Transition of Serum Cytokine Concentration in Rickettsia japonica Infection

Round 1

Reviewer 1 Report

The authors describe the immune response to Rickettsia japonica infection in seven patients. This manuscript is well written and clearly laid out with minor errors. There are a number of corrections that could be made along with clarification regarding some of the data and protocols.

Throughout the text there are a number of spaces missing between words and numbers (for example line 36 "... 4 females from70 to 87..." requires a space between 'from' and '70': "... 4 females from 70 to 87..."

Line 25: suggest change "...infection has been..." to "...infection was..."

Line 27: "...chilling..." correct to "...chills..."

Line 28: "...days following a tick bite."

Line 29: Need definition for "DIC"

Line 30: The sentence starting "Therefore, this worsening..." is not clear. Suggest an alternative sentence such as "Therefore, the deterioration of symptoms following a JSF infection needs to be understood." or similar.

Line 39: What PCR was used? please reference

Line 40: What ELISA/IFA assay was used? Please reference or explain

Line 42-43: Serum samples were also collected on days 3 and 7 for cases 1-3

Line 43: delete "the": "...-80C before use."

Line 44: I would recommend grouping the ILs as you have done in the graphs. i.e. Th2 (IL-4, IL-5, IL-9, IL-33), Th17 (IL...

Line 47: Require details for cyctokine measurement - any processing of samples? volumes?

Line 51: WBC should be written out in the first instance

Lime 53: what is the 'normal range'?

Line 54: CRP should be written out in the first instance

Line 54: Change "...good response to..." to "...responded well to..."

Line 54: How did it respond well?

Line 65: What two points was IL-67 not detected? Capital 'L' in 'IL-6'

Line 74: "...clearly decreased over time"

Line 75: "...did not show this decrease."

Lines 89, 91, 96: Rickettsia is a genus name and should be italicized

Line 93: Capital letter for 'Rikettsia'

Line 94-5: Recommend "...Th1 cells in order to attack R. japonica."

Line 106: "...specific past history and clinical course..." I do not fully understand this sentence, may need some clarification/rewritting

Line 111: Suggest "...and this may be linked to the decrease in eosinophils."

Statistical information would be benificial here. Are the changes seen in cytokines statistically significant? Adding values in the results would be useful (ranges of values on days 1 versus days 14). Figures and texts should be able to stand separate.

Figure legends are written as more descriptive text rather than actual legends.

Author Response

                  Responses to the comments of Reviewer #1

Comments to the Author
The authors describe the immune response to Rickettsia japonica infection in seven patients. This manuscript is well written and clearly laid out with minor errors. There are a number of corrections that could be made along with clarification regarding some of the data and protocols.

1)   ＊Throughout the text there are a number of spaces missing between words and numbers (for example line 36 "... 4 females from70 to 87..." requires a space between 'from' and '70': "... 4 females from 70 to 87..."

Response: We have corrected errors throughout the text. Thank you for pointing out.

2)   ＊Line 25: suggest change "...infection has been..." to "...infection was..."

Response: Thank you for suggesting a grammatical error. We corrected it.

3)   ＊ Line 27: "...chilling..." correct to "...chills...

Response: We have corrected it.

4)   ＊ Line 28: "...days following a tick bite."

Response: We have changed the sentence as you said.

5)   ＊ Line 29: Need definition for "DIC"

Response: Thank you for your suggestion. We described the definition of DIC in the text.

6)   ＊Line 30: The sentence starting "Therefore, this worsening..." is not clear. Suggest an alternative sentence such as "Therefore, the deterioration of symptoms following a JSF infection needs to be understood." or similar.

Response: We followed your suggestion.

7)   ＊Line 39: What PCR was used? please reference

Response: We added PCR method as a reference.

8)   ＊Line 40: What ELISA/IFA assay was used? Please reference or explain

Response: We explained ELISA/ IFA assay in the text.

9)   ＊ Line 42-43: Serum samples were also collected on days 3 and 7 for cases 1-3

Response: We added the sentence in the text.

10)   ＊ Line 43: delete "the": "...-80C before use."

Response: We agree with your assessment. We deleted it.

