Perianal Crohn's disease is associated with distal colonic disease, stricturing disease behavior, IBD-associated serologies and genetic variation in the JAK-STAT pathway

Manreet Kaur; Deepa Panikkath; Xiaofei Yan; Zhenqiu Liu; Dror Berel; Dalin Li; Eric A. Vasiliauskas; Andrew Ippoliti; Marla Dubinsky; David Q. Shih; Gil Y. Melmed; Talin Haritunians; Phillip Fleshner; Stephan R. Targan; Dermot P.B. McGovern

doi:10.1097/MIB.0000000000000705

Perianal Crohn's disease is associated with distal colonic disease, stricturing disease behavior, IBD-associated serologies and genetic variation in the JAK-STAT pathway

Manreet Kaur, Deepa Panikkath, Xiaofei Yan, Zhenqiu Liu, Dror Berel, Dalin Li, Eric A. Vasiliauskas, Andrew Ippoliti, Marla Dubinsky, David Q. Shih, Gil Y. Melmed, Talin Haritunians, Phillip Fleshner, Stephan R. Targan, Dermot P.B. McGovern

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Abstract

Background: Perianal Crohn's Disease (pCD) is a particularly severe phenotype associated with poor quality of life with a reported prevalence of 12%-40%. Previous studies investigating the etiology of pCD have been limited in the numbers of subjects and the intensity of genotyping. The aim of this study was to identify clinical, serological, and genetic factors associated with pCD. Methods: We performed a case-control study comparing patients with (pCD+) and without perianal (pCD -) involvement in CD; defined as the presence of perianal abscesses or fistulae. Data on demographics and clinical features were obtained by chart review. Inflammatory bowel disease-related serology was determined by enzyme-linked immunosorbent assay. Genetic data were generated using Illumina genotyping platforms. Results: We included 1721 patients with CD of which 524 (30.4%) were pCD+ and 1197 were pPCD -. pCD was associated with distal colonic disease (Odds ratio 5.54 [3.23-9.52], P < 0.001), stricturing disease behavior (1.44 [1.14-1.81], P 0.002) and family history of inflammatory bowel disease (4.98 [3.30-7.46], P < 0.001). pCD was associated with higher anti-sacharomyces cerevisae antibodies IgA (P < 0.001) and OmpC (P 0.008) antibody levels. pCD was associated with known inflammatory bowel disease loci, including KIF3B, CRTC3, TRAF3IP2, JAZF1, NRIP1, MST1, FUT2, and PTGER (all P < 0.05). We also identified genetic association with genes involved in autophagy (DAPK1, P 5.11 × 10 -5), TNF alpha pathways (NUCB2, P 8.68 × 10 -5; DAPK1), IFNg pathways (DAPK1; NDFIP2, P 8.74 × 10 -5), and extracellular matrix and scaffolding proteins (USH1C, P 8.68 × 10 -5; NDFIP2; TMC07, P 8.87 × 10 -5). Pathway analyses implicated the JAK-Stat pathway (p c 3.72 × 10 -5). Conclusion: We have identified associations between pCD, more distal colonic inflammation, Crohn's disease-associated serologies, and genetic variation in the JAK-Stat pathway.

Original language	English (US)
Pages (from-to)	862-869
Number of pages	8
Journal	Inflammatory bowel diseases
Volume	22
Issue number	4
DOIs	https://doi.org/10.1097/MIB.0000000000000705
State	Published - Mar 9 2016

All Science Journal Classification (ASJC) codes

Immunology and Allergy
Gastroenterology

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10.1097/MIB.0000000000000705

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Kaur, M., Panikkath, D., Yan, X., Liu, Z., Berel, D., Li, D., Vasiliauskas, E. A., Ippoliti, A., Dubinsky, M., Shih, D. Q., Melmed, G. Y., Haritunians, T., Fleshner, P., Targan, S. R., & McGovern, D. P. B. (2016). Perianal Crohn's disease is associated with distal colonic disease, stricturing disease behavior, IBD-associated serologies and genetic variation in the JAK-STAT pathway. Inflammatory bowel diseases, 22(4), 862-869. https://doi.org/10.1097/MIB.0000000000000705

