title: Biomarkers of methylmercury exposure immunotoxicity among fish consumers in Amazonian Brazil.
abstract: BACKGROUND
  Mercury (Hg) is a ubiquitous environmental contaminant with neurodevelopmental and immune system effects. An informative biomarker of Hg-induced immunotoxicity could aid studies on the potential contribution to immune-related health effects.
  
  
  OBJECTIVE
  Our objectives were to test the hypothesis that methylmercury (MeHg) exposures affect levels of serum biomarkers and to examine interactions between Hg and selenium (Se) in terms of these responses.
  
  
  METHODS
  This cross-sectional epidemiological study assessed adults living along the Tapajós River, a system long affected by MeHg. We measured antinuclear (ANA) and antinucleolar (ANoA) autoantibody levels and eight cytokines in serum samples (n = 232). Total Hg (including MeHg) and Se were measured in blood, plasma, hair, and urine.
  
  
  RESULTS
  The median (range) total Hg concentrations were 14.1 μg/g (1.1-62.4), 53.5 μg/L (4.3-288.9), 8.8 μg/L (0.2-40), and 3.0 μg/L (0.2-16.1) for hair, blood, plasma, and urine, respectively. Elevated titers of ANA (but not ANoA) were positively associated with MeHg exposure (log-transformed, for blood and plasma), unadjusted [odds ratio (OR) = 2.6; 95% confidence interval (CI): 1.1, 6.2] and adjusted for sex and age (OR = 2.9; 95% CI: 1.1, 7.5). Proinflammatory [interleukin (IL)-6 and interferon (IFN)-γ], anti-inflammatory (IL-4), and IL-17 cytokine levels were increased with MeHg exposure; however, in the subset of the population with elevated ANA, proinflammatory IL-1β, IL-6, IFN-γ, and tumor necrosis factor (TNF)-α and anti-inflammatory (IL-4) cytokine levels were decreased with MeHg exposure. Although Se status was associated with MeHg level (correlation coefficient = 0.86; 95% CI: 0.29, 1.43), Se status was not associated with any changes in ANA and did not modify associations between Hg and ANA titers.
  
  
  CONCLUSIONS
  MeHg exposure was associated with an increased ANA and changes in serum cytokine profile. Moreover, alterations in serum cytokine profiles differed based on ANA response, suggesting a specific phenotype of MeHg susceptibility. Further research on the potential health implications of these observed immunological changes is warranted.
authors.affiliation: Department of Pathology, Microbiology, and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina 29209, USA. jnyland@uscmed.sc.edu
authors.forename: Jennifer F
authors.initials: JF
authors.lastname: Nyland
authors.forename: Myriam
authors.initials: M
authors.lastname: Fillion
authors.forename: Fernando
authors.initials: F
authors.lastname: Barbosa
authors.forename: Devon L
authors.initials: DL
authors.lastname: Shirley
authors.forename: Chiameka
authors.initials: C
authors.lastname: Chine
authors.forename: Melanie
authors.initials: M
authors.lastname: Lemire
authors.forename: Donna
authors.initials: D
authors.lastname: Mergler
authors.forename: Ellen K
authors.initials: EK
authors.lastname: Silbergeld
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D001938:Brazil; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000097:blood; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000097:blood / Q000378:metabolism* / Q000652:urine; D005399:Fishes / Q000378:metabolism*; D006801:Humans; D000922:Immunotoxins / Q000097:blood / Q000378:metabolism* / Q000652:urine; D008767:Methylmercury Compounds / Q000097:blood / Q000378:metabolism* / Q000652:urine; D016017:Odds Ratio; D012643:Selenium / Q000378:metabolism*
chemical_list: D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D015415:Biomarkers; D016207:Cytokines; D004785:Environmental Pollutants; D000922:Immunotoxins; D008767:Methylmercury Compounds; D012643:Selenium