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Two of the three reviewers of the original submission have examined the revised manuscript. Their concerns have been satisfactorily addressed with the revision.
[# PeerJ Staff Note - this decision was reviewed and approved by Vladimir Uversky, a PeerJ Section Editor covering this Section #]
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This manuscript has been improved as suggested by the reviewer
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I am absolutely satisfied with the modifications provided by the Authors and by the rebuttal they provided. This has indeed been a very fruitful and stimulating intellectual exchange of ideas, and the Authors have provided constructive replies. The amendments have been provided accordingly and appropriately, being correctly framed into the whole context of the article. As far as I am concerned, the manuscript is publishable after this revision, and I have no further issues to be raised.
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The paper is interesting and well written. The authors investigated the total IgE (tIgE) and specific IgE (sIgE) levels in 7,824 patients with suspected allergic diseases and identified the factors associated with allergic diseases. The study demonstrated that male gender, younger and older age groups, and the summer season were identified as significant predictors of allergic diseases based on tIgE levels.
I suggest discussing the role of Th17 cells, IL-31/IL-33 axis, vitamin D, microbiome, and sHLA-G molecules (see and add as references papers by Murdaca et al concerning Th17 cells, IL-31/IL-33 axis, vitamin D, microbiome, and sHLA-G molecules and immune responses, including autoimmunity and allergic diseases).
**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.
The methods and statistical analysis are consistent with the endpoints and well-defined.
The findings are useful for the readers and will increase the knowledge in the field.
The manuscript's writing style needs to be improved, such as:
Putting spaces between words. For example, line 36, please give space between disturbances (e.g., food allergy); lines 38, 39, 40, 43, etc., please give space before citation; line 110, please give space between SPSS and 26.0.
Please write consistently. For example, in writing numbers, 7824 or 7,824; 1334 or 1,334 (lines 115-116). Please choose which one is correct and write it consistently throughout the manuscript. You list food allergens after inhaled allergens in Figure 1, yet in Figure 2, the order is reversed. Please write consistently in the writing order. Lines 126 and 130, please write in the correct and consistent way to write male and female. Line 136, etc, please choose the common terms and write consistently throughout the manuscript whether you use the terms inhalant allergens or inhaled allergens, or inhalation allergens.
Line 74: 2-80C. The letter C in the manuscript is not the font of Times New Roman.
Lines 44-47: The sentence is too long; please separate it into a few sentences.
Lines 47-48: Though mechanistic understanding remains incomplete. Emerging evidence highlights demographic influences on disease manifestation, with age-related susceptibility patterns, etc. The two sentences above are connected by a comma rather than being two separate assertions.
Line 125. 3.2.1 Overall analysis of tIgE and sIgE by gender. Sentences that make reference to the prior writing pattern do not require bolding.
Lines 261-344: Please use consistent reference writing. The names of certain journals are abbreviated, while others are not.
Writing in English has to be improved, such as:
Line 111: Chi-squared test, typically written as the Chi-square test;
Figure 1. The inhalation allergen sIgE and the food allergen sIgE in Identification, and line 138 3.2.3 Analysis of inhalation and food allergens in different gender groups, typically written as inhaled allergens and food allergens.
Lines 118-119: Among them, 7824 patients underwent total IgE detection, and 330 patients were tested for specific IgE detection, including 90 cases with 10 food-specific IgE tests and 240 cases with 10 inhalation-specific IgE tests, typically written as 10 food allergen-specific IgE tests and 10 inhaled allergen-specific IgE tests.
Lines 173-174: In this study, the levels of total IgE and specific IgE were systematically analyzed in 7,824 patients with suspected adult allergies. It would be better if you wrote the sentence as follows: 7,824 adult patients with suspected allergies.
Lines 240-241: Further, tIgE positivity rates were highest during the summer months, suggesting that allergic diseases are more likely to occur during the summer months. It would be better to use the term the summer season than the summer months.
It is necessary to enhance the reference journal citation style, such as:
Lines 37-38, please take the citation from the original source WAO White Book, you can download it from this link https://allergypaais.org/wao-book/
Lines 39-40: Particularly concerning is the growing burden of food allergy, impacting 8% of children and 5% of adults in the United States, the United Kingdom, Canada, and Australia, respectively. According to the citation (Sicherer & Sampson, 2018), this study is from Gupta et al, used an electronic US household survey (n = 38,480) in 2009-2010 and estimated that 8% of children have food allergy, 2.4% have multiple food allergies, and about 3% experience severe reactions. The data indicating that 8% of children is derived solely from one country, specifically the US. To summarize data from multiple regions or countries, it is advisable to present it in a range.
Lines 68-69: Since this study was a cross-sectional analysis, the application for waiver of informed consent was adopted. The reason for the waiver of informed consent is not due to a cross-sectional analysis but from a retrospective study form.
Lines 77-78: Antibody levels in the serum of patients were evaluated using the Total IgE Antibody Detection Kit and Allergen-Specific IgE Antibody (sIgE) Detection Kit manufactured by HOB Biotech Group Corp., Ltd. (Suzhou, Jiangsu, China). It is advised to provide each detection kit's catalog number.
Lines 105-106: The normal reference range of tIgE can be categorized as follows: 3 to 6 years old, tIgE range was 0 to 35 IU/mL; 6 to 20 years old, tIgE range was 0 to 51 IU/mL; >20 years old, tIgE range of 0~100 IU/mL. There is an overlap at age 6; please revise the reference range.
