Exploring the Link Between Allergies and Neurological Diseases: Unveiling the Hidden Connections

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

• The discussion on shared inflammatory pathways (e.g., IL-17, histamine signalling, mast cells) offers a mechanistic insight into the potential link between allergies and neurological disorders.
• Including multiple neurological conditions broadens the impact of the findings and fosters interdisciplinary discussions.
• The manuscript lacks a clear hypothesis or framework for interpreting the heterogeneous findings across studies.
• Some sections, particularly on neurodevelopmental disorders, are less detailed regarding the immunological mechanisms involved.
• Introduce a more structured hypothesis on how allergic diseases may impact neurological disorders beyond a general discussion on inflammation.
• Expand on the role of neuroinflammation in specific neurological diseases beyond general immune activation.
• Discuss alternative immune pathways that may link allergies and neurological disorders, such as the gut-brain axis.

Author Response

Comment: The discussion on shared inflammatory pathways (e.g., IL-17, histamine signalling, mast cells) offers a mechanistic insight into the potential link between allergies and neurological disorders. Including multiple neurological conditions broadens the impact of the findings and fosters interdisciplinary discussions.                                                                                                                                                            The manuscript lacks a clear hypothesis or framework for interpreting the heterogeneous findings across studies.                                                                                                                                                            Some sections, particularly on neurodevelopmental disorders, are less detailed regarding the immunological mechanisms involved. Introduce a more structured hypothesis on how allergic diseases may impact neurological disorders beyond a general discussion on inflammation. Expand on the role of neuroinflammation in specific neurological diseases beyond general immune activation.                                  Discuss alternative immune pathways that may link allergies and neurological disorders, such as the gut-brain axis.

Response:

Thank you for this insightful observation. Given the broad scope of the manuscript, the initial focus was placed primarily on epidemiological evidence, which limited the depth of pathophysiological discussion. In response to your feedback, I have revised the discussion to provide a clearer interpretation of the heterogeneous findings across studies. Additionally, I have expanded the introduction to include a paragraph addressing the potential link between allergies and neurological disorders via the gut-brain axis. Furthermore, I have enhanced the section on neurodevelopmental disorders by incorporating more detailed insights into the pathophysiological overlap with allergic diseases, extending the discussion beyond general inflammation.

Reviewer 2 Report

Comments and Suggestions for Authors

Your paper represents a careful review of the intimate immunologic mechanisms involved in common allergic diseases and certain neurological disorders. This reviewer commends the approach you followed presenting the complex data and your extensive review of the literature covering current concepts and proposals. (1) The overlap of immunopathological pathways and the intimately intertwined mechanisms are well-documented, however, and you discuss in the segment addressing MS, some studies show positive while others demonstrate negative correlations (due to genetic differences?), and frequently no significant statistical analysis in degree of clinical severity.

(2) Would you consider the presence of AD in some neurological disorders as an epiphenomenon affecting just some predisposed individuals, with no consistent epidemiologic correlation? You mentioned this situation in the 'Discussion' segment of your paper. Obviously, the pathologic targets are totally different in AD and complex neurologic diseases.  

 

Author Response

 Your paper represents a careful review of the intimate immunologic mechanisms involved in common allergic diseases and certain neurological disorders. This reviewer commends the approach you followed presenting the complex data and your extensive review of the literature covering current concepts and proposals. Question 1: The overlap of immunopathological pathways and the intimately intertwined mechanisms are well-documented, however, and you discuss in the segment addressing MS, some studies show positive while others demonstrate negative correlations (due to genetic differences?), and frequently no significant statistical analysis in degree of clinical severity.

Question2:  Would you consider the presence of AD in some neurological disorders as an epiphenomenon affecting just some predisposed individuals, with no consistent epidemiologic correlation? You mentioned this situation in the 'Discussion' segment of your paper. Obviously, the pathologic targets are totally different in AD and complex neurologic diseases.  

Response 1: 

Thank you for this insightful observation. Indeed, as highlighted in the manuscript, the immunopathological overlap between allergic and neurological diseases—such as in the case of multiple sclerosis (MS)—is complex and sometimes yields conflicting findings. These discrepancies may be attributed to several factors, including genetic heterogeneity among study populations, varying diagnostic criteria for both allergic and neurological conditions, as well as differences in study design and sample size. Additionally, the lack of standardized assessment of clinical severity and inconsistent use of statistical analyses further complicates direct comparisons across studies. I expanded this point in in the revised 'Discussion' section. 

Response 2: 

You raise an important point regarding the potential interpretation of allergic comorbidities as an epiphenomenon. While some studies do report a higher prevalence of allergic diseases in individuals with certain neurological conditions, such as MS, the epidemiologic evidence remains inconsistent. This inconsistency suggests that, in some cases, allergic conditions may indeed be an epiphenomenon occurring in genetically or immunologically predisposed individuals rather than a causative factor. I have emphasized this nuance more clearly in the revised 'Discussion' section