Expansion of Rare and Harmful Lineages is Associated with Established Rheumatoid Arthritis
, Patricia Ruiz-Limón 1,3,†, Isabel Moreno-Indias 1,3,4,*, Sara Manrique-Arija 1,2, Francisco J. Tinahones 1,3,4 and Antonio Fernández-Nebro 1,2,5Round 1
Reviewer 1 Report
The authors in this article entitled “Expansion of Rare and Harmful Lineages is Associated with Established Rheumatoid Arthritis” showed the microbial and bacterial load and its effect during RA in patients. This clinical study with short group of people showed promising results in microbiome environment along with others. The way of data representation is promising too. I recommend this article for publication in current format with best my best wishes. In future study, it will be impressive if the authors can add more patients data.
Author Response
Comments for the reviewers
Reviewer #1:
Dear Reviewer #1. We appreciate your commentaries. In future study, we will try to add more patients data.
Reviewer 2 Report
The manuscript entitled “Expansion of Rare and Harmful Lineages is 2 Associated with Established Rheumatoid Arthritis” is an interesting study focused on a hot topic. It is well-written.
I have only few comments.
It is not clear to me, why authors reported figure 1C in the panel of figure 1. Since figure 1C is cited after in the text (in another section of the results), it should be reported in figure 2 in order to be clearer.
Figure 1 legend: “ANOSIM p=0,070” should be corrected to ANOSIM p=0.070.
In table 1, there are some parts highlighted in yellow, why?
In table 1, there is a p-value in bold, why?
Figure 2C: could the authors align the three graphs? The one in the center is higher compared to the other two.
Figure 3: could the authors use the same style for all the graphs?
Table 2: could the authors use the full stop as decimal separator instead of the comma?
Could the authors use italics when appropriate in the figures?
Could the authors submit figures with higher quality?
Author contribution are missing at the end of the manuscript and funding, which is empty, are reported in the Acknowledgments.
Author Response
Dear Reviewer 2. Thanks for your comments. Please find here our replies for them. We accepted all your suggerences.
- It is not clear to me, why authors reported figure 1C in the panel of figure 1. Since figure 1C is cited after in the text (in another section of the results), it should be reported in figure 2 in order to be clearer.
Reply: Following the recommendation offered by the Reviewer, we have presented the figure 1C such as figure 3 instead of figure 2 for reason of space. This new information has been included in the revised figure and in revised version of the manuscript, page 5, line 161. Below, we detail the modification in the text:
“Interestingly, at the species level we identified a significant increase in the abundance of Collinsella aerofaciens (p=0.039) and a significant decrease in Dorea formicigenerans (p=0.044) in RA patients than in controls (Figure 3)”.
- Figure 1 legend: “ANOSIM p=0,070” should be corrected to ANOSIM p=0.070.
Reply: We apologize for these oversights and it has been corrected accordingly in the revised figure and in revised version of the manuscript, page 5, line 170-171.
- In table 1, there are some parts highlighted in yellow, why?
Reply: The authors apologize for this mistake in format. The yellow highlight has been removed (page 4, table 1).
- In table 1, there is a p-value in bold, why?
Reply: The authors apologize for this mistake in format. The p-value in bold has been removed (page 4, table 1).
- Figure 2C: could the authors align the three graphs? The one in the center is higher compared to the other two.
Reply: We apologize for this error and it has been corrected accordingly in revised figure and in revised version of the manuscript, page 6.
- Figure 3: could the authors use the same style for all the graphs?
Reply: The figure 3 has been changed to figure 4 and the style of graphs has been modified. The graphs are in revised figure and in revised version of the manuscript, page 7. Below, we detail the modification in the text:
“Lipid biosynthesis proteins” were significantly more frequent in controls than in RA patients (p=0.049) (Figure 4A).”
“Higher levels of this gene were found on RA patients (p=0.0041) (Figure 4B).”
“Our results show that the levels of the arginine deiminase gene were higher in RA patients (27985.97 copies) than in controls (16361.64 copies) (Figure 4C)”.
“… highly contributed to the difference in gene counts between RA patients (33.71%) and controls (20.75%) (Figure 4C).”
“…zinc transport system substrate binding-protein to be significantly less frequent (p=0.039) in RA patients than in controls (Figure 4D).”
- Table 2: could the authors use the full stop as decimal separator instead of the comma?
Reply: The authors apologized for this mistake. We have changed the comma for the full stop as decimal separator (page 8, table 2).
- Could the authors use italics when appropriate in the figures?
Reply: We apologize for these typographical errors. These have been corrected accordingly in figures 2B, 2C, 3 and 4C in the revised figure and in revised version of the manuscript, in pages 6, 7 and 8 respectively.
- Could the authors submit figures with higher quality?
Reply: We apologize for the quality of the images and thank the Reviewer for her/him constructive critique. Accordingly, we have modified the quality of figures.
- Author contribution are missing at the end of the manuscript and funding, which is empty, are reported in the Acknowledgments.
Reply: Added author contribution at the end of the manuscript and we have modified funding and acknowledgments.
Author Contributions (page 11, line 370-376): NMV participated in the design of the study and carried out patient recruitment and data collection. PRL and IMI were a major contributor in performing laboratory determination and contributor in interpreting laboratory data. NMV and PRL were a major contributor in writing the manuscript and they were a contributor in analyzing and interpreting the patient data. SMA was a contributor in including patients and interpreting the patient data. AFN participated in the design of the study and major contributor in writing the manuscript. AFN and FJT were contributor in analyzing and interpreting the patient data. All authors read and approved the final manuscript.
Funding (page 11, line 377-384): This work was supported by FIS Grant PI18/00824 (Instituto Carlos III, Fondos FEDER) and “Fundación Andaluza de Reumatología” Grant PI17/00016. Grant for medical researchers of the “Fundación Española de Reumatología”. The research groups belong to the “Centros de Investigación en Red” [CIBERobn, “Instituto de Salud Carlos III”], and thanks for its support to the CIBER-Metagenomics platform, especially to Isaac Plaza and Pablo Rodríguez. P-RL was supported by a “Juan de la Cierva Formación" contract (Ministry of Economy, Industry and Competitiveness; FJCI-2016-28173). IM-I was supported by the “MS type I” program (CP16/00163) from the Instituto de Salud Carlos III cofounded by Fondo Europeo de Desarrollo Regional – FEDER.
Acknowledgments (page 11, line 385): “Fundación Española de Reumatología” for the translation of the manuscript.
