Reviewer's report 
 Rhinosinusitis derived Staphylococcal enterotoxin B acts as a Trojan horse in the Title: 
pathogenesis of ulcerative colitis 
 1  16 May 2005 Version: Date: 
 elizabeth furrie Reviewer: 
Reviewer's report: 
General 
The authors describe an interesting study where they have selected a group of patients with UC and chronic rhinosinusitis (CRS). They have shown that surgical treatment of the CRS has a dramatic effect on the disease state of the patients UC. This is an interesting observation where as the 
patients CRS is resolved so is their UC. However there are some major points which require 
clarification. 
------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can be reached) 
1. Having read the paper I cannot see that it adheres to the title. The authors need to explain in what 
way SEB is a Trojan horse for UC. 
2. Paragraph 2 in the introduction. The authors start to explain the role of the toxins produced by S. 
aureus and then seem to run out of steam with the throw awat comment and so on!!!!! It is 
imperative that they adequately describe the function of SEB, at least in the context of the mucosal 
immune response and antigen presentation, for an the reader to fully understand the reason why 
these researchers are interested in SEB superantigen. What they have written is in no way 
acceptable. 3. Page 6, line 3. Could the authors please explain properly the potental role of SEB in barrier 
dysfunction and why this would be important in UC pathogenesis (cf other noxious substances). 
4. Page 6 line 13. Why do the authors suddenly mention LPS (a product of Gram negative bacteria) 
in isolation without any explanation, surely they are not equating it with SEB? 5. The authors must provide a more complete explanation of the surgery procedure and all 
medication before and after the surgical procedure. This is essential since the UC control has no 
surgical intervention. This is particularly crucial if the surgery patients are given antibiotics pre or post surgery since this could dramatically influence UC disease state. 6. Reference 32 refers to only the CRP measurements and not the SEB specific IgE measurements, 
please include additional reference. 
7. It is highly debatable whether the comparison of a swab control with whole tissue as the test population is acceptable. Can the authors make some estimation of surface area covered by the two techniques. Also are there areas that are inaccessible to the swab which would be accessible in the 
tissue resection? 
8. Why were two pieces taken at the edge of ulcers in the UC patients. Would it not have been better 
to take biopsies from areas of inflammation and areas of normality in the moderate UC you are 
studying. How do you define moderate- is it on clinical score? 
9. Page 12 line 13-14 starting CO2 something has happened to your sentence and it is totally 
incomprehensible- please rewrite, line 19 centrifuge speed should be quoted in g not rpm. 10. The UC patients reduce prednisolone levels, levels of CRP and also their colitis score is dramatically reduced. This is shown convincingly in figures 1-3. However statistical analyses for 
reductions should be carried out to show significance. The use of the phrase significant difference 
absolutely requires a statistical measurement. 
11. Please give numbers for patients with S,aureus growth. The stement from most patients is not 
scientific. 
12. Figure 5. There is no such word as correlationship- furthermore the Figure as it stands shows neither a relationship nor a correlation. This figure must be redrawn with some though as to what exactly the authors are trying to demonstrate. 
13. Figure 6- the bands on the agarose gel appear to be of different sizes- This raises the question 
of whether these really are S. aureus The authors should sequence the PCR products and absolutely identify them as S. aureus. 14. Figure 7. This shows a significant decrease in Total IgE in the treatment group over control. 
Therefore the reduction seen in the anti-SEB may just be due to the decrease in total IgE. The 
authors need to present the anti-SEB results as a ratio of Total IgE. 
15. Figure 8- All the controls are missing from this figure so it is impossible to say anything about it. 
16. Figure 9-A CRS alone after treatment would have added to this figure. 
17. Figure 10 shows nothing new and in its present state should be omitted 
18. Figure 11- Could the authors please explain why the UC/ CRS (B) and the UC/CRS+SEB (D) look identical. This would appear to imply that there are some inconsistencies in the mast cell appearances. 
19. Figure 12- This figure shows some interesting data which is completely negated by the statistical
analyses which render in incomprehensible. Please redo. 20. Discussion- got significantly improvement This makes no grammatical sense and also since statistics were not performed on that data you cannot say anything is significant. 
