Polyneuropathy Associated with IgM Monoclonal Gammopathy; Advances in Genetics and Treatment, Focusing on Anti-MAG Antibodies
, Shirley D’Sa 3, Alexander F. J. E. Vrancken 1, Nicolette C. Notermans 1, Josephine M. I. Vos 4 and Monique C. Minnema 2
Round 1
Reviewer 1 Report
Please see the attachment
Comments for author File: 
Comments.pdf
Author Response
Point 1: "The increase in our knowledge of pathophysiology and genetic alterations in IgM gammopathies and its related polyneuropathies led to an increase of possible therapies…." The sentence does not read well.
Response: we have divided the sentence into two sentences.
Point 2: "We excluded case reports and only included articles with a full text availability which were written in English between 1980 and today". I suggest to put the actual date limit for the search.
Actually, the authors may add the following references:
- Visentin A. et al 2022, for an excellent description of the signaling pathways in B-Cell malignancies.
- Steck AJ 2021 , for an in-depth and well-illustrated review on the pathogenesis and treatment of the MAG neuropathy.
Response: we added a specific date concerning the literature period. We also added the two recommended references.
Point 3: "...may transform significantly more frequent to lymphoma…" should read frequently.
Response: we adjusted the error.
Point 4: "Specific IGH variable…" Explain abbreviation
Response: abbreviation has been explained.
Point 5: "...forming the major dense line (MPL)…" Replace with MDL
Response: MPL replaced with MDL.
Point 6: Line 277 replace superior by better
Response: superior replaced with better.
Point 7: Paragraph 291-297 could be deleted, as the review has its focus on the MAG neuropathy and the elements in this paragraph are too summarized to describe adequately the very diverse forms of antigangliosides mediated PNP.
Response: we agree with this point of view and deleted the paragraph.
Reviewer 2 Report
The review by van de Mortel et al. describes polyneuropathy associated with IgM monoclonal gammopathies, its genetics, anti-MAG antibodies, as well as current and possible future treatments. The review is interesting, very well written, up-to date, complete, very clear, useful. Publication is thus recommended.
Author Response
There have not been any points to respond to. We thank the reviewer for the review.
Reviewer 3 Report
The manuscript is well organized and well written review of pathogenesis and treatments for IgM-related PNPs; the authors have provided a comprehensive discussion about PNP subtypes, genetics and phenotypes, as well as interesting insight on previous trials and promising new treatments.
I would only add a few comments/change proposals:
page 2: row 60, risk of “development of” instead of “to”; row 61: repeated “development”
pag 3, row 128: in addition to ref n° 29, it might be also useful to discuss a recent work regarding the importance of del6q in the progression from MGUS to WM ( Garcia Sanz, BJH 2020)
page 4, row 142-3: of note, recent works have also highlighted technical aspects of MYD88 analysis in MGUS vs WM, also suggesting a possibile link between mutational levels and risk of progression (see Ferrante M, Diagnostics 2021)
Author Response
The manuscript is well organized and well written review of pathogenesis and treatments for IgM-related PNPs; the authors have provided a comprehensive discussion about PNP subtypes, genetics and phenotypes, as well as interesting insight on previous trials and promising new treatments.
I would only add a few comments/change proposals:
Point 1: page 2, row 60; risk of “development of” instead of “to”; row 61: repeated “development”.
Response: development to replaced with development to. Double development deleted.
Point 2: pag 3, row 128: in addition to ref n° 29, it might be also useful to discuss a recent work regarding the importance of del6q in the progression from MGUS to WM ( Garcia Sanz, BJH 2020).
Response: we included the article of Garcia Sanz et al and mentioned del6q as a possible second hit in the development of WM from IgM MGUS.
Point 3: page 4, row 142-3: of note, recent works have also highlighted technical aspects of MYD88 analysis in MGUS vs WM, also suggesting a possibile link between mutational levels and risk of progression (see Ferrante M, Diagnostics 2021).
Response: we included the article of Ferrante et al and highlighted the difference in mutation level between IgM MGUS and sWM.
We thank the reviewer for the review.
