Role of the Immune System in Renal Transplantation, Types of Response, Technical Approaches and Current Challenges

Round 1

Reviewer 1 Report

This review is a comprehensive review, like a chpater of transplantation textbook. Just need some language editing and could be published.

Author Response

Thank you very much for your comments.

Reviewer 2 Report

The review is mainly focused on how immune system plays a major role in renal transplantation and the authors have described the different types of response against the graft and major part is focused on the different diagnostic tests that are available to characterize the donor/recipient interaction. The authors have done a good job explaining the methods and have provided nice pictorial representation of the same.

 

The title is a bit too long and it can be made concise.

 

Since the title is very broad  - The adaptive alloimmune response has always been considered as the main player and the role of innate immunity has been disregarded. The review will certainly bring in more readers if the authors want to include a section on how in the last decade there is a lot of evidence on how innate immune cells contribute to priming of the rejection machinery and control the activation of alloantigen-specific adaptive immunity. It can also provide a reader an insight on to how cross-talk between complement, coagulation and innate immune cells are carried out in kidney transplantation.

 

For the therapy section, instead of concentrating on the basic mechanisms involved in the diagnostic tests, addition of how these immunosuppressive regimen might influence the patients outcome or biological effects will help attract both researchers and clinical practitioners. Alloimmune risk stratification and donor/recipient characteristics will make the review stronger.

 

Perhaps even include some phase trials (ex: Tregs in minimizing immune suppression, 2020). It will make this review unique since there are a several 100 reviews explaining the same “technical approach”.

Author Response

Thank you very much for your comments.

We have included a section to explain the interconnection between innate immunity, the complement system and the blood coagulation system as well as the ability of innate immunity to modulate adaptive immunity. Line 139-165.

In the section on biological drugs we have included a clinical point of view.

We have included a paragraph stating that certain combinations of recipient and donor affect the outcome of transplantation and may increase the biological risk. Line 79-83.

We have commented on current therapies with regulatory T-lymphocytes and their potential to reduce immunosuppression (Line 730-754), and we have added a new figure explaining the main mechanisms of rejection and the immunorepressive function of T regs. (Figure 5).

Reviewer 3 Report

 

Abstract:

 Line 9,10: The sentence -The rate of mortality within the first year’s post-transplantation re-9 mains high, despite organ and tissue transplant has become in a widespread technique.

The authors mean more prevalent, or the meaning implied is not clear.

 Line 13-14 However, taking of biopsies is necessary to carry out this diagnostic test, with all the ensuing problems that brings to 14 immunosuppressed patients- Not clear and grammatically incorrect. Line 21-22: better adjustment of immunosuppressive therapies and hence to a more personalized medicine that improves the quality of life of 22 patients.

Consider rewriting the Abstract with correct terminologies.

Introduction:

Combine line 30-41 into a single paragraph.

The introduction section needs to be concise and need not have multiple paragraphs.

Fig 2A: Use unstained or not stained instead of no stain- and why is there no stainig can be mentioned

Line 509-510- The meaning from this statement is unclear

Author Response

Thank you very much for your comments.

We have rewritten part of the abstract.

We have deleted a paragraph from the introduction, which certainly provided redundant information about HLA and non-HLA antigens, but we have introduced another paragraph, explaining the increased risk of rejection and loss of transplant due to certain combinations of donor and recipient, at the request of another referee.

We have corrected figure 2a.

We have tried to clarify the paragraph that was not understood. (Line 5512-553).

Round 2

Reviewer 3 Report

Line 13: Change the 'taking of' biopsies to collection.

Fig.2 : change No stained to no stain

Table 2 heading and the table needs to start form the same page i.e. pg-13

Fig.4: check legibility of the text for Immuknow assay.

Line 599 Spelling of ImmuKnow assay is written as Immunoknow