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Article
Peer-Review Record

Characterization of Th2 Serum Immune Response in Acute Appendicitis

Int. J. Mol. Sci. 2026, 27(2), 733; https://doi.org/10.3390/ijms27020733
by Nuno Carvalho 1,2,*, Jani-Sofia Almeida 3,4,5,6,7,8, Elisabete Carolino 9, Francisco Lopes 1, Susana Henriques 1, João Vaz 1, Hélder Coelho 10, Paulo Rodrigues dos Santos 3,4,5,6,7,8, Manuel Santos Rosa 4,5,6,7,8, Luís Moita 11,12, Carlos Luz 1,2 and Paulo Matos da Costa 2
Reviewer 2:
Int. J. Mol. Sci. 2026, 27(2), 733; https://doi.org/10.3390/ijms27020733
Submission received: 5 November 2025 / Revised: 3 December 2025 / Accepted: 2 January 2026 / Published: 11 January 2026
(This article belongs to the Section Molecular Biology)

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Congratulations to the authors for their work. This is an interesting article that addresses an important gap by comparing systemic immune markers with previously demonstrated local Th2 activation. However, there are some aspects that need to be addressed in order to enhance scientific rigor.

The introduction is too long  and repetitive, with phrases that reiterate similar ideas. The results section is quite dense. Perhaps the authors would consider simplifying the presentation, grouping related parameters in the tables and summarizing key clinical patterns in order to improve readability. Also, each table repeats long sets of abbreviations which are not needed.

The discussion section should clearly state limitations of the study and try framing the findings in a more cautious way so that the results will not appear overstated given that we are dealing with a small study group and this a single center study.

There are some inconsistencies with the references regarding standard punctuation and spacing.

The conclusion is supported by the findings but could be strengthened by proposing clear steps for research.

Comments on the Quality of English Language

The article is generally well written and understandable, with correct scientific terminology and coherent structure. Most sentences are grammatically correct, and the overall flow is acceptable. However, minor issues related to phrasing, article use, punctuation, and repetition warrant editing.

Author Response

comment1: 

The introduction is too long  and repetitive, with phrases that reiterate similar ideas. The results section is quite dense. Perhaps the authors would consider simplifying the presentation, grouping related parameters in the tables and summarizing key clinical patterns in order to improve readability. Also, each table repeats long sets of abbreviations which are not needed.

Response:

The introduction was reformulated, with word count reduction and eliminating repetitive ideas.
The results section is in fact quite dense, we made an effort for simplifying, without losing clarity, which turned a heavy work.  Some results are presented as supplementary, if necessary, more tables can be presented as supplementary. 
The tables were reformulated, simplifying the lecture and reducing information, presented at the main text.

comment2:

The discussion section should clearly state limitations of the study and try framing the findings in a more cautious way so that the results will not appear overstated given that we are dealing with a small study group and this a single center study.

Response: Limitations were reinforced in the discussion section.

comment3:

There are some inconsistencies with the references regarding standard punctuation and spacing.

Response: The references punctuation and spacing were reviewed.

comment4:

The conclusion is supported by the findings but could be strengthened by proposing clear steps for research.

Response: Clear steps for research were proposed.

 

Reviewer 2 Report

Comments and Suggestions for Authors

The appendix, which is full of lymphoid tissue, is a peripheral organ of the immune system. In ruminants, it plays a major role in preserving the immune system's homeostasis; in humans, this role is diminished, but the appendix is assigned an important role in antibody formation. This enables us to view acute appendicitis as a "shock" organ of the development of allergic inflammation and as a hyperreaction of an immunocompetent organ to antigenic stimulation of the gastrointestinal tract's mucous membrane. A hypersensitive inflammation with necrosis of follicles and their destruction, hyperemia of the vessels of all layers of the appendix wall, involving various cells and inflammatory mediators, occurs very easily under conditions of sensitization in the lymphoid tissue under the influence of even small-power irritants, both specific and nonspecific in nature. Nevertheless, not enough research has been done on how allergies contribute to the pathophysiology of acute appendicitis. As a result, this paper satisfies the criteria for original research and is pertinent.

The low percentage of mentioned literature from 2020 to 2025 (only 25%) is one of the article's shortcomings, however this is an objective explanation given how uncommon study in this area has been lately.
The authors set out to investigate the role of the allergic component of inflammation in the pathogenesis of different types of acute appendicitis, including cases of appendectomy without obvious histological signs of leukocytic infiltration of the organ, based on early research that demonstrated the involvement of mechanisms (cells, cytokines, and immunoglobulins) in type 1 hypersensitivity reactions in acute appendicitis. The authors are able to address the research hypothesis thanks to the suggested study design.

It is feasible to repeat such a study with the availability of consumables, patients with acute appendicitis, trained physicians, and researchers, albeit there might be some differences because of the use of various manufacturers' reagents, different countries, and other circumstances.
We can evaluate the amount of cytokines and immunoglobulin E in the blood serum and understand the fundamentals of gating the major populations of lymphocytes in the peripheral blood and effector cells in patients with acute appendicitis thanks to the availability of illustrative material, both primary and secondary. Throughout the piece, the writers offer adequate commentary on the data.

Using both their own and other authors' research findings, the authors describe how Th2 contributes to the pathophysiology of acute appendicitis in situ and the lack of an allergic reaction at the systemic level.
The work was completed with consent from the ethics committee and in accordance with the Helsinki Declaration.

 

The work's shortcomings include:

  1. Line 41, 46 should have a gap between phrases;
  2. Line 173 should be removed because it is confusing;
  3. Statistically significant differences should be shown in the tables right after the data, rather than in a separate column that doesn't specify which groups this is disclosed between. However, the writers clarify it later in the article's text. However, the reader should be able to understand the illustrated material without having to read the writers' description of it;
  4. Class G immunoglobulin is important in allergic reactions, along with class E immunoglobulin. In this context, have the writers examined their part in the pathophysiology of appendicitis?

Author Response

comment1: Line 41, 46 should have a gap between phrases;

Response: A gap was introduced in Lines 41 and 46

comment2: Line 173 should be removed because it is confusing

Response: Line 173 was removed

comment3: Statistically significant differences should be shown in the tables right after the data, rather than in a separate column that doesn't specify which groups this is disclosed between. However, the writers clarify it later in the article's text. However, the reader should be able to understand the illustrated material without having to read the writers' description of it;

Response: The tables were reformulated, including the information required

comment4: Class G immunoglobulin is important in allergic reactions, along with class E immunoglobulin. In this context, have the writers examined their part in the pathophysiology of appendicitis?

Response: We are currently evaluating other markers of allergy in acute appendicitis, including IgG4

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