Title: Extracellular matrix remodeling proteins as biomarkers for clinical assessment and
treatment outcomes in eosinophilic esophagitis
Version: 1 Date: 24 Jan 2023
Reviewer's report:
Comments:
In this paper, the authors aim to identify serological biomarkers in a clinically well-characterized
group of adult EoE patients. Identification of reliable non-invasive markers for diagnosis of
EoE including endotypes and monitoring the success of various treatment interventions is a
major challenge in the field. This paper tries to address this question by analyzing a set of
markers related to tissue remodeling (extracellular matrix turnover (collagens)) and neutrophil
and macrophage activity. The difference observed while significant is very modest.  Also, the
relevance of these biomarkers to EoE as opposed to atopy is unclear and data presentation needs
more clarity.
Major points:
1. Nearly all EoE patients have other allergic disorders such as atopic dermatitis and asthma (see
details of the clinical trial published in DOI: 10.1111/nmo.14291). It is unclear if the biomarkers
assessed in the paper are specific to EoE or reflect the atopic status of the patients. What was
the rationale for choosing these biomarkers specifically for EoE?
2. This whole study represents a “discovery” cohort, but no validation cohort is reported. What
is the value of these biomarkers either alone or in combinations as related to the diagnosis and
treatment of EoE? While this point is discussed in the paper, it signifies the major limitation
and raises the question of whether these findings are related at all to EoE as it is presented in
the manuscript.
3. It would be beneficial to have the methodology explained in much more detail rather than
referring to previous publications. Please provide details on the ELISA kits used, such as the
manufacturer and the catalog number, units of measurement, and detection limits.
Minor points
1. Table 1 is confusing. What does Figure 1-5 in the first column mean? Does it have to include
the statistics? Is there a better way to present these sub-classifications? Maybe using a chart?
2. Related to it, do patients with more severe endotypes had a higher co-occurrence of other
atopies which may explain differences seen for example in Figure 2?
3. Table 4 is highly confusing. To what group comparison does the P-value refer? What are
the units for the expression of each marker? Please present as bar graphs (or similar) for the
individual biomarkers with individual values for each patient (to assess the distribution) and the
accompanied statistics.
4. What does Ratio (Y-axis in Figure 1E and 3D) represent?
5. Spelling errors in the text, please run the spelling check.
6. Some figures have Y-axis not starting from 0 which gives a visual impression of a stronger
effect (Ex. Fig 1 B, C, E)
7. I don’t understand Figure 4.
Title: Extracellular matrix remodeling proteins as biomarkers for clinical assessment and
treatment outcomes in eosinophilic esophagitis
Version: 1 Date: 24 Jan 2023
Reviewer's report:
Comments:
In this paper, the authors aim to identify serological biomarkers in a clinically well-characterized
group of adult EoE patients. Identification of reliable non-invasive markers for diagnosis of
EoE including endotypes and monitoring the success of various treatment interventions is a
major challenge in the field. This paper tries to address this question by analyzing a set of
markers related to tissue remodeling (extracellular matrix turnover (collagens)) and neutrophil
and macrophage activity. The difference observed while significant is very modest.  Also, the
relevance of these biomarkers to EoE as opposed to atopy is unclear and data presentation needs
more clarity.
Major points:
1. Nearly all EoE patients have other allergic disorders such as atopic dermatitis and asthma (see
details of the clinical trial published in DOI: 10.1111/nmo.14291). It is unclear if the biomarkers
assessed in the paper are specific to EoE or reflect the atopic status of the patients. What was
the rationale for choosing these biomarkers specifically for EoE?
2. This whole study represents a “discovery” cohort, but no validation cohort is reported. What
is the value of these biomarkers either alone or in combinations as related to the diagnosis and
treatment of EoE? While this point is discussed in the paper, it signifies the major limitation
and raises the question of whether these findings are related at all to EoE as it is presented in
the manuscript.
3. It would be beneficial to have the methodology explained in much more detail rather than
referring to previous publications. Please provide details on the ELISA kits used, such as the
manufacturer and the catalog number, units of measurement, and detection limits.
Minor points
1. Table 1 is confusing. What does Figure 1-5 in the first column mean? Does it have to include
the statistics? Is there a better way to present these sub-classifications? Maybe using a chart?
2. Related to it, do patients with more severe endotypes had a higher co-occurrence of other
atopies which may explain differences seen for example in Figure 2?
3. Table 4 is highly confusing. To what group comparison does the P-value refer? What are
the units for the expression of each marker? Please present as bar graphs (or similar) for the
individual biomarkers with individual values for each patient (to assess the distribution) and the
accompanied statistics.
4. What does Ratio (Y-axis in Figure 1E and 3D) represent?
5. Spelling errors in the text, please run the spelling check.
6. Some figures have Y-axis not starting from 0 which gives a visual impression of a stronger
effect (Ex. Fig 1 B, C, E)
7. I don’t understand Figure 4.
Please review this paper.
user
Title: Extracellular matrix remodeling proteins as biomarkers for clinical assessment and
treatment outcomes in eosinophilic esophagitis
Version: 1 Date: 24 Jan 2023
Reviewer's report:
Comments:
In this paper, the authors aim to identify serological biomarkers in a clinically well-characterized
group of adult EoE patients. Identification of reliable non-invasive markers for diagnosis of
EoE including endotypes and monitoring the success of various treatment interventions is a
major challenge in the field. This paper tries to address this question by analyzing a set of
markers related to tissue remodeling (extracellular matrix turnover (collagens)) and neutrophil
and macrophage activity. The difference observed while significant is very modest.  Also, the
relevance of these biomarkers to EoE as opposed to atopy is unclear and data presentation needs
more clarity.
Major points:
1. Nearly all EoE patients have other allergic disorders such as atopic dermatitis and asthma (see
details of the clinical trial published in DOI: 10.1111/nmo.14291). It is unclear if the biomarkers
assessed in the paper are specific to EoE or reflect the atopic status of the patients. What was
the rationale for choosing these biomarkers specifically for EoE?
2. This whole study represents a “discovery” cohort, but no validation cohort is reported. What
is the value of these biomarkers either alone or in combinations as related to the diagnosis and
treatment of EoE? While this point is discussed in the paper, it signifies the major limitation
and raises the question of whether these findings are related at all to EoE as it is presented in
the manuscript.
3. It would be beneficial to have the methodology explained in much more detail rather than
referring to previous publications. Please provide details on the ELISA kits used, such as the
manufacturer and the catalog number, units of measurement, and detection limits.
Minor points
1. Table 1 is confusing. What does Figure 1-5 in the first column mean? Does it have to include
the statistics? Is there a better way to present these sub-classifications? Maybe using a chart?
2. Related to it, do patients with more severe endotypes had a higher co-occurrence of other
atopies which may explain differences seen for example in Figure 2?
3. Table 4 is highly confusing. To what group comparison does the P-value refer? What are
the units for the expression of each marker? Please present as bar graphs (or similar) for the
individual biomarkers with individual values for each patient (to assess the distribution) and the
accompanied statistics.
4. What does Ratio (Y-axis in Figure 1E and 3D) represent?
5. Spelling errors in the text, please run the spelling check.
6. Some figures have Y-axis not starting from 0 which gives a visual impression of a stronger
effect (Ex. Fig 1 B, C, E)
7. I don’t understand Figure 4.
assistant