Observational Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Pathophysiol. Nov 13, 2019; 10(4): 42-53
Published online Nov 13, 2019. doi: 10.4291/wjgp.v10.i4.42
Comparison of cytokine and phosphoprotein profiles in idiopathic and Crohn’s disease-related perianal fistula
James B Haddow, Omar Musbahi, Thomas T MacDonald, Charles H Knowles
James B Haddow, Omar Musbahi, Thomas T MacDonald, Charles H Knowles, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 5AT, United Kingdom
Author contributions: Haddow J MacDonald TT and Knowles CH conceived and designed the study; Haddow J recruited the patients and acquired the data; Haddow J and Knowles CH acquired the specimens; Haddow J and Musbahi O performed the laboratory measurements and inputted the data; Haddow J and Knowles CH analysed the data; Haddow J, Knowles CH and MacDonald TT interpreted the data; Haddow J wrote the article; Haddow J, Musbahi O, MacDonald TT and Knowles CH edited, reviewed and approved the final article.
Supported by Bowel and Cancer Research charity, No. MMBG1J3R.
Institutional review board statement: The study was reviewed and approved by Queen’s Square Research Ethics Committee.
Informed consent statement: Informed consent was obtained from the patients.
Conflict-of-interest statement: The authors have no conflicts of interest.
Data sharing statement: Any researcher wishing to access the data or materials referred to within this paper are welcome to contact the corresponding author.
STROBE statement: The STROBE guidelines were followed for reporting.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: James B Haddow, FRCS, MD, Academic Fellow, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, National Bowel Research Centre, 1st Floor Abernethy Building, 2 Newark St, Whitechapel, London E1 2AT, United Kingdom. james.haddow@icloud.com
Telephone: +44-20-78825555
Received: April 30, 2019
Peer-review started: April 30, 2019
First decision: September 6, 2019
Revised: September 28, 2019
Accepted: October 18, 2019
Article in press: October 18, 2019
Published online: November 13, 2019
Processing time: 196 Days and 5.3 Hours
Abstract
BACKGROUND

Perianal fistulae are either primary (idiopathic) or secondary [commonly associated with Crohn’s disease, (CD)]. It is assumed, although not proven, that the pathophysiology differs.

AIM

To systematically compare the clinical phenotypes, cytokine and phosphoprotein profiles of idiopathic and CD-related perianal fistulae.

METHODS

Sixty-one patients undergoing surgery for perianal fistula were prospectively recruited (48 idiopathic, 13 CD) into a cohort study. Clinical data, including the Perineal Disease Activity Index (PDAI) and EQ-5D-5L were collected. Biopsies of the fistula tract, granulation tissue, internal opening mucosa and rectal mucosa were obtained at surgery. Concentrations of 30 cytokines and 39 phosphoproteins were measured in each biopsy using a magnetic bead multiplexing instrument and a chemiluminescent antibody array respectively. Over 12000 clinical and 23500 laboratory measurements were made.

RESULTS

The PDAI was significantly higher (indicating more active disease) in the CD group with a mean difference of 2.40 (95%CI: 0.52-4.28, P = 0.01). Complex pathoanatomy was more prevalent in the CD group, namely more multiple fistulae, supralevator extensions, collections and rectal thickening. The IL-12p70 concentration at the internal opening specimen site was significantly higher (median difference 19.7 pg/mL, 99%CI: 0.2-40.4, P = 0.008) and the IL-1RA/IL-1β ratio was significantly lower in the CD group at the internal opening specimen site (median difference 15.0, 99%CI = 0.4-50.5, P = 0.008). However in the remaining 27 cytokines and all 39 of the phosphoproteins across the four biopsy sites, no significant differences were found between the groups.

CONCLUSION

CD-related perianal fistulae are more clinically severe and anatomically complex than idiopathic perianal fistulae. However, overall there are no major differences in cytokine and phosphoprotein profiles.

Keywords: Anal fistula; Crohn’s disease; Cytokines; Phosphoproteins; Pathogenesis

Core tip: We systematically compared idiopathic and Crohn’s perianal fistulae, but did not find major differences in their cytokine and phosphoprotein profiles. Although more research is needed, our results support the thesis that biological agents effective in Crohn’s disease-related perianal fistulae may also have a role in selected surgically-intractable idiopathic perianal fistulae.