21. Book et al states that CRS is a particular problem in CD patients not UC- would the authors 
please comment. 
22. All the evidence the authors have provided for SEB playing a role in UC pathogenesis has been 
highly circumstantial. You have presented no evidence that absolutely tries SEB with UC 
pathogenesis. 
23. The authors need to duscuss their results in more depth. What is the role of antigen sampling by 
Peyers patches ? Which cells are SEB positive in the Lamina propria why have they not been identified. Are the greatly increased numbers of cells seen in UC mucosa confounding the results? 
The reduction of CRP could be due to the reduction in UC. I fail to understand how this is 
synergistic, it is mearly additive- when you reduce inflammation in the body CRP also decreases. 
24. Finally it is absolutely imperative that the authors seek help in the writing of this paper from someone who has English as a first language and preferably scientific English. The language 
requires serious editorial help. 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the 
author can be trusted to correct) 
------------------------------------------------------------------------------- 
Discretionary Revisions (which the author can choose to ignore) 
 Unable to decide on acceptance or rejection until the authors have responded to the What next?: 
major compulsory revisions 
 An article whose findings are important to those with closely related research Level of interest: 
interests 
 Not suitable for publication unless extensively edited Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests 
Reviewer's report 
 Rhinosinusitis derived Staphylococcal enterotoxin B acts as a Trojan horse in the Title: 
pathogenesis of ulcerative colitis 
 1  16 May 2005 Version: Date: 
 elizabeth furrie Reviewer: 
Reviewer's report: 
General 
The authors describe an interesting study where they have selected a group of patients with UC and chronic rhinosinusitis (CRS). They have shown that surgical treatment of the CRS has a dramatic effect on the disease state of the patients UC. This is an interesting observation where as the 
patients CRS is resolved so is their UC. However there are some major points which require 
clarification. 
------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can be reached) 
1. Having read the paper I cannot see that it adheres to the title. The authors need to explain in what 
way SEB is a Trojan horse for UC. 
2. Paragraph 2 in the introduction. The authors start to explain the role of the toxins produced by S. 
aureus and then seem to run out of steam with the throw awat comment and so on!!!!! It is 
imperative that they adequately describe the function of SEB, at least in the context of the mucosal 
immune response and antigen presentation, for an the reader to fully understand the reason why 
these researchers are interested in SEB superantigen. What they have written is in no way 
acceptable. 3. Page 6, line 3. Could the authors please explain properly the potental role of SEB in barrier 
dysfunction and why this would be important in UC pathogenesis (cf other noxious substances). 
4. Page 6 line 13. Why do the authors suddenly mention LPS (a product of Gram negative bacteria) 
in isolation without any explanation, surely they are not equating it with SEB? 5. The authors must provide a more complete explanation of the surgery procedure and all 
medication before and after the surgical procedure. This is essential since the UC control has no 
surgical intervention. This is particularly crucial if the surgery patients are given antibiotics pre or post surgery since this could dramatically influence UC disease state. 6. Reference 32 refers to only the CRP measurements and not the SEB specific IgE measurements, 
please include additional reference. 
7. It is highly debatable whether the comparison of a swab control with whole tissue as the test population is acceptable. Can the authors make some estimation of surface area covered by the two techniques. Also are there areas that are inaccessible to the swab which would be accessible in the 
tissue resection? 
8. Why were two pieces taken at the edge of ulcers in the UC patients. Would it not have been better 
to take biopsies from areas of inflammation and areas of normality in the moderate UC you are 
studying. How do you define moderate- is it on clinical score? 
9. Page 12 line 13-14 starting CO2 something has happened to your sentence and it is totally 
incomprehensible- please rewrite, line 19 centrifuge speed should be quoted in g not rpm. 10. The UC patients reduce prednisolone levels, levels of CRP and also their colitis score is dramatically reduced. This is shown convincingly in figures 1-3. However statistical analyses for 
reductions should be carried out to show significance. The use of the phrase significant difference 
absolutely requires a statistical measurement. 
