Rubella immunity and serum perfluoroalkyl substances: Sex and analytic strategy

Abstract

BackgroundPerfluoroalkyl substances (PFASs) have been associated with decreased immunity to childhood tetanus and diphtheria immunizations. If these vaccinations are vulnerable to influence from PFASs, questions arise about associations with other common inoculations.ObjectiveTo examine whether serum PFASs were associated with reduced immunity to rubella immunization, and whether interactions with sex or ethnicity warranted analytic stratification. Usually, toxicology analyses are calculated controlling for race and sex. However, sex differences in immune function have been reported and a reduction of immunity to rubella in women could pose risks such miscarriage.MethodsWe analyzed a nationally representative sample of individuals ≥ 12 years from the National Health and Nutrition Examination Survey (NHANES) for years 1999–2000 and 2003–2004 for whom PFAS measures were available. Our analytic strategy was to start with separate analyses for youth and adults controlling for several covariates including ethnicity and sex, as well as the interaction of these terms with PFASs. If there was a main effect of PFASs and an interaction term, we would stratify analyses of effect size. The outcome variable was Rubella IgG titers by quartile of perfluoroalkyl substances.ResultsAfter exclusion for missing data, the analyzed sample contained 581 adult women, 621 adult men, and 1012 youth. There was no significant effect of PFASs on immunity in youths but a significant effect of both PFOA and PFOS in adults, as well as a significant interaction of PFOA x sex and a borderline significant interaction of PFOS x sex. When effect size analyses were stratified by sex, a significant association between rubella titres and PFOA was found in men but not women and PFOS was not significant in either sex.ConclusionsThese results support our earlier studies showing sex specific responses to PFASs and indicate the importance of thinking carefully about analytic strategies in population based toxicology research.

Perfluoroalkyl substances exposure and immunity, allergic response, infection, and asthma in children: review of epidemiologic studies

“…The studies in this review focused on pediatric vaccination including TDaP (Tetanus, Diphtheria, Pertussis) and MMR. As described previously, elevated PFAS were associated with reduced humoral immune response to routine childhood immunizations, including lower levels of tetanus and anti-diphtheria antibodies ( Abraham et al., 2020 ; Grandjean et al., 2012 ; Mogensen, Grandjean, Heilmann, et al., 2015 ) and for mumps ( Stein et al., 2016 ) and rubella ( Granum et al., 2013 ; Pilkerton et al., 2018 ; Stein et al., 2016 ) antibody titers.…”

“…Among seropositive individuals, increased blood serum levels of PFOS were associated with a 5.9% decrease in mumps antibody titers and a 13.3% decrease in rubella antibody titers (Stein et al, 2016). A recent analysis of the National Health Nutrition Examination Survey (NHANES) results for children aged 12-18 years showed no association between serum rubella titers and PFOA or PFOS levels (Pilkerton, Hobbs, Lilly, & Knox, 2018). These findings vary by study and vaccine component, limiting the ability to draw overarching conclusions.…”

Serum Perfluoroalkyl Substances, Vaccine Responses, and Morbidity in a Cohort of Guinea-Bissau Children

“…Recent studies have analyzed data on adolescents in the cross-sectional 1999–2000 and 2003–2004 NHANES. Although one found no association between serum PFAS concentrations and rubella antibodies among 1,012 12- to 18-y-olds ( Pilkerton et al. 2018 ), the other found PFAS to be associated with reduced concentrations of mumps and rubella, although not measles, antibodies among 1,191 12- to 19-y-olds ( Stein et al.…”

“…The Norwegian study also showed a trend toward reduced measles antibody concentrations with elevated concentrations of PFHxS, PFOS, PFOA, and PFNA, but the associations were not significant, possibly due to the small sample size (n = 50) (Granum et al 2013). Recent studies have analyzed data on adolescents in the cross-sectional 1999cross-sectional -2000cross-sectional and 2003cross-sectional -2004 Although one found no association between serum PFAS concentrations and rubella antibodies among 1,012 12-to 18-y-olds (Pilkerton et al 2018), the other found PFAS to be associated with reduced concentrations of mumps and rubella, although not measles, antibodies among 1,191 12-to 19-y-olds Adjusted for weight (to nearest 10 g) and age (days) at inclusion, sex, maternal education (none/any/unknown), and breastfeeding without solids (inclusion: yes/no, 9-month visit: duration in days).…”

Pollution, Inflammation, and Vaccines: A Complex Crosstalk

“…Moreover, a recent report has shown that high levels of PFOA are associated with low rubella vaccine antibodies in adult men [ 122 ]. PFOA exposure also causes a lower influenza vaccine response in adult people [ 123 ].…”