Title: Serological assessment of PRO-C16 (type XVI collagen formation) reflects intestinal
fibrostenotic strictures in patients with Crohn’s disease
Version: 4 Date: 30 Jun 2025
Reviewer's report:
I thank the authors for their responses. Please fin below some minor points:
“Based on these findings by Ratzinger et al.[5] and Jensen et al.[24], demonstrating type XVI
collagen’s relevance in patients with UC and the lack of a biomarker for intestinal fibrosis,
especially in CD patients. Therefore, we wanted to investigate PRO-C16 as a marker of intestinal
fibrostenotic strictures in Crohn’s disease patients. “ These last sentences of the introduction are
not well written in my opinion.
-“Even though PRO-C16 did not reach statistical significance between the inactive vs. active
CD patients based on the CDAI score, we still observed numerically elevated PRO-C16 serum
levels in the active group. However, type XVI collagen has been shown to increase the
expression and activation of MMP-9 locally in tissue at the site of insult by immune cells,
e.g., macrophages and neutrophils[31]”. This could explain the elevated levels of PRO-C16
observed in Crohn’s disease patients with active disease, as MMP-9 tissue expression leads
to chronic intestinal mucosal damage[14–20, 32, 33]. This process is thought to be facilitated
by type XVI collagen’s ability to maintain adhesion of intestinal subepithelial myofibroblasts,
thus increasing the pathological development of intestinal fibrostenotic strictures[5]. “These
sentences are highly speculative and not very comprehensible. The link between MMP9 and
PRO-C16 is not explained. I suggest removing this part.
Title: Serological assessment of PRO-C16 (type XVI collagen formation) reflects intestinal
fibrostenotic strictures in patients with Crohn’s disease
Version: 4 Date: 30 Jun 2025
Reviewer's report:
I thank the authors for their responses. Please fin below some minor points:
“Based on these findings by Ratzinger et al.[5] and Jensen et al.[24], demonstrating type XVI
collagen’s relevance in patients with UC and the lack of a biomarker for intestinal fibrosis,
especially in CD patients. Therefore, we wanted to investigate PRO-C16 as a marker of intestinal
fibrostenotic strictures in Crohn’s disease patients. “ These last sentences of the introduction are
not well written in my opinion.
-“Even though PRO-C16 did not reach statistical significance between the inactive vs. active
CD patients based on the CDAI score, we still observed numerically elevated PRO-C16 serum
levels in the active group. However, type XVI collagen has been shown to increase the
expression and activation of MMP-9 locally in tissue at the site of insult by immune cells,
e.g., macrophages and neutrophils[31]”. This could explain the elevated levels of PRO-C16
observed in Crohn’s disease patients with active disease, as MMP-9 tissue expression leads
to chronic intestinal mucosal damage[14–20, 32, 33]. This process is thought to be facilitated
by type XVI collagen’s ability to maintain adhesion of intestinal subepithelial myofibroblasts,
thus increasing the pathological development of intestinal fibrostenotic strictures[5]. “These
sentences are highly speculative and not very comprehensible. The link between MMP9 and
PRO-C16 is not explained. I suggest removing this part.
Please review this paper.
user
Title: Serological assessment of PRO-C16 (type XVI collagen formation) reflects intestinal
fibrostenotic strictures in patients with Crohn’s disease
Version: 4 Date: 30 Jun 2025
Reviewer's report:
I thank the authors for their responses. Please fin below some minor points:
“Based on these findings by Ratzinger et al.[5] and Jensen et al.[24], demonstrating type XVI
collagen’s relevance in patients with UC and the lack of a biomarker for intestinal fibrosis,
especially in CD patients. Therefore, we wanted to investigate PRO-C16 as a marker of intestinal
fibrostenotic strictures in Crohn’s disease patients. “ These last sentences of the introduction are
not well written in my opinion.
-“Even though PRO-C16 did not reach statistical significance between the inactive vs. active
CD patients based on the CDAI score, we still observed numerically elevated PRO-C16 serum
levels in the active group. However, type XVI collagen has been shown to increase the
expression and activation of MMP-9 locally in tissue at the site of insult by immune cells,
e.g., macrophages and neutrophils[31]”. This could explain the elevated levels of PRO-C16
observed in Crohn’s disease patients with active disease, as MMP-9 tissue expression leads
to chronic intestinal mucosal damage[14–20, 32, 33]. This process is thought to be facilitated
by type XVI collagen’s ability to maintain adhesion of intestinal subepithelial myofibroblasts,
thus increasing the pathological development of intestinal fibrostenotic strictures[5]. “These
sentences are highly speculative and not very comprehensible. The link between MMP9 and
PRO-C16 is not explained. I suggest removing this part.
assistant