11. Please give numbers for patients with S,aureus growth. The stement from most patients is not 
scientific. 
12. Figure 5. There is no such word as correlationship- furthermore the Figure as it stands shows neither a relationship nor a correlation. This figure must be redrawn with some though as to what exactly the authors are trying to demonstrate. 
13. Figure 6- the bands on the agarose gel appear to be of different sizes- This raises the question 
of whether these really are S. aureus The authors should sequence the PCR products and absolutely identify them as S. aureus. 14. Figure 7. This shows a significant decrease in Total IgE in the treatment group over control. 
Therefore the reduction seen in the anti-SEB may just be due to the decrease in total IgE. The 
authors need to present the anti-SEB results as a ratio of Total IgE. 
15. Figure 8- All the controls are missing from this figure so it is impossible to say anything about it. 
16. Figure 9-A CRS alone after treatment would have added to this figure. 
17. Figure 10 shows nothing new and in its present state should be omitted 
18. Figure 11- Could the authors please explain why the UC/ CRS (B) and the UC/CRS+SEB (D) look identical. This would appear to imply that there are some inconsistencies in the mast cell appearances. 
19. Figure 12- This figure shows some interesting data which is completely negated by the statistical
analyses which render in incomprehensible. Please redo. 20. Discussion- got significantly improvement This makes no grammatical sense and also since statistics were not performed on that data you cannot say anything is significant. 
21. Book et al states that CRS is a particular problem in CD patients not UC- would the authors 
please comment. 
22. All the evidence the authors have provided for SEB playing a role in UC pathogenesis has been 
highly circumstantial. You have presented no evidence that absolutely tries SEB with UC 
pathogenesis. 
23. The authors need to duscuss their results in more depth. What is the role of antigen sampling by 
Peyers patches ? Which cells are SEB positive in the Lamina propria why have they not been identified. Are the greatly increased numbers of cells seen in UC mucosa confounding the results? 
The reduction of CRP could be due to the reduction in UC. I fail to understand how this is 
synergistic, it is mearly additive- when you reduce inflammation in the body CRP also decreases. 
24. Finally it is absolutely imperative that the authors seek help in the writing of this paper from someone who has English as a first language and preferably scientific English. The language 
requires serious editorial help. 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the 
author can be trusted to correct) 
------------------------------------------------------------------------------- 
Discretionary Revisions (which the author can choose to ignore) 
 Unable to decide on acceptance or rejection until the authors have responded to the What next?: 
major compulsory revisions 
 An article whose findings are important to those with closely related research Level of interest: 
interests 
 Not suitable for publication unless extensively edited Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests 
Please review this paper.
user
Reviewer's report 
 Rhinosinusitis derived Staphylococcal enterotoxin B acts as a Trojan horse in the Title: 
pathogenesis of ulcerative colitis 
 1  16 May 2005 Version: Date: 
 elizabeth furrie Reviewer: 
Reviewer's report: 
General 
The authors describe an interesting study where they have selected a group of patients with UC and chronic rhinosinusitis (CRS). They have shown that surgical treatment of the CRS has a dramatic effect on the disease state of the patients UC. This is an interesting observation where as the 
patients CRS is resolved so is their UC. However there are some major points which require 
clarification. 
------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can be reached) 
1. Having read the paper I cannot see that it adheres to the title. The authors need to explain in what 
way SEB is a Trojan horse for UC. 
2. Paragraph 2 in the introduction. The authors start to explain the role of the toxins produced by S. 
aureus and then seem to run out of steam with the throw awat comment and so on!!!!! It is 
imperative that they adequately describe the function of SEB, at least in the context of the mucosal 
immune response and antigen presentation, for an the reader to fully understand the reason why 
these researchers are interested in SEB superantigen. What they have written is in no way 
acceptable. 3. Page 6, line 3. Could the authors please explain properly the potental role of SEB in barrier 
dysfunction and why this would be important in UC pathogenesis (cf other noxious substances). 
