Matrix gla protein, a potential marker of tissue remodelling and physiological ageing of the gut in crohn’s disease

Abstract

Background

The inactive dephosphorylated and uncarboxylated form of the matrix Gla protein (dp-ucMGP) has been shown to be increased in plasma of inflammatory bowel disease (IBD) patients. Our aim was to assess if the plasmatic level of dp-ucMGP could reflect disease endoscopic activity, presence of strictures and cumulative structural bowel damage in Crohn’s disease (CD) patients.

Methods

The plasmatic level of dp-ucMGP was measured in a monocentric cohort of prospectively recruited patients. The analysis was done by chemiluminescent immunoassay on blood samples collected the day of a planned ileocolonoscopy. In addition to classical clinical data (gender, age, body mass index (BMI), disease duration, current treatment), endoscopic data (disease location, Crohn’s Disease Endoscopic Index of Severity (CDEIS), mucosal healing (MH), presence of 9 CD lesion types) and biological markers (faecal calprotectin and C-reactive protein (CRP)) were collected. The association between dp-ucMGP level and Lémann index was also investigated. Univariate linear regression was used to investigate the relationship between dp-ucMGP level and different parameters collected.

Results

A total of 82 ileocolonoscopies and dp-ucMGP assays were performed in 75 CD patients (45 females; 37 ileocolonic, 19 ileal and 19 colonic diseases) between October 2012 and November 2019. A total of 24 patients (29.3%) showed MH. The dp-ucMGP levels were not associated with MH, CDEIS, faecal calprotectin or CRP levels. Plasmatic dp-ucMGP levels increased significantly with age (p = 0.0032), disease duration (p = 0.0033), corticosteroids use (p = 0.019) and tended to increase in patients with intestinal strictures (p = 0.086) but not with the Lémann index.

Conclusion

The significant increase of plasmatic dp-ucMGP levels with age, disease duration and the trend observed in patients with non-ulcerated strictures may suggest that this extracellular matrix protein could be a marker of tissue remodelling and physiological ageing of the gut.

Keywords:

• dp-ucMGP
• crohn’s disease
• tissue remodelling
• physiological ageing
• intestinal fibrosis

Author contributions

PD, EC, and EL conceive the study. SV collected clinical data and wrote the article. RG protocolled MRIs. LS performed statistical analyses. RG, PD, LS, EB, CS, MAM, CM, NP, PM, EC and EL critically reviewed the content of the paper. The manuscript was approved by all authors.

Disclosure statement

S Vieujean: speaker fees from Ferring, Janssen, Abbvie and Takeda. P Delanaye has served as consultant for iDS. E Cavalier has served as consultant for iDS. Edouard Louis: Research grant: Janssen, Pfizer, Ferring, Falk, Abbvie and Takeda; educational grant: AbbVie, Janssen, Fresenius-Kabi and Takeda; speaker fees: Abbvie, Falk, Ferring, Janssen, Pfizer, Galapagos and Takeda; advisory board: Abbvie, Celgene, Ferring, Janssen, BMS, Pfizer, and Takeda, Galapagos, Gilead, Arena, Elli Lilly; consultant: Abbvie. R Gillard, L Seidel, E Bequet, C Salée, MA Meuwis, C Massot, N Pierre, P Meunier declares no conflict of interest.

Data availability statement

The data underlying this article are available in the article.

Additional information

Funding

S.V. was financially supported by the National Fund for Scientific Research (F.R.S.-FNRS) [grant number 40001034].