Faecal Myeloperoxidase as a Biomarker of Endoscopic Activity in Inflammatory Bowel Disease

Abstract

Background and aims: Inflammatory bowel disease [IBD], consisting of Crohn's disease [CD] and ulcerative colitis [UC], is a relapsing-remitting illness. Treat-to-target IBD management strategies require monitoring of gastrointestinal inflammation. This study aimed to investigate faecal myeloperoxidase [fMPO], a neutrophil granule enzyme, as a biomarker of IBD activity.

Methods: Prospectively recruited participants with IBD, undergoing ileocolonoscopy for disease assessment, provided biological samples and completed symptom questionnaires prior to endoscopy. fMPO, C-reactive protein [CRP], and faecal calprotectin [fCal] were compared with validated endoscopic indices [simple endoscopic score for CD and UC endoscopic index of severity]. Receiver operating characteristic [ROC] curves assessed the performance of fMPO, CRP, and fCal in predicting endoscopic disease activity. Baseline biomarkers were used to predict a composite endpoint of complicated disease at 12 months [need for escalation of biologic/immunomodulator due to relapse, steroid use, IBD-related hospitalisation, and surgery].

Results: A total of 172 participants were recruited [91 female, 100 with CD]. fMPO was significantly correlated with endoscopic activity in both CD [r = 0.53, p < 0.01] and UC [r = 0.63, p < 0.01], and with fCal in all patients with IBD [r = 0.82, p < 0.01]. fMPO was effective in predicting moderate-to-severely active CD [AUROC 0.86, p < 0.01] and UC [AUROC 0.92, p < 0.01]. Individuals with a baseline fMPO > 26 µg/g were significantly more likely to reach the composite outcome at 12 months (hazard ratio [HR] 3.71, 95% confidence interval [CI] 2.07-6.64, p < 0.01).

Conclusions: Faecal myeloperoxidase is an accurate biomarker of endoscopic activity in IBD and predicted a more complicated IBD course during follow-up.

Keywords: Biomarkers; myeloperoxidase; prognosis.

Graphical abstract

Figure 1.

Correlation between faecal myeloperoxidase [fMPO] protein concentration with fMPO activity using randomly selected stool samples to encompass a range of fMPO protein concentrations; 0-–9 μg/g, 50–199 μg/g, and > 200 μg/g. The correlation was performed on the linear data.

Figure 2.

Correlations between faecal biomarkers and clinical symptoms with endoscopic activity in inflammatory bowel disease.[A] Faecal calprotectin [fCal] and Simple Endoscopic Score for Crohn’s Disease [SES-CD]. [B] fCal and Ulcerative Colitis Endoscopic Index of Severity [UCEIS]; [C] Faecal myeloperoxidase protein [fMPO] and SES-CD. [D] fMPO and UCEIS. [E] SES-CD and Harvey–Bradshaw index [HBI]. [F] UCEIS and Simple Clinical Colitis Activity Index [SCCAI].

Figure 3.

Faecal myeloperoxidase [fMPO] protein was significantly correlated with faecal calprotectin [fCal] in patients with inflammatory bowel disease [A]. fMPO protein differed significantly between individuals in endoscopic remission [SES-CD ≤ 2, UCEIS ≤ 1] and those with moderate [SES-CD 7–15, UCEIS 5–6] or severely active [SES-CD > 15, UCEIS ≥ 7] Crohn’s disease [B] and ulcerative colitis [C]. SES-CD, Simple Endoscopic Score for Crohn’s Disease; UCEIS, Ulcerative Colitis Endoscopic Index of Severity. Mild disease = SES-CD 3–6, UCEIS 2–4. ns = p > 0.05; ***p < 0.001. Correlations for panel A performed on linear biomarker data.

Figure 4

Faecal calprotectin [fCal] and faecal myeloperoxidase [fMPO] protein both predicted moderat- to-severe endoscopic activity in CD [A] and UC [B], in comparison with C-reactive protein [CRP]. CD, Crohn’s disease; UC, ulcerative colitis; AUROC, area under the receiver operating characteristic curve.

Figure 5

Kaplan–Meier Curves showing differences in probability in reaching a composite outcome of escalation of immunomodulator/biologic therapy, corticosteroid use, IBD related hospitalisation, and surgery during 12 months of follow-up based on threshold values of baseline biomarkers [faecal calprotectin, fCal, >250 µg/g<; faecal myeloperoxidase, fMPO, fMPO > 26 µg/g<]. IBD, inflammatory bowel disease.