4. Page 6 line 13. Why do the authors suddenly mention LPS (a product of Gram negative bacteria) 
in isolation without any explanation, surely they are not equating it with SEB? 5. The authors must provide a more complete explanation of the surgery procedure and all 
medication before and after the surgical procedure. This is essential since the UC control has no 
surgical intervention. This is particularly crucial if the surgery patients are given antibiotics pre or post surgery since this could dramatically influence UC disease state. 6. Reference 32 refers to only the CRP measurements and not the SEB specific IgE measurements, 
please include additional reference. 
7. It is highly debatable whether the comparison of a swab control with whole tissue as the test population is acceptable. Can the authors make some estimation of surface area covered by the two techniques. Also are there areas that are inaccessible to the swab which would be accessible in the 
tissue resection? 
8. Why were two pieces taken at the edge of ulcers in the UC patients. Would it not have been better 
to take biopsies from areas of inflammation and areas of normality in the moderate UC you are 
studying. How do you define moderate- is it on clinical score? 
9. Page 12 line 13-14 starting CO2 something has happened to your sentence and it is totally 
incomprehensible- please rewrite, line 19 centrifuge speed should be quoted in g not rpm. 10. The UC patients reduce prednisolone levels, levels of CRP and also their colitis score is dramatically reduced. This is shown convincingly in figures 1-3. However statistical analyses for 
reductions should be carried out to show significance. The use of the phrase significant difference 
absolutely requires a statistical measurement. 
11. Please give numbers for patients with S,aureus growth. The stement from most patients is not 
scientific. 
12. Figure 5. There is no such word as correlationship- furthermore the Figure as it stands shows neither a relationship nor a correlation. This figure must be redrawn with some though as to what exactly the authors are trying to demonstrate. 
13. Figure 6- the bands on the agarose gel appear to be of different sizes- This raises the question 
of whether these really are S. aureus The authors should sequence the PCR products and absolutely identify them as S. aureus. 14. Figure 7. This shows a significant decrease in Total IgE in the treatment group over control. 
Therefore the reduction seen in the anti-SEB may just be due to the decrease in total IgE. The 
authors need to present the anti-SEB results as a ratio of Total IgE. 
15. Figure 8- All the controls are missing from this figure so it is impossible to say anything about it. 
16. Figure 9-A CRS alone after treatment would have added to this figure. 
17. Figure 10 shows nothing new and in its present state should be omitted 
18. Figure 11- Could the authors please explain why the UC/ CRS (B) and the UC/CRS+SEB (D) look identical. This would appear to imply that there are some inconsistencies in the mast cell appearances. 
19. Figure 12- This figure shows some interesting data which is completely negated by the statistical
analyses which render in incomprehensible. Please redo. 20. Discussion- got significantly improvement This makes no grammatical sense and also since statistics were not performed on that data you cannot say anything is significant. 
21. Book et al states that CRS is a particular problem in CD patients not UC- would the authors 
please comment. 
22. All the evidence the authors have provided for SEB playing a role in UC pathogenesis has been 
highly circumstantial. You have presented no evidence that absolutely tries SEB with UC 
pathogenesis. 
23. The authors need to duscuss their results in more depth. What is the role of antigen sampling by 
Peyers patches ? Which cells are SEB positive in the Lamina propria why have they not been identified. Are the greatly increased numbers of cells seen in UC mucosa confounding the results? 
The reduction of CRP could be due to the reduction in UC. I fail to understand how this is 
synergistic, it is mearly additive- when you reduce inflammation in the body CRP also decreases. 
24. Finally it is absolutely imperative that the authors seek help in the writing of this paper from someone who has English as a first language and preferably scientific English. The language 
requires serious editorial help. 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the 
author can be trusted to correct) 
------------------------------------------------------------------------------- 
Discretionary Revisions (which the author can choose to ignore) 
 Unable to decide on acceptance or rejection until the authors have responded to the What next?: 
major compulsory revisions 
 An article whose findings are important to those with closely related research Level of interest: 
interests 
 Not suitable for publication unless extensively edited Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests 
assistant