Reviewer's report
Title:Screening for celiac disease in 1st degree relatives: a 10-year follow-up
study
Version: 4Date:25 September 2013
Reviewer: C M Frank Kneepkens
Reviewer's report:
The authors have done a great job in improving the manuscript. I will confine my
comments essentially to the points I raised earlier.
Major compulsory revisions
1. Results, page 6: The authors have not reacted to my first point of criticism:
“As, however, 2 of these five had Marsh 1 mucosa and are therefore not biopsy
proven, the real harvest might be considered lower.” According to present
standards, pediatric patients with TG2A < 10x ULN (~100) need a biopsy to
confirm CD, while patients (adult and pediatric) with Marsh 1 (no villous atrophy,
even no crypt hyperplasia) are not considered as having CD (compare ref 23).
They may become CD patients, but serology and histology also may return to
normal. Therefore, I strongly advice to confine the ‘yield’ of CD-proven cases in
the second round to 3. So, in the second paragraph, change the text into “Five of
these newly seroconverted subjects underwent a duodenal biopsy that showed
mucosal abnormalities confirming their diagnosis of celiac disease in three of
them.”, and above Table 1, “CD was confirmed in three…”. Same for figure 1. Of
course this has impact on the related calculations as well.
2. Discussion, bottom of page 7 and first lines of page 8: these 3 patients,
despite having positive TG2A, are negative for EmA and therefore are unlikely to
have CD at this point. This should be stressed while discussing these data.
Minor essential revisions
3. In the Introduction, page 2, line 4: ‘that may result’ should be changed into
‘resulting’. There should be a minimum of histologic damage (at least Marsh 2)
before CD can be diagnosed. This remains a weak point in this study. See below.
4. Page 5, under ‘HLA typing’: “To further confirm the diagnosis of CD…” Please
change ‘confirm’ into ‘support’. The authors rightly refer to ref 27, underscoring
that HLA typing cannot be used to confirm CD, only to reject the diagnosis.
Discretionary revisions
5. Language and style are considerably improved. There are some words left that
the authors might want to change for better understanding: page 2, line 5 of the
second paragraph: ‘presumably’ should read ‘presumed’; page 7, third
paragraph, line 5: change ‘dynamics’ into ‘dynamic’; page 7, line 5 from below:
‘retrieved’ probably is better changed into ‘retested’; page 8, conclusion, line 1:
‘coincident’: better would be e.g. ‘in line’.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
Reviewer's report
Title:Screening for celiac disease in 1st degree relatives: a 10-year follow-up
study
Version: 4Date:25 September 2013
Reviewer: C M Frank Kneepkens
Reviewer's report:
The authors have done a great job in improving the manuscript. I will confine my
comments essentially to the points I raised earlier.
Major compulsory revisions
1. Results, page 6: The authors have not reacted to my first point of criticism:
“As, however, 2 of these five had Marsh 1 mucosa and are therefore not biopsy
proven, the real harvest might be considered lower.” According to present
standards, pediatric patients with TG2A < 10x ULN (~100) need a biopsy to
confirm CD, while patients (adult and pediatric) with Marsh 1 (no villous atrophy,
even no crypt hyperplasia) are not considered as having CD (compare ref 23).
They may become CD patients, but serology and histology also may return to
normal. Therefore, I strongly advice to confine the ‘yield’ of CD-proven cases in
the second round to 3. So, in the second paragraph, change the text into “Five of
these newly seroconverted subjects underwent a duodenal biopsy that showed
mucosal abnormalities confirming their diagnosis of celiac disease in three of
them.”, and above Table 1, “CD was confirmed in three…”. Same for figure 1. Of
course this has impact on the related calculations as well.
2. Discussion, bottom of page 7 and first lines of page 8: these 3 patients,
despite having positive TG2A, are negative for EmA and therefore are unlikely to
have CD at this point. This should be stressed while discussing these data.
Minor essential revisions
3. In the Introduction, page 2, line 4: ‘that may result’ should be changed into
‘resulting’. There should be a minimum of histologic damage (at least Marsh 2)
before CD can be diagnosed. This remains a weak point in this study. See below.
4. Page 5, under ‘HLA typing’: “To further confirm the diagnosis of CD…” Please
change ‘confirm’ into ‘support’. The authors rightly refer to ref 27, underscoring
that HLA typing cannot be used to confirm CD, only to reject the diagnosis.
Discretionary revisions
5. Language and style are considerably improved. There are some words left that
the authors might want to change for better understanding: page 2, line 5 of the
second paragraph: ‘presumably’ should read ‘presumed’; page 7, third
paragraph, line 5: change ‘dynamics’ into ‘dynamic’; page 7, line 5 from below:
‘retrieved’ probably is better changed into ‘retested’; page 8, conclusion, line 1:
‘coincident’: better would be e.g. ‘in line’.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
Please review this paper.
user
Reviewer's report
Title:Screening for celiac disease in 1st degree relatives: a 10-year follow-up
study
Version: 4Date:25 September 2013
Reviewer: C M Frank Kneepkens
Reviewer's report:
The authors have done a great job in improving the manuscript. I will confine my
comments essentially to the points I raised earlier.
Major compulsory revisions
1. Results, page 6: The authors have not reacted to my first point of criticism:
“As, however, 2 of these five had Marsh 1 mucosa and are therefore not biopsy
proven, the real harvest might be considered lower.” According to present
standards, pediatric patients with TG2A < 10x ULN (~100) need a biopsy to
confirm CD, while patients (adult and pediatric) with Marsh 1 (no villous atrophy,
even no crypt hyperplasia) are not considered as having CD (compare ref 23).
They may become CD patients, but serology and histology also may return to
normal. Therefore, I strongly advice to confine the ‘yield’ of CD-proven cases in
the second round to 3. So, in the second paragraph, change the text into “Five of
these newly seroconverted subjects underwent a duodenal biopsy that showed
mucosal abnormalities confirming their diagnosis of celiac disease in three of
them.”, and above Table 1, “CD was confirmed in three…”. Same for figure 1. Of
course this has impact on the related calculations as well.
2. Discussion, bottom of page 7 and first lines of page 8: these 3 patients,
despite having positive TG2A, are negative for EmA and therefore are unlikely to
have CD at this point. This should be stressed while discussing these data.
Minor essential revisions
3. In the Introduction, page 2, line 4: ‘that may result’ should be changed into
‘resulting’. There should be a minimum of histologic damage (at least Marsh 2)
before CD can be diagnosed. This remains a weak point in this study. See below.
4. Page 5, under ‘HLA typing’: “To further confirm the diagnosis of CD…” Please
change ‘confirm’ into ‘support’. The authors rightly refer to ref 27, underscoring
that HLA typing cannot be used to confirm CD, only to reject the diagnosis.
Discretionary revisions
5. Language and style are considerably improved. There are some words left that
the authors might want to change for better understanding: page 2, line 5 of the
second paragraph: ‘presumably’ should read ‘presumed’; page 7, third
paragraph, line 5: change ‘dynamics’ into ‘dynamic’; page 7, line 5 from below:
‘retrieved’ probably is better changed into ‘retested’; page 8, conclusion, line 1:
‘coincident’: better would be e.g. ‘in line’.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
assistant