Increased remodeling of type XXII collagen is associated with an inflammatory phenotype in Crohn’s disease.
Abstract
In Crohn’s disease, extracellular matrix (ECM) dysfunction and loss of tissue integrity are key pathological features. Fibril-associated collagens with interrupted triple helices (FACIT) are known to regulate ECM assembly and mediate biophysical cues in their microenvironment but remain largely understudied. This study aimed to investigate a novel biomarker reflecting remodelling of the FACIT collagen type XXII (PRO-C22) and explore its association with differing phenotypes of CD and treatment outcomes. Two cohorts of patients with CD were included in the study [cohort 1 (n = 65), cohort 2 (n = 32)]. Baseline serum samples were drawn. After sampling, patients in cohort 2 started treatment with the α4β7 integrin antagonist vedolizumab. Information on treatment continuation beyond 12 months was used as an exploratory surrogate outcome for treatment trajectory. Disease phenotypes were classified according to the Montreal disease behaviour classification. Patients with a luminal CD phenotype had significantly elevated levels of type PRO-C22 compared with patients who had a stricturing disease phenotype. Patients with penetrating disease had elevated levels of PRO-C22 compared with patients with stricturing disease. Patients receiving vedolizumab who had discontinued the use within 12 months from induction had significantly elevated levels of PRO-C22 at baseline, compared with patients who continued the use of vedolizumab beyond 12 months. Our results highlight the potential of PRO-C22 as a biomarker of ongoing inflammatory activity in CD, and suggest a possible association with treatment trajectory in patients with a more progressive disease receiving vedolizumab.
