Polyglandular Autoimmune Syndrome Triggered after CTLA-4 and PD-1L Immunotherapy Treatment

Round 1

Reviewer 1 Report

Overall, the manuscript is well written and the study well conceived. Methods are clearly illutrated, findings are of some interest, the topic is intriguing. However, it seems the paper lacks to mention the role of some antibodies that can stop these checkpoints. further, alternative or complementary pathway to that of immunological checkpoint do exist and it could be reported. Please consider citing seminal papers in this field:

PMID: 31697586

PMID: 30348222

Author Response

Dear reviewer:

Thank you very much for your time and suggestions. The pathophysiological basis of classical and other alternative of immune check points (such as LAG-3) are very interesting and there are extensive studies for pharmacological application (Maruashi et al, 2020; 32929051).

Despite this, today the points with clinical use in oncology are PD-1, PD-1L and CTLA4, which are the ones on which I have focused this case report. Undoubtedly, other parallel pathways could be explored and possibly useful at clinical level but the essence of the article in “case report” format has made me be straightforward in my approaches and not look into the wide options that can be provided.

I have read with interest both references and those research lines have suggested me ideas for future collaborations in that direction.

Thank you in advance.

Kind regards:

Reviewer 2 Report

Following are my concerns.

• Paper describes only a single case and in few pages, so in my opinion, it may not be suitable for a full paper. Instead, it can be published as letter to the editor, minireview or communication to the journal or mini paper.
• There were only 9 references and that only one reference is in 2016, rest of the references are old. Authors should include few more recent references ranging from 2015 to 2020. (Of late there are several publications regarding adverse or autoimmunity arising out of immunotherapy)

Author Response

Dear reviewer:

Thank you very much for your comments.

As you can see, I tried to give to this article the format corresponding to a classical "Case Report", understanding the limitations that this format has. Even so, I guess its contribution is interesting because of the didactic capacity that it has explaining molecular mechanisms that its difficult for clinician to handle.

Moreover, I think it has an extra interest because of the unusual fact that up to three autoimmune diseases occur in such a shortened period in the same patient after the beginning of said treatment, something not previously found in literature. It brings the idea that in these patients, an autoimmune disease triggered by these treatments could come hand in hand with others, something that clinicians should be warned.

I agree with you that some updated references instead classical ones could bring an extra, something that you can find in the novel version of the article recently sent.

Thank you in advance.

Kind regards:

Juan