11)   ＊ Line 44: I would recommend grouping the ILs as you have done in the graphs. i.e. Th2 (IL-4, IL-5, IL-9, IL-33), Th17 (IL...

Response: Thank you for your suggestion. We have done it.

12)   ＊ Line 47: Require details for cyctokine measurement - any processing of samples? volumes?

Response: We described the details.

13)   ＊ Line 51: WBC should be written out in the first instance

Response: We described it in materials and methods section.

14)   ＊ Lime 53: what is the 'normal range'?

Response: We have deleted the term.

15)   ＊ Line 54: CRP should be written out in the first instance

Response: We described it in the materials and methods section.

16)   ＊ Line 54: Change "...good response to..." to "...responded well to..."

Response: We changed the sentence.                                                  

17)   ＊ Line 54: How did it respond well?

Response: We have modified the text.

18)   ＊Line 65: What two points was IL-67 not detected? Capital 'L' in 'IL-6'

Response: Two points were day 1 and day 14. We have changed it. We are sorry about miss spells. We modified them.

19)   ＊ Line 74: "...clearly decreased over time"

Response: We changed the sentence.

20)   ＊ Line 75: "...did not show this decrease."

Response: We changed the expression, too.

21)   ＊ Lines 89, 91, 96: Rickettsia is a genus name and should be italicized

Response: We made corrections.

22)   ＊ Line 93: Capital letter for 'Rikettsia'

Response: rickettsia japonica was changed to R.japonica.

23)   ＊ Line 94-5: Recommend "...Th1 cells in order to attack R. japonica."

Response: We changed the sentence according to your advice.

24)   ＊ Line 106: "...specific past history and clinical course..." I do not fully understand this sentence, may need some clarification/rewritting

Response: We rewrote the sentence. We think readers can understand easily.

25)   ＊ Line 111: Suggest "...and this may be linked to the decrease in eosinophils."

Response: We have changed the sentence following your suggestion.

26)   ＊ Statistical information would be benificial here. Are the changes seen in cytokines statistically significant? Adding values in the results would be useful (ranges of values on days 1 versus days 14). Figures and texts should be able to stand separate.

Response: We appreciated your suggestion. Statistical figure is similar to Figure 2, therefore we have supplemented the statistical information in Figure 2.

27)   ＊ Figure legends are written as more descriptive text rather than actual legends.

Response: We have modified figure legends as the reviewer 1 suggested.

Author Response File: Author Response.pdf

Reviewer 2 Report

In this article, “Transition of serum cytokine concentration in Rickettsia japonica infection,” the authors analyzed blood cells and the amount of cytokines in Rickettsia japonica infection and found elevated IFNg and IL-6 and decreased eosinophils. They discuss the possibility of a correlation between changes in IFNg and IL-6 and eosinophils. This report contains useful information and may also have implications for therapeutic treatment. However, I think the following points need to be corrected.

The methods for identification and counting of WBC, neutrophil, and eosinophil should be included in the materials and methods section.

The authors should cite a paper regarding the effects of IL-6 and IFNg on macrophages and Th1 cells in Line 93.

The authors should cite the previous report mentioned in line 97.

Author Response

Responses to the comments of Reviewer #2

Comments to the Author
In this article, “Transition of serum cytokine concentration in Rickettsia japonica infection,” the authors analyzed blood cells and the amount of cytokines in Rickettsia japonica infection and found elevated IFNg and IL-6 and decreased eosinophils. They discuss the possibility of a correlation between changes in IFNg and IL-6 and eosinophils. This report contains useful information and may also have implications for therapeutic treatment. However, I think the following points need to be corrected.

1)   ＊ The methods for identification and counting of WBC, neutrophil, and eosinophil should be included in the materials and methods section.

Response: We described the above information in Materials and Methods section.

2)   ＊ The authors should cite a paper regarding the effects of IL-6 and IFNg on macrophages and Th1 cells in Line 93.

Response: We have supplemented the references.

        
3)   ＊The authors should cite the previous report mentioned in line 97.

Response: We have added the previous report as reference.

Author Response File: Author Response.pdf