Title: Immunological biomarkers at birth and later risk of celiac disease
Version: 1 Date: 22 Dec 2024
Reviewer's report:
Ulnes et al have tested some novel assays to measure immune subsets with a focus on total T
cells and Bcells from biobanked dried blood spots. They have access to a large historical biobank
and have information on infants that went on to develop CeD. They then determined there was
no correlation between the immune subsets and CeD vs controls. This has some novelty as such
assays have not been tested in CeD cohorts. The ability to test for disease risk on dried blood
spots at birth is also of interest. Some weaknesses in that the control cohorts are less characterized
than the CeD cohort. I suggest some amendments to the article.
1) I felt that for an article submitted to a Gastroenterology journal there may be a need for
additional background on the methods used. Perhaps additional description around the literature
where the methods have been compared to other more standard methods such as flow cytometry?
For example have approximate frequencies measured in these assays been compared to a
TruCOUNT like method? Such methods only require 50uL whole blood. Is there any literature
surrounding the robustness of the assay perhaps using older individuals that allow more sampling
to occur? E.g intra-assay variation, inter-assay variation? Background section would benefit
from a little extra background on the actual differences observed in other disease settings and
whether these TRECs and KRECs, epigenetic estimates were compared to other assays within
these other studies. Prefer some of this detail to be in the main text rather than the supplementary
2) The authors mention the limitation of not having data on the controls but there is no
explanation why no questionnaire data was available for this group. It would be useful for this
to be explained.
3) Were there any correlations between a “higher” or “lower” count in the TREC and T cells
within the epigenetic counts? Or KREC and B cells within the same individuals?
4) Some of the literature in the discussion needs to be more explicit whether this refers to CeD
or other cohorts.
5) Expansion of the detail in the figure legend for figure S2 would be beneficial.
Title: Immunological biomarkers at birth and later risk of celiac disease
Version: 1 Date: 22 Dec 2024
Reviewer's report:
Ulnes et al have tested some novel assays to measure immune subsets with a focus on total T
cells and Bcells from biobanked dried blood spots. They have access to a large historical biobank
and have information on infants that went on to develop CeD. They then determined there was
no correlation between the immune subsets and CeD vs controls. This has some novelty as such
assays have not been tested in CeD cohorts. The ability to test for disease risk on dried blood
spots at birth is also of interest. Some weaknesses in that the control cohorts are less characterized
than the CeD cohort. I suggest some amendments to the article.
1) I felt that for an article submitted to a Gastroenterology journal there may be a need for
additional background on the methods used. Perhaps additional description around the literature
where the methods have been compared to other more standard methods such as flow cytometry?
For example have approximate frequencies measured in these assays been compared to a
TruCOUNT like method? Such methods only require 50uL whole blood. Is there any literature
surrounding the robustness of the assay perhaps using older individuals that allow more sampling
to occur? E.g intra-assay variation, inter-assay variation? Background section would benefit
from a little extra background on the actual differences observed in other disease settings and
whether these TRECs and KRECs, epigenetic estimates were compared to other assays within
these other studies. Prefer some of this detail to be in the main text rather than the supplementary
2) The authors mention the limitation of not having data on the controls but there is no
explanation why no questionnaire data was available for this group. It would be useful for this
to be explained.
3) Were there any correlations between a “higher” or “lower” count in the TREC and T cells
within the epigenetic counts? Or KREC and B cells within the same individuals?
4) Some of the literature in the discussion needs to be more explicit whether this refers to CeD
or other cohorts.
5) Expansion of the detail in the figure legend for figure S2 would be beneficial.
Please review this paper.
user
Title: Immunological biomarkers at birth and later risk of celiac disease
Version: 1 Date: 22 Dec 2024
Reviewer's report:
Ulnes et al have tested some novel assays to measure immune subsets with a focus on total T
cells and Bcells from biobanked dried blood spots. They have access to a large historical biobank
and have information on infants that went on to develop CeD. They then determined there was
no correlation between the immune subsets and CeD vs controls. This has some novelty as such
assays have not been tested in CeD cohorts. The ability to test for disease risk on dried blood
spots at birth is also of interest. Some weaknesses in that the control cohorts are less characterized
than the CeD cohort. I suggest some amendments to the article.
1) I felt that for an article submitted to a Gastroenterology journal there may be a need for
additional background on the methods used. Perhaps additional description around the literature
where the methods have been compared to other more standard methods such as flow cytometry?
For example have approximate frequencies measured in these assays been compared to a
TruCOUNT like method? Such methods only require 50uL whole blood. Is there any literature
surrounding the robustness of the assay perhaps using older individuals that allow more sampling
to occur? E.g intra-assay variation, inter-assay variation? Background section would benefit
from a little extra background on the actual differences observed in other disease settings and
whether these TRECs and KRECs, epigenetic estimates were compared to other assays within
these other studies. Prefer some of this detail to be in the main text rather than the supplementary
2) The authors mention the limitation of not having data on the controls but there is no
explanation why no questionnaire data was available for this group. It would be useful for this
to be explained.
3) Were there any correlations between a “higher” or “lower” count in the TREC and T cells
within the epigenetic counts? Or KREC and B cells within the same individuals?
4) Some of the literature in the discussion needs to be more explicit whether this refers to CeD
or other cohorts.
5) Expansion of the detail in the figure legend for figure S2 would be beneficial.
assistant