@article{cc45ccd6128d44d7844a9123bf5430b6,

title = "Perianal Crohn's disease is associated with distal colonic disease, stricturing disease behavior, IBD-associated serologies and genetic variation in the JAK-STAT pathway",

abstract = "Background: Perianal Crohn's Disease (pCD) is a particularly severe phenotype associated with poor quality of life with a reported prevalence of 12%-40%. Previous studies investigating the etiology of pCD have been limited in the numbers of subjects and the intensity of genotyping. The aim of this study was to identify clinical, serological, and genetic factors associated with pCD. Methods: We performed a case-control study comparing patients with (pCD+) and without perianal (pCD -) involvement in CD; defined as the presence of perianal abscesses or fistulae. Data on demographics and clinical features were obtained by chart review. Inflammatory bowel disease-related serology was determined by enzyme-linked immunosorbent assay. Genetic data were generated using Illumina genotyping platforms. Results: We included 1721 patients with CD of which 524 (30.4%) were pCD+ and 1197 were pPCD -. pCD was associated with distal colonic disease (Odds ratio 5.54 [3.23-9.52], P < 0.001), stricturing disease behavior (1.44 [1.14-1.81], P 0.002) and family history of inflammatory bowel disease (4.98 [3.30-7.46], P < 0.001). pCD was associated with higher anti-sacharomyces cerevisae antibodies IgA (P < 0.001) and OmpC (P 0.008) antibody levels. pCD was associated with known inflammatory bowel disease loci, including KIF3B, CRTC3, TRAF3IP2, JAZF1, NRIP1, MST1, FUT2, and PTGER (all P < 0.05). We also identified genetic association with genes involved in autophagy (DAPK1, P 5.11 × 10 -5), TNF alpha pathways (NUCB2, P 8.68 × 10 -5; DAPK1), IFNg pathways (DAPK1; NDFIP2, P 8.74 × 10 -5), and extracellular matrix and scaffolding proteins (USH1C, P 8.68 × 10 -5; NDFIP2; TMC07, P 8.87 × 10 -5). Pathway analyses implicated the JAK-Stat pathway (p c 3.72 × 10 -5). Conclusion: We have identified associations between pCD, more distal colonic inflammation, Crohn's disease-associated serologies, and genetic variation in the JAK-Stat pathway.",

author = "Manreet Kaur and Deepa Panikkath and Xiaofei Yan and Zhenqiu Liu and Dror Berel and Dalin Li and Vasiliauskas, {Eric A.} and Andrew Ippoliti and Marla Dubinsky and Shih, {David Q.} and Melmed, {Gil Y.} and Talin Haritunians and Phillip Fleshner and Targan, {Stephan R.} and McGovern, {Dermot P.B.}",

note = "Publisher Copyright: {\textcopyright} 2016 Crohn's & Colitis Foundation of America, Inc.",

year = "2016",

month = mar,

day = "9",

doi = "10.1097/MIB.0000000000000705",

language = "English (US)",

volume = "22",

pages = "862--869",

journal = "Inflammatory bowel diseases",

issn = "1078-0998",

publisher = "Oxford University Press",

number = "4",

}

Kaur, M, Panikkath, D, Yan, X, Liu, Z, Berel, D, Li, D, Vasiliauskas, EA, Ippoliti, A, Dubinsky, M, Shih, DQ, Melmed, GY, Haritunians, T, Fleshner, P, Targan, SR & McGovern, DPB 2016, 'Perianal Crohn's disease is associated with distal colonic disease, stricturing disease behavior, IBD-associated serologies and genetic variation in the JAK-STAT pathway', Inflammatory bowel diseases, vol. 22, no. 4, pp. 862-869. https://doi.org/10.1097/MIB.0000000000000705

TY - JOUR

T1 - Perianal Crohn's disease is associated with distal colonic disease, stricturing disease behavior, IBD-associated serologies and genetic variation in the JAK-STAT pathway

AU - Kaur, Manreet

AU - Panikkath, Deepa

AU - Yan, Xiaofei

AU - Liu, Zhenqiu

AU - Berel, Dror

AU - Li, Dalin

AU - Vasiliauskas, Eric A.

AU - Ippoliti, Andrew

AU - Dubinsky, Marla

AU - Shih, David Q.

AU - Melmed, Gil Y.

AU - Haritunians, Talin

AU - Fleshner, Phillip

AU - Targan, Stephan R.

AU - McGovern, Dermot P.B.

