Advances in the Clinical Application of Histamine and Diamine Oxidase (DAO) Activity: A Review

Round 1

Reviewer 1 Report

Tan et al. have reviewed the available literature on expression levels of diamine oxidase (DAO) in different diseases or medical conditions, and how this information is/can be applied in a clinical setting. There are many studies/papers where the role of DAO has been investigated in different diseases, and the authors of this review have done a good job in collecting the information from a good number of current and relevant references into a clear, comprehensive and well-structured overview. This work is also relevant and of interest to the field, since there are no recent reviews on this topic. The statements and conclusions drawn by the authors are coherent and supported by the listed citations.

My main concern regarding this review is the scope. I am not entirely sure that Catalysts and the special issue “State-of-the-Art in Enzyme Inhibitors” is the correct journal for this type of review. It might work in Catalysts, but there is very limited information on inhibitors and the development of inhibitors against DAO that would justify publishing this review in the special issue “State-of-the-Art in Enzyme Inhibitors”. I would consider this review to be more suitable for example in Journal of Clinical Medicine (ISSN: 2077-0383; https://www.mdpi.com/journal/jcm), or potentially in Diagnostics (ISSN: 2075-4418; https://www.mdpi.com/journal/diagnostics).

Specific comments:

-       The title is short and concise; however, it is a bit too general so the reader might expect to get other types of information out of it. Please consider changing the title to a more precise and better description of the content of the review.

-       Section 3, line 267 – “…so effective measures must be taken to prevent”. To prevent what exactly?

-       Section 5, line 318 – “…radioactivity assays, the accurate and reliable ELISA…” Add an “and” after the comma or split the sentences: “…radioactivity assays. The accurate and reliable ELISA…”

-       Section 6, line 344 – “…is challenging, the high economic…” Add an “and” after the comma.

-       Section 6, line 346 – “…clinical practice. and routine analysis…” Remove “and” and put capital R for routine.

-       Table 1, pregnant – Change “pregnant” to “pregnancy” and change confirm (“Serum DAO has a role in pregnancy confirm and screening…”) in the comments to “confirmation”.

-       Table 1, liver disease – Change the order and correct spelling mistake in the comments: “DAO might be a potential biomarker in patients with liver and intestinal dysfunction.”

-       Table 1, histamine intolerance – Remove great from the comments and correct some language mistakes: “The role of DAO in diagnosis and treatment of histamine intolerance has been clarified”.

-       Table 1, footnote, line 351 & 352 – What does the footnote refer to? I can’t find the ¹ anywhere in the text or the table. Also change “researches” to “research”.

Author Response

Dear Reviewer 1:

We sincerely thank you for your valuable comments that we have used to improve the quality of our manuscript previously entitled “Characterization and Applications of Diamine Oxidase (Manuscript ID: catalysts-1984573)” in Catalysts. We have made extensive modifications to our manuscript, and changes/additions to the manuscript are given in the blue text.

Comment 1:

My main concern regarding this review is the scope. I am not entirely sure that Catalysts and the special issue “State-of-the-Art in Enzyme Inhibitors” is the correct journal for this type of review.

Answer 1:

Thanks for your kind reminders. We submitted the present manuscript to this journal after much deliberation. As we know, Catalysts (ISSN 2073-4344) is an open-access journal, focusing on the latest research findings in the field of catalytic reactions, catalyst preparation and applications. And for the DAO, as a hot intracellular enzyme, is closely related to the synthesis of nucleic acid and protein in mucosal cells, which can reflect the integrity and damage degree of various disease. In recent years, a number of studies have found that a variety of drugs and food could produce significant inhibitory effects on it, resulting in significant histamine intolerance (HIT) and even histamine poisoning symptoms (mentioned in section 3 and section 4). To sum up, we think this article might be suitable for this journal.

Comment 2:

For all the specific comments listed.

Answer 1:

All changes/additions are given using the “track changes” function in the modified version.

After discussion, we change the title “Characterization and Applications of Diamine Oxi-dase” into “Advances in the clinical application of histamine and diamine oxidase (DAO) activity: a review”; in Section 3 line 267 (now in line 271), we have insert “so effective measures must be taken to manage these patients” instead of “to prevent…”; As for the other language and spelling problems you mentioned, we have made relevant revisions and marked them in the manuscript. And you mentioned the Table1 footnote ”¹”, We are very sorry that footnote in line 351 (now in line 384) was a mistake, It's an illustration of the Table1.

Thank you for your consideration of our manuscript. We hope that the revisions in the manuscript and our accompanying responses will be sufficient to make our manuscript suitable for publication in Catalysts.

Best wishes，

Zhaowang tan, Yingwei Ou, Sheng Ang Zhou et al.

Reviewer 2 Report

In the manuscript, the authors provide an overview of the occurrence of the enzyme diamine oxidase (DAO) under various physiological and pathophysiological conditions. Among other things, they summarize how DAO levels in the organism vary in different diseases.

Overall, the manuscript is well written. However, before publication, the point 5 "Laboratory methods for quantitative measurements of DAO concentration in serum" should be completed: 

In this section, the authors describe that diagnostic studies focus, among other things, on the determination of DAO activity in serum. They also mention various analytical methods for doing this. Completely forgotten to discuss is the fact that DAO is actually not present in the serum under normal circumstances. The enzyme primarily responsible for the degradation of amines such as histamine in serum is rather plasma amine oxidase (PAO), also called vascular adhesion protein-1 (VAP-1) or amine oxidase copper containing 3 (AOC3) (see e.g. Feurle and Schwellenberger, Plasma amine oxidase has a broad substrate specifity and efficiently converts histamine. Inflamm. Res. 56 Suppl 1 2007 S55-S56). This enzyme is closely related to DAO, which is also known as AOC1. Both enzymes have copper and the cofactor topaquinone in the active site. This explains that both enzymes convert the same substrate amines in part, such as histamine and also putrescine (see above mentioned reference and Mergemeier et al., Anal. Biochem. 2018, 549, 29-38). Thus, the problem arises that the DAO activity in serum is not determined correctly because the activity of PAO is measured at the same time. This should be discussed. One substrate that is often used in DAO activity assays beside histamine and putrescine is cadaverine (see Garcia-Martin et al. Clinical Biochemistry 2007, 40, 1339-1341). This compound could be a selective substrate for DAO over PAO. However, I could not find a reference demonstrating this. Perhaps the authors know of such a reference. This should then also be cited. Otherwise, the assays with cadaverine should also be critically discussed.

Author Response

Dear Reviewer 2:

We sincerely thank you for your valuable comments that we have used to improve the quality of our manuscript previously entitled “Characterization and Applications of Diamine Oxidase (Manuscript ID: catalysts-1984573)” in Catalysts. We have made extensive modifications to our manuscript, and changes/additions to the manuscript are given in the blue text.

We thank you for pointing out this issue, we indeed should have spotted these mistakes much earlier. In accordance with your suggestions, we have revised and resubmitted the article to address some of the issues you raised on formatting, content etc. Besides, we have also discussed and made our own assumptions about whether DAO is present in normal healthy human serum in Section 5 Line 347-358. And we have found and discussed some of the few papers on the role of cadaveric amines as substrates in the determination of DAO in Line 360-365. We also think that more researches need to be explored.

Once again, thank you very much for your comments and suggestions for our manuscript.

Best wishes，

Zhaowang tan, Yingwei Ou, Sheng Ang Zhou et al.