Reviewer's report 
 Complement activation capacity in plasma before and during high-dose prednisolone Title: 
treatment and tapering in exacerbations of Crohn's disease and ulcerative colitis. 
 4  22 July 2005 Version: Date: 
 Fruhling V Rijsdijk Reviewer: 
Reviewer's report: 
General 
------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can 
be reached) 
Terminology: 
The authors refer to Mann Whitney test but it’s probably better to call it Mann Whitney U test. The 
authors refer to Wilcoxon signed rank sum test. This is confusing since there are two similarly 
named tests: (i) Wilcoxon signed-rank test (non-parametric alternative to paired Student’s t-test); (ii) Rank Sum test (invented by Wilcoxon, to test 2 independent samples). Presumably, they mean the 
first. 
Abstract 
I question whether it’s necessary to sum all types of statistical test used in the abstract, but if it is, 
the authors omit to mention Spearman’s rank correlation coefficient (later referred to in the Statistics 
section). 
Statistics section of Methods 
My main criticism of the Statistics section in Methods is that the authors did not mention the order in 
which the tests were used. Order of tests used is important, for instance it’s possible to find pairwise 
significance in a treatment effect anova, even when the anova shows non-significance in differences 
in means by treatment effect. The answer to this paradox is that the anova is correct; the other is a 
false positive. The correct procedure is to do the anova first. Only if the anova indicates there are sig 
differences in group means should you then go on to investigate (using pair-wise tests) which of 
those group means differ significantly, and correction for multiple testing would be in order. The authors do mention to have followed this procedure (in their reply to the report of reviewer 1), but they should actually describe this in the paper itself. 
Results 
Page 10 : The significance test to show elevation of both C pathways in CD patients as compared to healthy controls and UC patients should have been conducted with the Mann-Whitney test, not the 
Wilcoxon test. I assume it’s just a typo? The same is true for the CRP and orosmucoid tests (Page 
10-11) if the test was meant to be between CD and UC patients? 
Discussion 
Page 11, first paragraph and Page 12 second paragraph: decreases in CRP, orosomucoid and 
leucocyte count are discussed as additional support for a general down-regulation in immune activation. However, these decreases were not reported to be significant in the Results section. If these are merely trends, they should be stated as such. 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the 
author can be trusted to correct) 
(1) In the abstract ‘complement activation’ is abbreviated as C activation, and later in the paper 
(Page 7) and tables as AC. Why not simply CA? 
(2) Page 1: results, line 8, use ‘persisted’ instead of ‘sustained’. (3) Page 4: What is the putative auto-antigen called? 
(4) Page 4: ‘The effects of glucocorticoids….. Split up sentence in two: ‘The effects of 
glucocorticoids on C activation have been reported inconsistently. This is partly explained by the ………………’. Also, last sentence: ‘…, and inhibiting …’ (5) Page 5: I don’t think it’s appropriate to end an introduction with a summary of the results. 
(6) Page 6: ‘The patients still treated….’ 
(7) Page 9: Results. With ‘all C data’ do the authors mean the MBL measures as well? (8) Page 12: line 4: may exceed the wall of … , please check English. 
Typo’s: 
Page 1: adres > address Page 11 valuesobtained > values obtained 
------------------------------------------------------------------------------- 
Discretionary Revisions (which the author can choose to ignore) 
none 
 Accept after minor essential revisions What next?: 
 An article whose findings are important to those with closely related research Level of interest: 
interests 
 Acceptable Quality of written English: 
 Yes Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests 
Reviewer's report 
 Complement activation capacity in plasma before and during high-dose prednisolone Title: 
treatment and tapering in exacerbations of Crohn's disease and ulcerative colitis. 
 4  22 July 2005 Version: Date: 
 Fruhling V Rijsdijk Reviewer: 
Reviewer's report: 
General 
------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can 
be reached) 
Terminology: 
The authors refer to Mann Whitney test but it’s probably better to call it Mann Whitney U test. The 
authors refer to Wilcoxon signed rank sum test. This is confusing since there are two similarly 
named tests: (i) Wilcoxon signed-rank test (non-parametric alternative to paired Student’s t-test); (ii) Rank Sum test (invented by Wilcoxon, to test 2 independent samples). Presumably, they mean the 
first. 
Abstract 
I question whether it’s necessary to sum all types of statistical test used in the abstract, but if it is, 
the authors omit to mention Spearman’s rank correlation coefficient (later referred to in the Statistics 
section). 
Statistics section of Methods 
My main criticism of the Statistics section in Methods is that the authors did not mention the order in 
which the tests were used. Order of tests used is important, for instance it’s possible to find pairwise 
significance in a treatment effect anova, even when the anova shows non-significance in differences 
in means by treatment effect. The answer to this paradox is that the anova is correct; the other is a 
false positive. The correct procedure is to do the anova first. Only if the anova indicates there are sig 
differences in group means should you then go on to investigate (using pair-wise tests) which of 
those group means differ significantly, and correction for multiple testing would be in order. The authors do mention to have followed this procedure (in their reply to the report of reviewer 1), but they should actually describe this in the paper itself. 
