Serologic antibodies in relation to outcome in postoperative Crohn's disease

Amy L Hamilton; Michael A Kamm; Peter De Cruz; Emily K Wright; Fabiyola Selvaraj; Fred Princen; Alexandra Gorelik; Danny Liew; Ian C Lawrance; Jane M Andrews; Peter A Bampton; Miles P Sparrow; Timothy H Florin; Peter R Gibson; Henry Debinski; Richard B Gearry; Finlay A Macrae; Rupert W Leong; Ian Kronborg; Graham Radford-Smith; Warwick Selby; Sally J Bell; Steven J Brown; William R Connell

doi:10.1111/jgh.13677

Serologic antibodies in relation to outcome in postoperative Crohn's disease

J Gastroenterol Hepatol. 2017 Jun;32(6):1195-1203. doi: 10.1111/jgh.13677.

Authors

Amy L Hamilton^{1

2}, Michael A Kamm^{1

2}, Peter De Cruz^{1

2

3}, Emily K Wright^{1

2}, Fabiyola Selvaraj⁴, Fred Princen⁴, Alexandra Gorelik⁵, Danny Liew⁶, Ian C Lawrance^{7

8

9

10}, Jane M Andrews^{11

12}, Peter A Bampton¹³, Miles P Sparrow¹⁴, Timothy H Florin^{15

16}, Peter R Gibson^{14

17}, Henry Debinski¹⁸, Richard B Gearry¹⁹, Finlay A Macrae^{20

21}, Rupert W Leong²², Ian Kronborg²³, Graham Radford-Smith^{24

25}, Warwick Selby²⁶, Sally J Bell^{1

2}, Steven J Brown¹, William R Connell¹

Affiliations

¹ Department of Gastroenterology, St Vincent's Hospital, Melbourne, Victoria, Australia.
² Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia.
³ Austin Health, Melbourne, Victoria, Australia.
⁴ Prometheus Laboratories, San Diego, California, USA.
⁵ Melbourne EpiCentre, University of Melbourne and Melbourne Health, Melbourne, Victoria, Australia.
⁶ Department of Epidemiology and Preventative Medicine, Monash University, Melbourne, Victoria, Australia.
⁷ School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia.
⁸ Centre for Inflammatory Bowel Diseases, Saint John of God Hospital, Subiaco, Western Australia, Australia.
⁹ Harry Perkins Institute for Medical Research, Nedlands, Western Australia, Australia.
¹⁰ Fiona Stanley Hospital, Perth, Western Australia, Australia.
¹¹ Department of Gastroenterology and Hepatology, University of Adelaide, Adelaide, South Australia, Australia.
¹² Royal Adelaide Hospital, Adelaide, South Australia, Australia.
¹³ Department of Gastroenterology and Hepatology, Flinders Medical Centre and Flinders University, Adelaide, South Australia, Australia.
¹⁴ Department of Gastroenterology, Alfred Health, Melbourne, Victoria, Australia.
¹⁵ Immunity Infection and Inflammation Program, Mater Research Institute-University of Queensland, and School of Medicine, University of Queensland, Brisbane, Queensland, Australia.
¹⁶ Translational Research Institute, Woolloongabba, Queensland, Australia.
¹⁷ Department of Gastroenterology, Monash University, Melbourne, Victoria, Australia.
¹⁸ Melbourne Gastrointestinal Investigation Unit, Cabrini Hospital, Melbourne, Victoria, Australia.
¹⁹ Department of Medicine, University of Otago, Christchurch, New Zealand.
²⁰ Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia.
²¹ Department of Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
²² Gastroenterology and Liver Services, Concord and Bankstown Hospitals and University of New South Wales, Sydney, New South Wales, Australia.
²³ Department of Gastroenterology, Western Hospital, Melbourne, Victoria, Australia.
²⁴ Department of Gastroenterology, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
²⁵ IBD Group Queensland Institute of Medical Research, University of Queensland, Brisbane, Queensland, Australia.
²⁶ AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.

PMID: 27976801
DOI: 10.1111/jgh.13677

Abstract

Background and aim: Disease recurs frequently after Crohn's disease resection. The role of serological antimicrobial antibodies in predicting recurrence or as a marker of recurrence has not been well defined.

Methods: A total of 169 patients (523 samples) were prospectively studied, with testing peri-operatively, and 6, 12 and 18 months postoperatively. Colonoscopy was performed at 18 months postoperatively. Serologic antibody presence (perinuclear anti-neutrophil cytoplasmic antibody [pANCA], anti-Saccharomyces cerevisiae antibodies [ASCA] IgA/IgG, anti-OmpC, anti-CBir1, anti-A4-Fla2, anti-Fla-X) and titer were tested. Quartile sum score (range 6-24), logistic regression analysis, and correlation with phenotype, smoking status, and endoscopic outcome were assessed.

Results: Patients with ≥ 2 previous resections were more likely to be anti-OmpC positive (94% vs 55%, ≥ 2 vs < 2, P = 0.001). Recurrence at 18 months was associated with anti-Fla-X positivity at baseline (49% vs 29%; positive vs negative, P = 0.033) and 12 months (52% vs 31%, P = 0.04). Patients positive (n = 28) for all four antibacterial antibodies (anti-CBir1, anti-OmpC, anti-A4-Fla2, and anti-Fla-X) at baseline were more likely to experience recurrence at 18 months than patients negative (n = 32) for all four antibodies (82% vs 18%, P = 0.034; odds ratio 6.4, 95% confidence interval 1.16-34.9). The baseline quartile sum score for all six antimicrobial antibodies was higher in patients with severe recurrence (Rutgeert's i3-i4) at 18 months, adjusted for clinical risk factors (odds ratio 1.16, 95% confidence interval 1.01-1.34, P = 0.039). Smoking affected antibody status.

Conclusions: Anti-Fla-X and presence of all anti-bacterial antibodies identifies patients at higher risk of early postoperative Crohn's disease recurrence. Serologic screening pre-operatively may help identify patients at increased risk of recurrence.

Keywords: Crohn's disease; antibodies; postoperative; serology; smoking.

MeSH terms

Adult
Antibodies, Antineutrophil Cytoplasmic / blood
Antibodies, Bacterial / blood
Biomarkers / blood
Colonoscopy
Crohn Disease / diagnosis*
Crohn Disease / surgery*
Female
Humans
Immunoglobulin A / blood
Immunoglobulin G / blood
Male
Middle Aged
Multicenter Studies as Topic
Perioperative Period
Porins / immunology
Prospective Studies
Randomized Controlled Trials as Topic
Recurrence
Risk
Saccharomyces cerevisiae / immunology
Smoking / adverse effects

Substances

Antibodies, Antineutrophil Cytoplasmic
Antibodies, Bacterial
Biomarkers
Immunoglobulin A
Immunoglobulin G
OmpC protein
Porins