The Role of Anti-DFS70 in the Diagnosis of Systemic Autoimmune Rheumatic Diseases

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

 

Abstract:

·      ANA is used without introducing the abbreviation.

·      DFS70 is used without introducing the abbreviation.

·      Authors mention DFS70 fluorescence pattern occurring during ANA analysis but do not state the method.

·      It would be important to mention in the abstract that most people showing aDFS70 ab are healthy individuals (Muro et al. 2008, Lupus).

·      The conclusion (last sentence) in the abstract is somehow not logical and is in no relation to the previous paragraph. Why is this important? Which classes of non-SARD diseases? What is the clinical consequence?

 

Introduction:

·      Line 45: immune tolerance needs to be introduced, especially B cell tolerance (central and peripheral). Further, which “disruptions” are referred to in this section?

 

General comments:

·      Line 97: The sentence about COVID-19 comes out of the blue. It doesn’t follow from the previous paragraph. Why should this information be important to the technical discussion about HEp2 tests?
If the authors want to highlight that COVID-19 might have led to a high number of “false positives” on HEp2 tests, they should re-phrase this.

·      Line 112: The authors describe that antiDFS70 is mostly found as IgG but can also occur as IgE referring to autoallergic reactions. It would be good to introduce earlier in the text that antibodies refer to IgG (usually in the field of autoimmune diseases).

·      Line 134: The authors mention natural protective antibodies. This needs more explanation. Usually natural (protective) antibodies belong to the class of IgM (natural IgM, nIgM). Natural IgG also exists targeting several self-molecules. Importantly, all natural antibodies share features such as polyreactivity/cross-reactivity and low antigen binding affinity.

Are the mentioned DFS70 antibodies IgG or IgM class?

·      Line 138 makes no sense. In the previous paragraph the authors describe the presence of DFS70 antibodies within a polyclonal pool of other autoantibodies and in the next sentence they describe “monospecificity” of DFS70 antibodies which refers to the reactivity and has nothing to do with polyclonality. This paragraph needs to be re-written with close attention to the nomenclature.

·      Line 169 mentions natural antibodies again, so please explain this term in the text.

Comments on the Quality of English Language

NA

Author Response

Dear reviewer,

Thank you for your work on reviewing our article and the suggestions you've provided.

Abstract:

Comments on the decryption of abbreviations have been taken into account, and the text has been corrected.

Information has been added indicating that the majority of patients with anti-DFS70 positivity are healthy.

Regarding the logic of the last sentence: information about other conditions where anti-DFS70 is detected is discussed in Section 4, "Assessment of Detecting DFS70 Antibodies in Clinical Practice," that is why fact is mentioned in that section. In other words, we present a diagnostic pathway: definition of ANA, next the detection of specific antibodies and the analysis of this information considering 1. clinical factors and 2. the understanding that elevated antibodies, especially DFS70 antibodies, may not be associated with other non-systemic rheumatological diseases or may indicate the absence of a systemic disease.

 

Introduction:

As our goals did not include a detailed analysis of the normal and pathological functioning of the immune system, we removed a part of the sentence, shifting the focus to the earlier appearance of antibodies in the blood and a positive ANA analysis. This fact should be critically analyzed by the physician, the presence of antibodies in the absence of disease symptoms cannot be a reason for "preventive" treatment but should draw the attention of the physician.

 

General comments:

• Line 97: Line 112:

Yes, in this case, we discussed an increase in false-positive tests after a previous COVID-19 infection. The sentence has been rephrased.

The relation of autoantibodies to IgG has been included in the text (line 80).

• Line 134, 138, 169

You are correct; we used an inappropriate definition in this sentence. The text has been reformulated to avoid possible misinterpretation.

Reviewer 2 Report

Comments and Suggestions for Authors

The reviewer would like to thank the authors for their immense efforts in compiling this review delineating the role of anti-DFS70 in diagnosing systemic autoimmune rheumatic diseases. Indeed, the review carries a lot of interesting facts from earlier studies, however, for the betterment of this work, the reviewer would like to recommend a few minor comments;

# Section 2 Line 53:
….despite recommendations, in our clinical practice, we may still encounter results obtained by solid-phase immunoassays.
- Is the statement based on the author's own studies? If not, please paraphrase the sentence and add references.
- Line 77-82: Add references against the statement where the authors incited the ACR and EULAR recommendations.
# Table 1 :
- Add references against each Pathological studies.

# Section 4 :
………… DFS70 antibodies are found in conjunction with other specific antibodies, whereas in healthy individuals and patients without SARDs, these antibodies are usually present in isolation, without any other autoantibodies. Therefore, the detection of monospecific DFS70 antibodies in blood serum is commonly associated with a low probability of developing SARDs [25].
-The reference against the statement could be more validated if the author added the reference to a specific research article that carried the work instead of a review article.

Section 5: Discussion
A discussion must be the section that carries the information or illustrations to validate the recent observations or results obtained with references to earlier works. Hence, references against each statement need to be included. Thus,
-Either the author states this section as a Conclusion of this review or includes references (if the author wants to keep the section as the Discussion.

 

Author Response

Dear reviewer,

Thank you for your work on reviewing our article and the suggestions you've provided.

Thank you for analyzing our work. All recommendations have been considered.

Section 2 Line 53:

This information was mentioned in various sources we analyzed, but upon reevaluation, we agree that different methods are currently rarely used, therefore, we removed this text, leaving only the information about the "gold standard of diagnostics."

Table 1 - all references are present in the preliminary text (line 57 - Each pattern is assigned an alphanumeric anticell code [1, 5 - 10] (Table 1).)

# Section 4  - This paragraph has been removed during the text correction.

Section 5: Discussion - The corrections have been made.

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

NA

Comments on the Quality of English Language

NA