Results 
Page 10 : The significance test to show elevation of both C pathways in CD patients as compared to healthy controls and UC patients should have been conducted with the Mann-Whitney test, not the 
Wilcoxon test. I assume it’s just a typo? The same is true for the CRP and orosmucoid tests (Page 
10-11) if the test was meant to be between CD and UC patients? 
Discussion 
Page 11, first paragraph and Page 12 second paragraph: decreases in CRP, orosomucoid and 
leucocyte count are discussed as additional support for a general down-regulation in immune activation. However, these decreases were not reported to be significant in the Results section. If these are merely trends, they should be stated as such. 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the 
author can be trusted to correct) 
(1) In the abstract ‘complement activation’ is abbreviated as C activation, and later in the paper 
(Page 7) and tables as AC. Why not simply CA? 
(2) Page 1: results, line 8, use ‘persisted’ instead of ‘sustained’. (3) Page 4: What is the putative auto-antigen called? 
(4) Page 4: ‘The effects of glucocorticoids….. Split up sentence in two: ‘The effects of 
glucocorticoids on C activation have been reported inconsistently. This is partly explained by the ………………’. Also, last sentence: ‘…, and inhibiting …’ (5) Page 5: I don’t think it’s appropriate to end an introduction with a summary of the results. 
(6) Page 6: ‘The patients still treated….’ 
(7) Page 9: Results. With ‘all C data’ do the authors mean the MBL measures as well? (8) Page 12: line 4: may exceed the wall of … , please check English. 
Typo’s: 
Page 1: adres > address Page 11 valuesobtained > values obtained 
------------------------------------------------------------------------------- 
Discretionary Revisions (which the author can choose to ignore) 
none 
 Accept after minor essential revisions What next?: 
 An article whose findings are important to those with closely related research Level of interest: 
interests 
 Acceptable Quality of written English: 
 Yes Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests 
Please review this paper.
user
Reviewer's report 
 Complement activation capacity in plasma before and during high-dose prednisolone Title: 
treatment and tapering in exacerbations of Crohn's disease and ulcerative colitis. 
 4  22 July 2005 Version: Date: 
 Fruhling V Rijsdijk Reviewer: 
Reviewer's report: 
General 
------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can 
be reached) 
Terminology: 
The authors refer to Mann Whitney test but it’s probably better to call it Mann Whitney U test. The 
authors refer to Wilcoxon signed rank sum test. This is confusing since there are two similarly 
named tests: (i) Wilcoxon signed-rank test (non-parametric alternative to paired Student’s t-test); (ii) Rank Sum test (invented by Wilcoxon, to test 2 independent samples). Presumably, they mean the 
first. 
Abstract 
I question whether it’s necessary to sum all types of statistical test used in the abstract, but if it is, 
the authors omit to mention Spearman’s rank correlation coefficient (later referred to in the Statistics 
section). 
Statistics section of Methods 
My main criticism of the Statistics section in Methods is that the authors did not mention the order in 
which the tests were used. Order of tests used is important, for instance it’s possible to find pairwise 
significance in a treatment effect anova, even when the anova shows non-significance in differences 
in means by treatment effect. The answer to this paradox is that the anova is correct; the other is a 
false positive. The correct procedure is to do the anova first. Only if the anova indicates there are sig 
differences in group means should you then go on to investigate (using pair-wise tests) which of 
those group means differ significantly, and correction for multiple testing would be in order. The authors do mention to have followed this procedure (in their reply to the report of reviewer 1), but they should actually describe this in the paper itself. 
Results 
Page 10 : The significance test to show elevation of both C pathways in CD patients as compared to healthy controls and UC patients should have been conducted with the Mann-Whitney test, not the 
Wilcoxon test. I assume it’s just a typo? The same is true for the CRP and orosmucoid tests (Page 
10-11) if the test was meant to be between CD and UC patients? 
Discussion 
Page 11, first paragraph and Page 12 second paragraph: decreases in CRP, orosomucoid and 
leucocyte count are discussed as additional support for a general down-regulation in immune activation. However, these decreases were not reported to be significant in the Results section. If these are merely trends, they should be stated as such. 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the 
author can be trusted to correct) 
(1) In the abstract ‘complement activation’ is abbreviated as C activation, and later in the paper 
(Page 7) and tables as AC. Why not simply CA? 
(2) Page 1: results, line 8, use ‘persisted’ instead of ‘sustained’. (3) Page 4: What is the putative auto-antigen called? 
(4) Page 4: ‘The effects of glucocorticoids….. Split up sentence in two: ‘The effects of 
glucocorticoids on C activation have been reported inconsistently. This is partly explained by the ………………’. Also, last sentence: ‘…, and inhibiting …’ (5) Page 5: I don’t think it’s appropriate to end an introduction with a summary of the results. 
(6) Page 6: ‘The patients still treated….’ 
(7) Page 9: Results. With ‘all C data’ do the authors mean the MBL measures as well? (8) Page 12: line 4: may exceed the wall of … , please check English. 
Typo’s: 
Page 1: adres > address Page 11 valuesobtained > values obtained 
------------------------------------------------------------------------------- 
Discretionary Revisions (which the author can choose to ignore) 
none 
 Accept after minor essential revisions What next?: 
 An article whose findings are important to those with closely related research Level of interest: 
interests 
 Acceptable Quality of written English: 
 Yes Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests 
assistant