PY - 2016/3/9

Y1 - 2016/3/9

N2 - Background: Perianal Crohn's Disease (pCD) is a particularly severe phenotype associated with poor quality of life with a reported prevalence of 12%-40%. Previous studies investigating the etiology of pCD have been limited in the numbers of subjects and the intensity of genotyping. The aim of this study was to identify clinical, serological, and genetic factors associated with pCD. Methods: We performed a case-control study comparing patients with (pCD+) and without perianal (pCD -) involvement in CD; defined as the presence of perianal abscesses or fistulae. Data on demographics and clinical features were obtained by chart review. Inflammatory bowel disease-related serology was determined by enzyme-linked immunosorbent assay. Genetic data were generated using Illumina genotyping platforms. Results: We included 1721 patients with CD of which 524 (30.4%) were pCD+ and 1197 were pPCD -. pCD was associated with distal colonic disease (Odds ratio 5.54 [3.23-9.52], P < 0.001), stricturing disease behavior (1.44 [1.14-1.81], P 0.002) and family history of inflammatory bowel disease (4.98 [3.30-7.46], P < 0.001). pCD was associated with higher anti-sacharomyces cerevisae antibodies IgA (P < 0.001) and OmpC (P 0.008) antibody levels. pCD was associated with known inflammatory bowel disease loci, including KIF3B, CRTC3, TRAF3IP2, JAZF1, NRIP1, MST1, FUT2, and PTGER (all P < 0.05). We also identified genetic association with genes involved in autophagy (DAPK1, P 5.11 × 10 -5), TNF alpha pathways (NUCB2, P 8.68 × 10 -5; DAPK1), IFNg pathways (DAPK1; NDFIP2, P 8.74 × 10 -5), and extracellular matrix and scaffolding proteins (USH1C, P 8.68 × 10 -5; NDFIP2; TMC07, P 8.87 × 10 -5). Pathway analyses implicated the JAK-Stat pathway (p c 3.72 × 10 -5). Conclusion: We have identified associations between pCD, more distal colonic inflammation, Crohn's disease-associated serologies, and genetic variation in the JAK-Stat pathway.

AB - Background: Perianal Crohn's Disease (pCD) is a particularly severe phenotype associated with poor quality of life with a reported prevalence of 12%-40%. Previous studies investigating the etiology of pCD have been limited in the numbers of subjects and the intensity of genotyping. The aim of this study was to identify clinical, serological, and genetic factors associated with pCD. Methods: We performed a case-control study comparing patients with (pCD+) and without perianal (pCD -) involvement in CD; defined as the presence of perianal abscesses or fistulae. Data on demographics and clinical features were obtained by chart review. Inflammatory bowel disease-related serology was determined by enzyme-linked immunosorbent assay. Genetic data were generated using Illumina genotyping platforms. Results: We included 1721 patients with CD of which 524 (30.4%) were pCD+ and 1197 were pPCD -. pCD was associated with distal colonic disease (Odds ratio 5.54 [3.23-9.52], P < 0.001), stricturing disease behavior (1.44 [1.14-1.81], P 0.002) and family history of inflammatory bowel disease (4.98 [3.30-7.46], P < 0.001). pCD was associated with higher anti-sacharomyces cerevisae antibodies IgA (P < 0.001) and OmpC (P 0.008) antibody levels. pCD was associated with known inflammatory bowel disease loci, including KIF3B, CRTC3, TRAF3IP2, JAZF1, NRIP1, MST1, FUT2, and PTGER (all P < 0.05). We also identified genetic association with genes involved in autophagy (DAPK1, P 5.11 × 10 -5), TNF alpha pathways (NUCB2, P 8.68 × 10 -5; DAPK1), IFNg pathways (DAPK1; NDFIP2, P 8.74 × 10 -5), and extracellular matrix and scaffolding proteins (USH1C, P 8.68 × 10 -5; NDFIP2; TMC07, P 8.87 × 10 -5). Pathway analyses implicated the JAK-Stat pathway (p c 3.72 × 10 -5). Conclusion: We have identified associations between pCD, more distal colonic inflammation, Crohn's disease-associated serologies, and genetic variation in the JAK-Stat pathway.

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U2 - 10.1097/MIB.0000000000000705

DO - 10.1097/MIB.0000000000000705

M3 - Article

C2 - 26937622

AN - SCOPUS:84962247996

SN - 1078-0998

VL - 22

SP - 862

EP - 869

JO - Inflammatory bowel diseases

JF - Inflammatory bowel diseases

IS - 4

ER -

Perianal Crohn's disease is associated with distal colonic disease, stricturing disease behavior, IBD-associated serologies and genetic variation in the JAK-STAT pathway

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