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P267 Candidate serum markers in newly diagnosed Crohn's disease patients

Smids C.*1, Horjus Talabur Horje C.1, Nierkens S.2, Drylewicz J.3, Groenen M.1, Wahab P.1, van Lochem E.4

1Rijnstate Hospital, IBD Centre, Gastroenterology and Hepatology, Arnhem, Netherlands 2University Medical Centre Utrecht, U-DAIR and Laboratory of Translational Immunology, Utrecht, Netherlands 3University Medical Centre Utrecht, Laboratory of Translational Immunology, Utrecht, Netherlands 4Rijnstate Hospital, Microbiology and Immunology, Arnhem, Netherlands

Background

More than half of patients with Crohn's disease (CD) develop disease complications requiring aggressive medical therapy or surgery over time. However, predicting disease course and treatment response remains difficult. We therefore identified distinctive serum analytes associated with disease activity and course in newly diagnosed, untreated CD patients at presentation and during their follow-up.

Methods

In a pilot study, a multiplex immunoassay analysis on 35 markers was performed on serum from 20 untreated CD patients at the time of primary diagnosis following endoscopic evaluation. The 11 most potent markers (IL-37, CCL-5, CCL-19, CXCL-13, sIL-2R, sIL-6R sTNF-R1, sTNF-R2, S100A8, VCAM, MMP-1), associated with disease activity, phenotype or course, were measured in a consecutive cohort of 66 CD patients at primary diagnosis and during follow-up (n=39). A healthy control group was included (n=20).

Results

Almost all pro-inflammatory cytokines were undetectable at baseline in most of the CD patients in the pilot cohort.

In the consecutive cohort, CD patients had higher baseline levels of sTNF-R2 (p=0.001), sIL-2R (p=0.0001) and MMP-1 (p=0.001) compared to healthy controls.

Serial measurements revealed that sTNF-R2, sIL-2R and MMP-1 levels dropped statistically significant from baseline level when there was remission at follow-up, while they remained high during an exacerbation at follow-up (Fig. 1).

Great decline of sTNF-R1 levels was found during remission with 6.7 fold lower levels than in healthy controls (p=0.015, Fig. 1).

Patients that did not respond to initial prednisone treatment had higher baseline levels of sTNF-R2 (p=0.001).

Patients with relapsing disease (≥1 disease exacerbation during follow-up) had lower baseline sTNF-R2 and VCAM levels compared to patients with long-lasting remission.

Figure 1. Serum analyte levels at baseline and follow-up, followed by log transformation. Levels of the group in remission (blue, n=29) and during exacerbation at follow-up blood collection (red, n=10). Healthy controls in green. *p-value <0.05.

Conclusion

There is a very small window of opportunity for the analysis of early inflammatory processes in CD patients, as therapy that influences the immune system is usually initiated soon after diagnosis. Serial measurements in patients at diagnosis and during follow-up identified sTNF-R1, sTNF-R2, sIL-2R and MMP-1 as potential markers of disease activity. Furthermore, baselinesTNF-R2 was associated with prednisone response and disease course. These candidate markers are easily accessible and implementable in daily practice and therefore warrant further investigation.