All reviews of published articles are made public. This includes manuscript files, peer review comments, author rebuttals and revised materials. Note: This was optional for articles submitted before 13 February 2023.
Peer reviewers are encouraged (but not required) to provide their names to the authors when submitting their peer review. If they agree to provide their name, then their personal profile page will reflect a public acknowledgment that they performed a review (even if the article is rejected). If the article is accepted, then reviewers who provided their name will be associated with the article itself.
Thank you for your comprehensive revision and detailed point-by-point responses. I have carefully reviewed the rebuttal letter and the revised manuscript, and I confirm that all reviewer comments have been fully and satisfactorily addressed.
You have substantially strengthened the methodological clarity, expanded the Methods and Discussion sections with the required details, incorporated the suggested immunological and clinical distinctions, added the necessary references, and refined interpretational language where needed. All requested additions—such as clarification of diagnostic criteria, expansion of clinical characteristics, incorporation of EAACI hypersensitivity classification, and distinction between IgG-mediated and non-IgE-mediated pathways—have been appropriately integrated.
All reviewers have now recommended acceptance, and the manuscript has been significantly improved.
I am pleased to accept your manuscript for publication.
Congratulations, and thank you for your careful work throughout the revision process.
[# PeerJ Staff Note - this decision was reviewed and approved by Valeria Souza, a PeerJ Section Editor covering this Section #]
The author has effectively responded to all reviewer comments.
No comment
No comment
The text is clear and written in unambiguous, correct English grammar.
The bibliographic references are sufficient, and a transparent background is provided.
The article structure, figures, and tables are presented professionally.
The research fits the Aims and Scopes of the Journal
The Research question is well defined, relevant, and meaningful, stating how research fills the identified knowledge gap.
The paper describes a rigorous investigation performed to a high technical and ethical standard.
The methods are described with sufficient detail and information to replicate.
All underlying data have been provided; they are robust, statistically sound, and controlled.
The authors are self-contained in their conclusions, presenting relevant results to support their hypotheses.
Conclusions are well stated, linked to the original research question, and limited to supporting results.
The authors complied with all reviewers' suggestions, and the paper is ready to be published.
No remarks, as previously
No remarks, as previously
No remarks, as previously
My comments have been properly addressed and thoroughly elaborated on. The author has addressed the possibloe aspects and contexts of the interpretation of their results. I agree and appreciate their openness for the discussion of the findings and for the agreement to more cautious and toned dwon interpretation of the results' significance. I congratulate on this work, which is a valuable, interesting and possibly inspiring addition to the current state of knowledge regarding allergic rhinoconjucntivitis.
**PeerJ Staff Note:** Please ensure that all review, editorial, and staff comments are addressed in a response letter and that any edits or clarifications mentioned in the letter are also inserted into the revised manuscript where appropriate.
**PeerJ Staff Note:** PeerJ's policy is that any additional references suggested during peer review should only be included if the authors find them relevant and useful.
**Language Note:** When preparing your next revision, please ensure that your manuscript is reviewed either by a colleague who is proficient in English and familiar with the subject matter, or by a professional editing service. PeerJ offers language editing services; if you are interested, you may contact us at [email protected] for pricing details. Kindly include your manuscript number and title in your inquiry. – PeerJ Staff
This study investigated the role of fungus-specific IgE and IgG antibodies by analyzing serum samples from 40 patients with allergic conjunctivitis and 20 healthy controls. The findings revealed significantly elevated levels of both antibody types in patients, with IgG levels notably higher than IgE across four common fungi. IgG levels showed stronger correlations with skin prick test positivity and clinical severity scores, suggesting that fungus-specific IgG may serve as a reliable biomarker for disease severity.
The experimental design used in this study is generally sound and appropriate for the research objectives. However, further clarification is needed in the methods and data collection sections, particularly regarding how patient histories were obtained, what inclusion and exclusion criteria were applied, and whether standardized procedures were used for collecting immunological and clinical data. Providing these details would enhance the transparency and reproducibility of the study.
-
Methods
1. Lines 97-98 ‘The allergic group consisted of 40 patients 98 (14 males and 26 females; mean age: 25.2 ± 16.4 years) diagnosed with perennial allergic’
How does the author differentiate perennial allergic conjunctivitis from other forms of allergic conjunctivitis in terms of clinical presentation, allergen exposure, and immunological markers?
2. Line 99 ‘The control group comprised 20 healthy…….’
What is the rationale behind the author's selection of a smaller number of healthy controls (n=20) compared to patients with perennial allergic conjunctivitis (n=40) in the study design?
3. In the methods section, it would be beneficial for the author to clarify whether a detailed history of allergic conditions was obtained from the patients, along with relevant demographic data. Additionally, it would be better to mention whether visual acuity, refractive status, and other eye examinations were assessed.
Results
The results section would be more informative if it began with an overview of the participants' demographic characteristics, including age, gender distribution, duration of symptoms, and history of allergic conditions. Highlighting the differences in these features between the two groups would help contextualize the findings and enhance the interpretation of the clinical data presented.
