title: Air pollution and children: neural and tight junction antibodies and combustion metals, the role of barrier breakdown and brain immunity in neurodegeneration.
abstract: Millions of children are exposed to concentrations of air pollutants, including fine particulate matter (PM2.5), above safety standards. In the Mexico City Metropolitan Area (MCMA) megacity, children show an early brain imbalance in oxidative stress, inflammation, innate and adaptive immune response-associated genes, and blood-brain barrier breakdown. We investigated serum and cerebrospinal fluid (CSF) antibodies to neural and tight junction proteins and environmental pollutants in 139 children ages 11.91 ± 4.2 y with high versus low air pollution exposures. We also measured metals in serum and CSF. MCMA children showed significantly higher serum actin IgG, occludin/zonulin 1 IgA, IgG, myelin oligodendrocyte glycoprotein IgG and IgM (p < 0.01), myelin basic protein IgA and IgG, S-100 IgG and IgM, and cerebellar IgG (p < 0.001). Serum IgG antibodies to formaldehyde, benzene, and bisphenol A, and concentrations of Ni and Cd were significantly higher in exposed children (p < 0.001). CSF MBP antibodies and nickel concentrations were higher in MCMA children (p = 0.03). Air pollution exposure damages epithelial and endothelial barriers and is a robust trigger of tight junction and neural antibodies. Cryptic 'self' tight junction antigens can trigger an autoimmune response potentially contributing to the neuroinflammatory and Alzheimer and Parkinson's pathology hallmarks present in megacity children. The major factor determining the impact of neural antibodies is the integrity of the blood-brain barrier. Defining the air pollution linkage of the brain/immune system interactions and damage to physical and immunological barriers with short and long term neural detrimental effects to children's brains ought to be of pressing importance for public health.
authors.affiliation: The Center for Structural and Functional Neurosciences, The University of Montana, Missoula, MT, USA.
authors.forename: Lilian
authors.initials: L
authors.lastname: Calderón-Garcidueñas
authors.affiliation: Immunosciences Laboratory, Los Angeles, CA, USA.
authors.forename: Aristo
authors.initials: A
authors.lastname: Vojdani
authors.affiliation: Clinical and Environmental Laboratories, Micro Trace Minerals (MTM), Hersbruck, Germany/Trace Minerals International (TMI), Boulder, CO, USA.
authors.forename: Eleonore
authors.initials: E
authors.lastname: Blaurock-Busch
authors.affiliation: Clinical and Environmental Laboratories, Micro Trace Minerals (MTM), Hersbruck, Germany/Trace Minerals International (TMI), Boulder, CO, USA.
authors.forename: Yvette
authors.initials: Y
authors.lastname: Busch
authors.affiliation: Clinical and Environmental Laboratories, Micro Trace Minerals (MTM), Hersbruck, Germany/Trace Minerals International (TMI), Boulder, CO, USA.
authors.forename: Albrecht
authors.initials: A
authors.lastname: Friedle
authors.affiliation: Hospital Central Militar, Secretaria de la Defensa Nacional, Mexico City, Mexico.
authors.forename: Maricela
authors.initials: M
authors.lastname: Franco-Lira
authors.affiliation: Mathematics Department, Boise State University, Boise, Idaho, USA.
authors.forename: Partha
authors.initials: P
authors.lastname: Sarathi-Mukherjee
authors.affiliation: Universidad Autónoma de Piedras Negras, UAPN, Piedras Negras, Coahuila, México.
authors.forename: Xavier
authors.initials: X
authors.lastname: Martínez-Aguirre
authors.affiliation: NICER Lab, Department of Neuroscience, Carleton University, Ottawa, Ontario, Canada.
authors.forename: Su-Bin
authors.initials: SB
authors.lastname: Park
authors.affiliation: Centro de Ciencias de la Atmósfera, Universidad Nacional Autónoma de México, Mexico City, Mexico.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Torres-Jardón
authors.affiliation: NICER Lab, Department of Neuroscience, Carleton University, Ottawa, Ontario, Canada.
authors.forename: Amedeo
authors.initials: A
authors.lastname: D'Angiulli
mesh_terms: D000293:Adolescent; D000393:Air Pollutants / Q000633:toxicity*; D000397:Air Pollution / Q000009:adverse effects*; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D002648:Child; D004781:Environmental Exposure; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism*; D008297:Male; D008800:Mexico; D009410:Nerve Degeneration / Q000209:etiology* / Q000276:immunology / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D019108:Tight Junctions / Q000276:immunology / Q000378:metabolism
chemical_list: D000393:Air Pollutants; D007136:Immunoglobulins
keywords: Air pollution; Alzheimer's disease; children; innate and adaptive immunity; neurodegeneration; neuroinflammation; particulate matter; tight junction and neural reactive autoantibodies