Lines 114-116: Of the 7824 patients with suspected allergies, the number and percentage of patients tested for tIgE and sIgE varied by year as follows: 823 (10.52%) in 2018, 1157 (14.79%) in 2019, 762 (9.74%) in 2020, 1334 (17.05%) in 2021, 1639 ( 20.95%) in 2021, 1,334 (17.05%) in 2022, 1,639 (20.95%) in 2022, and 2,109 (26.95%) in 2023. Could you kindly explain why there are two numbers in each of 2021 and 2022?. Additionally, 10797 patients, not 7824, were calculated in total. Please choose which one is correct.
Lines 120-123: Allergens tested covered 20 common allergens, 10 food allergens, and 10 inhalant allergens. Food allergens included wheat, peanut, egg, soybean, milk, tomato, fish, shrimp, crab, and nuts, while inhaled allergens include dust mite, cockroach, mold, walnut pollen, elm pollen, plantain pollen, artemisia pollen, ragweed pollen, cat hair, and dog epithelium. Please add the sentences referring to Figure 2.
Lines 144-145: In addition, mold (17.07%) and dust mite (19.62%) were the main inhalation allergens in male and female patients, respectively. Please revise the main inhalation allergens into the second most common inhaled allergens.
Table 4. Please add (years) following Age.
Line 179…. and may be influenced by a variety of factors such as genetics, environment, and (?) (Lokaj-Berisha et al. 2015; Rosario et al. 2021; Tagliaferro et al. 2024). What follows is there a subsequent word or sentence?. Can you explain what is meant by genetic factors that can influence?
Lines 188-189:…while older people may be at increased risk of drug allergy due to long-term medication use (Turner et al. 2017). Since this study focuses on sensitivity to food and inhaled allergens, I don't think it's acceptable to analyze it from the standpoint of higher-risk drug allergies. It is also important to remember that total IgE levels are also influenced by various other conditions besides allergies, such as parasitic infections, immunodeficiencies, autoimmune disorders, etc.
Lines 192-199. Regarding the discussion of the results of the tIgE positive rate, which differ significantly between seasons, it is better to also compare them with the results of previous studies in other countries with 4 seasons.
This manuscript is quite good and informative, but requires various improvements as suggested by the reviewer.
This is an interesting account of specific and total IgE results in a sample of 7824 adult subjects with suspected allergies from the Liaoning province in China.
Figures and tables are well designed and reflect the results reported in the main text.
Regarding the introduction, I suggest rephrasing the fragment contained in lines 44 through 48: the first sentence may be divided into 2 separate ones for clarity, the second one (“Though mechanistic understanding remains incomplete”) is not clear and requires modification.
Regarding references, I have 2 comments:
Line 38 - The original WAO White Book on allergy should be referenced as well?
Line 40-41 – the Authors may consider referring to European data as well, in addition to the US, UK, Canada, and Australia.
Research goals have been clearly stated and defined, and they remain within the scope of the journal.
The introduction provides a proper rationale and justification for the study, identifying gaps in allergy epidemiology in that area.
Methods are described in full detail, and limitations of the methods are discussed. In this part, my main remarks concern providing the reference ranges for multiple age groups, whereas only adult subjects were considered in the study. This section could be limited to providing reference ranges for subjects 18 and older only. Moreover, in line 66, please clarify the fragment “symptoms that could not be completely ruled out”.
Please find below my remarks regarding the overall interpretation and discussion of the results.
Lines 167-169: This statement seems obvious, and I’d rather not interpret IgE in the context of pneumonia and hypertension. The reason for this interpretation is not clear, either. The obvious question is whether subjects identified as having either condition had that condition (hypertension and pneumonia) as an isolated diagnosis, or had they had some comorbidities that might affect the IgE levels? I suggest either elaborating more on the interpretation of these data or omitting this comment.
In the overall discussion and interpretation of data, there are several issues that I’d like to highlight:
1. Elevated total IgE should also be discussed and interpreted in the context of possible parasitic infestations. Is this a remarkable clinical/epidemiological problem in the Liaoning province? In the authors’ opinion, could this fact, if applicable, influence the results and their interpretation?
2. I would suggest that the authors consider adding more information about exposure to airborne allergens in the province where the study was conducted. What are the main sources of pollen, and what are their seasons of pollination? The discussion will benefit if this exposure context is added.
3. I have a little bit uneasy feeling about interpreting the results of elevated total/specific IgE in the context of the time of the year when the test was performed. Even if the seasonal exposure might have influenced the IgE levels, it should be interpreted with caution in relation to cross-sectional data. In my opinion, more definite and supported conclusions could have been drawn from the results obtained sequentially in the same patient over several time points at different times of the year. Otherwise, elevated IgE is the witness of an “atopic trait”, irrespective of its level in a given season. Could the authors comment on this possible aspect of the interpretation of their data?
4. Elevated (positive) IgE is not equal to the diagnosis of allergy. The authors briefly mention indirectly this fact (e.g., lines 228-230), but I would suggest underlining it in an even more straightforward way.
Other points of the discussion are well carried out and written, possible limitations of the study design and population selection are addressed in detail, and there’s not much to reproach.
Minor issue:
1. Terms “gender” and “sex” are used interchangeably. I suggest sticking to either of them, “sex” and “sexes” being more appropriate in this context.
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