Discussion
Some of the references cited in this section are relatively outdated, having been published in 2001 and 2003. It would be beneficial to update this section by incorporating more recent and relevant studies to ensure the discussion reflects current knowledge and advances in the field.
The manuscript is clear and well-structured.
Use consistent units and symbols (mm, KU/L), italicize species names, and standardize brand names with manufacturer/city/country once.
Clarify meibomian gland “normal” criteria and methods; define Schirmer I procedure and cutpoints.
-
The manuscript implies diagnostic superiority and pathophysiologic mechanisms (Th1 dominance, barrier dysfunction) from correlations alone. Temper language to association, not causation. Move mechanistic inferences to “hypothesis-generating.” If claiming diagnostic utility, add ROC analyses (AUC, DeLong tests), optimal thresholds (Youden index) with internal validation (bootstrap or k-fold).
Most physicians think "inside the box" of the IgE-mediated hypersensitivity mechanisms when diagnosing patients with allergic conjunctivitis. However, the Precision Medicine concept is trying to modify this trend by adding resources and new concepts to incentivize physicians to endotype phenotypic diagnoses, such as the non-IgE-mediated allergic conjunctivitis, helping the prescription of eviction strategies and resolutive treatments such as allergen desensitization.
The scientific community has given its first pass to recognize the contribution of the non-IgE-mediated hypersensitivity mechanisms with ex vivo tests such as the Leukocyte Adherence Inhibition Test. For example, my group has published papers on diagnosing CELL-MEDIATED hypersensitivity against fungi. However, this IS NOT the case with the paper in question, which approaches the HUMORAL mechanisms of hypersensitivity (IgG-mediated)
Olivier, C. E.; Pinto, D. G.; Teixeira, A. P. M.; Santana, J. L. S.; Santos, R. A. P. G.; Lima, R. P. S.; Monteiro, E. S., Contribution of the Leukocyte Adherence Inhibition Test to the Diagnosis of Innate Non-IgE-mediated Immunoreactivity against Alternaria alternata. Asian Journal of Immunology 2023, 6 (1), 243-251.
Olivier, C. E.; Pinto, D. G.; Teixeira, A. P. M.; Santana, J. L. S.; Santos, R. A. P. G.; Lima, R. P. S.; Monteiro, E. S., Contribution of the Leukocyte Adherence Inhibition Test in Diagnosing Non-IgE-Mediated Immunoreactivity against Aspergillus fumigatus in Patients with Allergic Rhinitis and Asthma. Asian Journal of Immunology 2024, 7 (1), 12-20.
The authors should focus on the non-IgE-mediated hypersensitivity mechanismsAllergic, and for this, the recognition of the modern Hypersensitivity classification according to the EAACI position paper is crucial:
Jutel, M.; Agache, I.; Zemelka-Wiacek, M.; Akdis, M.; Chivato, T.; Del Giacco, S.; et-al, Nomenclature of allergic diseases and hypersensitivity reactions: Adapted to modern needs: An EAACI position paper. Allergy 2023, 78 (11), 2851-2874.
**PeerJ Staff Note:** It is PeerJ policy that additional references suggested during the peer-review process should only be included if the authors are in agreement that they are relevant and useful.
-
-
Allergic fungal sensitization in patients with allergic conjunctivitis is a medical conundrum due to the lack of resources and tools to diagnose this condition.
This work is essential to clarifying and reinforcing the diagnosis of humoral non-IgE-mediated fungal allergic conjunctivitis for helping patients suffering from this condition.
Once diagnosed, eviction and desensitization strategies may be implemented to resolve the allergic disease. This must be put in perspective.
These aspects of the manuscript are correct, and I do not have anything to reproach from the point of view of the reporting quality. Results are well addressed in the goals of the study, and they are accordingly reflected in the discussion.
The design and planning of the study are correct, methods are described accordingly.
The results are original and intriguing, and analyses have been performed with the use of appropriate and well-selected statistical tools.
I do have some objections and suggestions regarding the discussion and interpretation of results. As it is well known and highlighted in the manuscript, IgG reflects the previous exposure to a given antigen, and its presence is a hallmark of the immune response elicited by that exposure. It is interesting that the authors associated the presence of IgG with the SPT positivity rate, given that SPT reflects rather an IgE-mediated sensitization. Could this be possible that both positive results, i.e., IgG in serum and SPTs, coincide, due to the fact that higher and more frequent exposure may increase the probability of sensitization? This can be a logical interpretation, and in my opinion, this possible mutual dependence (or even coincidence) has not been clearly indicated in the discussion as a possible explanation of the results obtained in this study. If that is to be considered, the pure and straightforward association of IgG with positive SPT may seem overrated and given too much significance. Another important aspect of the findings, especially in the context of rhinitis and CRS with polyops, may be that - in the Asian population - the frequency of non-eosinophilic polyps, presumably less associated with type 2 inflammation, is much higher, as compared with the European population, where eosinophilic polyps predominate. I suggest that this possible explanation be considered in the discussion, and the authors may wish to place it in the context of the results.
All text and materials provided via this peer-review history page are made available under a Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.