeup in these 2 patient groups. Preoperative assessment of NOD2 in the equivocal IPAA candidate may predict severe pouchitis and might assist in preoperative surgical decision making.",
author = "Rishabh Sehgal and Arthur Berg and Hegarty, {John P.} and Kelly, {Ashley A.} and Zhenwu Lin and Lisa Poritz and Walter Koltun",
year = "2010",
month = "11",
day = "1",
doi = "10.1007/DCR.0b013e3181f22635",
language = "English (US)",
volume = "53",
pages = "1487--1494",
journal = "Diseases of the Colon and Rectum",
issn = "0012-3706",
publisher = "Lippincott Williams and Wilkins",
number = "11",

}

NOD2/CARD15 Mutations correlate with severe pouchitis after ileal pouch-anal anastomosis. / Sehgal, Rishabh; Berg, Arthur; Hegarty, John P.; Kelly, Ashley A.; Lin, Zhenwu; Poritz, Lisa; Koltun, Walter.

In: Diseases of the colon and rectum, Vol. 53, No. 11, 01.11.2010, p. 1487-1494.

Research output: Contribution to journalArticle

TY - JOUR

T1 - NOD2/CARD15 Mutations correlate with severe pouchitis after ileal pouch-anal anastomosis

AU - Sehgal, Rishabh

AU - Berg, Arthur

AU - Hegarty, John P.

AU - Kelly, Ashley A.

AU - Lin, Zhenwu

AU - Poritz, Lisa

AU - Koltun, Walter

PY - 2010/11/1

Y1 - 2010/11/1

N2 - PURPOSE: Pouchitis and Crohn's-like complications can plague patients after IPAA. NOD2 is an intracellular sensor for bacterial cell wall peptidoglycan. NOD2 mutations compromise host response to enteric bacteria and are increased in Crohn's disease. We hypothesize that IPAA patients with complications (Crohn's diseaselike/pouchitis) have a higher rate of NOD2 mutations compared with asymptomatic IPAA patients. METHODS: Patients were retrospectively subclassified into the following groups: 1) IPAA with Crohn's-like complications (n = 28, perianal fistula, pouch inlet stricture/upstream small-bowel disease, or biopsies showing granulomata) occurring at least 6 months after ileostomy closure; 2) IPAA with mild pouchitis (n = 33, ≤3 episodes/y for 2 consecutive years); 3) IPAA with severe pouchitis (n = 9, ≥4 episodes/y for 2 consecutive years or need for continuous antibiotics); 4) IPAA without complications or pouchitis (n = 37); 5) patients with Crohn's disease with colitis undergoing total proctocolectomy/ileostomy (n = 11); and 6) healthy controls (n = 269). The 3 NOD2 single-nucleotide polymorphism mutations (rs2066844, rs2066845, and rs2066847) previously identified as associated with Crohn's disease were genotyped using polymerase chain reaction. Groups were compared by use of x2 with Yates continuity correction. RESULTS: NOD2 mutations were found in 8.5% of healthy controls. NOD2 mutations were significantly higher in the severe pouchitis group (67%) compared with both asymptomatic IPAA (5.4%, P < .001) and IPAA with Crohn's disease-like complications (14.3%, P = .008) groups. CONCLUSIONS: 1) Asymptomatic IPAA patients have a low incidence of NOD2 mutations not significantly different from patients with mild pouchitis or healthy controls. 2) Patients with severe pouchitis had the highest incidence of NOD2 mutations, suggesting that this group may have a compromised host defense mechanism to enteric bacteria. 3) Patients with Crohn's-like complications after IPAA have a significantly lower incidence of NOD2 mutations than patients with severe pouchitis, suggesting a different genetic makeup in these 2 patient groups. Preoperative assessment of NOD2 in the equivocal IPAA candidate may predict severe pouchitis and might assist in preoperative surgical decision making.

AB - PURPOSE: Pouchitis and Crohn's-like complications can plague patients after IPAA. NOD2 is an intracellular sensor for bacterial cell wall peptidoglycan. NOD2 mutations compromise host response to enteric bacteria and are increased in Crohn's disease. We hypothesize that IPAA patients with complications (Crohn's diseaselike/pouchitis) have a higher rate of NOD2 mutations compared with asymptomatic IPAA patients. METHODS: Patients were retrospectively subclassified into the following groups: 1) IPAA with Crohn's-like complications (n = 28, perianal fistula, pouch inlet stricture/upstream small-bowel disease, or biopsies showing granulomata) occurring at least 6 months after ileostomy closure; 2) IPAA with mild pouchitis (n = 33, ≤3 episodes/y for 2 consecutive years); 3) IPAA with severe pouchitis (n = 9, ≥4 episodes/y for 2 consecutive years or need for continuous antibiotics); 4) IPAA without complications or pouchitis (n = 37); 5) patients with Crohn's disease with colitis undergoing total proctocolectomy/ileostomy (n = 11); and 6) healthy controls (n = 269). The 3 NOD2 single-nucleotide polymorphism mutations (rs2066844, rs2066845, and rs2066847) previously identified as associated with Crohn's disease were genotyped using polymerase chain reaction. Groups were compared by use of x2 with Yates continuity correction. RESULTS: NOD2 mutations were found in 8.5% of healthy controls. NOD2 mutations were significantly higher in the severe pouchitis group (67%) compared with both asymptomatic IPAA (5.4%, P < .001) and IPAA with Crohn's disease-like complications (14.3%, P = .008) groups. CONCLUSIONS: 1) Asymptomatic IPAA patients have a low incidence of NOD2 mutations not significantly different from patients with mild pouchitis or healthy controls. 2) Patients with severe pouchitis had the highest incidence of NOD2 mutations, suggesting that this group may have a compromised host defense mechanism to enteric bacteria. 3) Patients with Crohn's-like complications after IPAA have a significantly lower incidence of NOD2 mutations than patients with severe pouchitis, suggesting a different genetic makeup in these 2 patient groups. Preoperative assessment of NOD2 in the equivocal IPAA candidate may predict severe pouchitis and might assist in preoperative surgical decision making.

UR - http://www.scopus.com/inward/record.url?scp=78349269077&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78349269077&partnerID=8YFLogxK

U2 - 10.1007/DCR.0b013e3181f22635

DO - 10.1007/DCR.0b013e3181f22635

M3 - Article

VL - 53

SP - 1487

EP - 1494

JO - Diseases of the Colon and Rectum

JF - Diseases of the Colon and Rectum

SN - 0012-3706

IS - 11

ER -