Round 1

Reviewer 1 Report

This manuscript titled:  Update on desensitization strategies and drugs on hyperimmune patients for kidney transplantation by Salvadori, M is a review on desensitization strategies for highly sensitized patients awaiting kidney transplantation.  The review included discussion of drug targets use for desensitization: B-cells, plasma cells, antibodies and complement.  

The manuscript included useful tables: Table 1 -- summarizes available assays; Table 2 summarizes pharmacologic option; Table 4 summarizes results of patients treated with anti-CD38.  However, the English was difficult to understand and to follow. 

Suggestion: Pg 14, line 289 stated: to date, C1INH is only used in preliminary results of ABMR treatment, but it is not yet used as prophylaxis.  Please refer to a reference (and revise the above statement accordingly): A phase I/II placebo-controlled trial of C1-inhibitor for prevention of antibody-mediated rejection in HLA sensitized patients. Transplantation 2015 Feb;99(2):299-308.  In this study, the authors reported that C1-INH resulted in significant elevations of C1-INH levels, C3, C4, and reduced C1q+ HLA antibodies and that the combination of antibody reduction and C1-INH may prove useful in prevention of AMR. Further controlled studies are warranted.

 

 

The below are a few examples of grammatical errors noted:

Pg 1, line 21: in-complete sentence in Abstract: “However is to date possible to desensitize many patients and to obtain successful transplantation.”

Pg 2, line 45: in-complete sentence: “Plasmablasts migrate to bone marrow were generate long-lived plasma cells that migrate to survival niches under the effect of PAMP [6,7]. “

Pg 2, lines 50-52: run on sentence: “With different techniques is now possible to detect both the alloreactive serological memory and the alloreactive cellular memory in patients waiting for kidney transplantation so to stratifying the humoral and cellular risk of candidates to a solid organ transplantation [10].”

Pg 2, lines 55-56: replace the period with a comma after flow cytometry [15]. Elispot assay….  

Pg 6, lines 123-124: change the word “removal” of IgG  to reword the sentence “ IA is the preferred methods due to its ability to efficiently remove IgG”.

Author Response

C1-INH has been reworded as suggested and the reference added

English wording has been carefully controlled and modified with the help of a colleague of english lenguage. In addition to the points suggested many others have been rewritten

Reviewer 2 Report

See comments in the loaded file

Comments for author File: Comments.docx

Some minor typings need review

Author Response

A paragraph has been added to better explain the functio of FcgammaRIIB and a reference added

References have been added to table 3 and 4

A paragraph has been added with the requested references (Jordan, Kjellmam)

A paragraph on belatacept action has been added, with three more references

Reviewer 3 Report

The manuscript “Update on desensitization strategies and drugs on hyperimmune patients for kidney transplantation” by Maurizio Salvadori comprises a literature review on desensitization strategies in kidney transplantation. The review addresses an important aspect of current limitations in transplantation in general. I do not have specific concerns except that the English requires moderate editing as the formulations sometimes are misleading.

See resonse to author.

Author Response

Thank you for appreciating my study

English wording has been extensively corrected 

Round 2

Reviewer 1 Report

Revised manuscript is much improved.  Accept.