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
ARTICLE HIGHLIGHTS
Research background

Perianal fistulae are common and cause significant physical and psychosocial morbidity. Current treatments come with a significant failure rate. Idiopathic perianal fistulae are thought to arise from a primary infection of an anal gland, which leads to penetrating suppuration and fistula formation. Crohn’s disease (CD)-related perianal fistulae is thought to arise from altered inflammatory pathways within the mucosa.

Research motivation

The aetiology and pathophysiology of perianal fistulae is still unclear. A better understanding could lead to better treatments. Most research to date has assumed idiopathic and CD-related fistulae to be fundamentally different. However this assumption has never been tested.

Research objectives

We hypothesised that idiopathic and CD-related perianal fistulae are different and aimed to test this systematically by comparing their clinical phenotypes, cytokine and phosphoprotein profiles.

Research methods

We conducted a prospective cohort study within a university hospital. Sixty-one consecutive patients undergoing surgery for perianal fistula were recruited. Clinical data, pre- and post-operative Perineal Disease Activity Index (PDAI) and EQ-5D-5L scores were measured. Biopsies of the fistula tract, granulation tissue, internal opening mucosa and rectal mucosa were obtained at surgery. These were processed in our laboratory to measure 30 cytokines and 39 phosphoproteins. To our knowledge, this is the largest study to date to systematically compare idiopathic and CD-related perianal fistulae in a well-defined patient cohort.

Research results

The PDAI was significantly higher and complex pathoanatomy was more prevalent in the CD group, supporting the commonly-held belief that CD-related perianal fistulae are more severe and complex than idiopathic. IL-12p70 concentration at the internal opening was higher and the IL-1RA/IL-1β ratio was significantly lower at the internal opening in patients with CD. There were no significant differences between the groups for any other cytokine concentrations at the four specimen sites. There were also no significant differences in phosphoprotein levels between the patient groups at any specimen site.

Research conclusions

CD-related perianal fistulae are often clinically more severe and complex. However, they do not substantially differ in their expression of a large panel of cytokines and phosphoproteins.

Research perspectives

Our data contributes to an emerging theory that idiopathic and CD-related perianal fistulae may not be as immunologically distinct as previously supposed. This line of reasoning opens the possibility that biological agents effective in CD-related perianal fistulae may also have a role in selected idiopathic perianal fistulae especially when recent randomised trial data have exposed the general limitations of surgery. Further research is warranted.