Ex vivo exposure to polybrominated diphenyl ether (PBDE) selectively affects the immune response in autistic children

Marjannie Eloi Akintunde; Yan-Ping Lin; Paula Krakowiak; Isaac N Pessah; Irva Hertz-Picciotto; Birgit Puschner; Paul Ashwood; Judy Van de Water

doi:10.1016/j.bbih.2023.100697

Ex vivo exposure to polybrominated diphenyl ether (PBDE) selectively affects the immune response in autistic children

Brain Behav Immun Health. 2023 Oct 28:34:100697. doi: 10.1016/j.bbih.2023.100697. eCollection 2023 Dec.

Authors

Marjannie Eloi Akintunde^{1

2}, Yan-Ping Lin^{3

4

2}, Paula Krakowiak^{4

5}, Isaac N Pessah^{3

4

2}, Irva Hertz-Picciotto^{4

5}, Birgit Puschner^{3

2}, Paul Ashwood^{4

2

6}, Judy Van de Water^{1

4

2}

Affiliations

¹ School of Medicine, Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, United States.
² NIEHS Center for Children's Environmental Health, University of California, Davis, United States.
³ Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, United States.
⁴ The MIND Institute, University of California, Davis, United States.
⁵ School of Public Health Sciences, University of California, Davis, United States.
⁶ School of Medicine, Department of Microbiology and Immunology, University of California, Davis, United States.

Abstract

Children on the autism spectrum have been shown to have immune dysregulation that often correlates with behavioral deficits. The role of the post-natal environment in this dysregulation is an area of active investigation. We examined the association between plasma levels of polybrominated diphenyl ether (PBDE) and immune cell function in age-matched autistic children and non-autistic controls. Plasma from children on the autism spectrum (n = 38) and typically developing controls (TD; n = 60) were analyzed for 14 major PBDE congeners. Cytokine/chemokine production was measured in peripheral blood mononuclear cell (PBMC) supernatants with and without ex vivo BDE-49 exposure. Total plasma concentration (∑_PBDE14) and individual congener levels were also correlated with T cell function. ∑_PBDE14 did not differ between diagnostic groups but correlated with reduced immune function in children on the autism spectrum. In autistic children, IL-2 and IFN-γ production was reduced in association with several individual BDE congeners, especially BDE-49 (p = 0.001). Furthermore, when PBMCs were exposed ex vivo to BDE-49, cells from autistic children produced elevated levels of IL-6, TNF-α, IL-1β, MIP-1α and MCP-1 (p < 0.05). Therefore, despite similar plasma levels of PBDE, these data suggest that PBMC function was differentially impacted in the context of several PBDE congeners in autistic children relative to TD children where increased body burden of PBDE significantly correlated with a suppressed immune response in autistic children but not TD controls. Further, acute ex vivo exposure of PBMCs to BDE-49 stimulates an elevated cytokine response in AU cases versus a depressed response in TD controls. These data suggest that exposure to the toxicant BDE-49 differentially impacts immune cell function in autistic children relative to TD children providing evidence for an underlying association between susceptibility to PBDE exposure and immune anomalies in children on the autism spectrum.

Keywords: Autism; Autism spectrum; Autistic; Cytokines; Flame retardants; Immunology; Polybrominated diphenyl ethers.

Abstract

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