Peculiarities of neuroimmune regulation in children with pathology of the autonomic nervous system under conditions of chronic exposure to airborne aluminum

Introduction. Aluminum is a common ecotoxicant, whose effect on neuroimmune regulation has not been studied sufficiently.

The purpose of the study is to assess the changes in specific indicators of neuroimmune regulation in children with autonomic nervous system disorders under conditions of chronic low-level aerogenic exposure to aluminum and in the presence of polymorphisms in candidate genes.

Materials and methods. We examined one hundred forty children exposed to emissions form a non-ferrous metallurgy enterprise (0.1 average daily MPC) including 52 children with disorders of the autonomic nervous system (ANS) (the observation group) and 88 children were considered conditionally healthy (the reference group). The expression of membrane receptors (Neuropilin-1/CD304, Notch 1) was evaluated by flow cytometry. The content of neurotropin-3, serotonin, and specific IgG for aluminum was determined by enzyme immunoassay (ELISA). Evaluation of polymorphism of SOD2 (rs2758330) and HTR2A (rs7997012) genes by using the polymerase chain reaction method (PCR).

Results. Children chronically exposed to low-dose airborne aluminum (0.1 average daily MPC) and had ANS disorders were found to have elevated blood aluminum levels (0.011±0.001 mg/dm³). These levels were authentically 1.7 times higher than reference levels (0.0065±0.0035 mg/dm³) and 2.75 times higher (p=0.0001) than aluminum levels identified in their conditionally healthy peers (0.004±0.001 mg/dm³). The children from the observation group were also shown to have inhibited NRP1 and Notch 1 expression compared to the reference group (2.0–2.3 times lower; p≤0.05), as well as hyperproduction of neurotropin-3 and IgG specific to aluminum (1.38–1.48 times higher; p≤0.05). We found a strong correlation between bioexposure to aluminum and hyperproduction of neurotropin-3 (R²=0.86; p≤0.05) and IgG to aluminum (R²=0.52; p≤0.05). As association was established between expression of the SOD2 C14510A gene (allele A and genotype AA) and the HTR2A rs7997012 gene (allele G and genotype GG) and the risk (RR=1.47–1.56) of autonomic nervous system disorders upon exposure to aluminum.

Limitations. The study was accomplished on a small sample of children (52 cases) with pathology of the autonomic nervous system.

Conclusion. Thus, chronic aerogenic exposure to aluminum causes an imbalance of neuroimmune regulation in children, which is confirmed by the studied markers, promising for further research.

Compliance with ethical standards. The study was conducted in conformity with the Declaration of Helsinki, the World Medical Association “Ethical Principles for Medical Research Involving Human Participants” and the National Standard of the Russian Federation GOST-R 52379–2005 Good Clinical Practice (ICH E6 GCP) (Meeting Report No. 6 dated April 03, 2024). All participants and their legal representatives gave informed voluntary written consent to participate in the study.

Contributions:
Alikina I.N. – data collection and analysis, writing and editing the text;
Dolgikh О.V. – study concept and design, writing and editing the text, approval of the final version of the manuscript;
Shirinkina А.S. – data collection and analysis, writing and editing the text.
All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version

Conflict of interest. The authors declare no conflict of interest.

Funding. The study had no sponsorship.

Received: July 18, 2025 / Accepted: , 2025 / Published: October 20, 2025

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