Association between Vitamin D Deficiency and Antinuclear Antibodies in Middle-Aged and Older U.S. Adults

Meier, Helen C.S.; Sandler, Dale P.; Simonsick, Eleanor M.; Parks, Christine G.

doi:10.1158/1055-9965.epi-16-0339

Cited by 9 publications

(6 citation statements)

References 24 publications

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“…Vitamin D levels may also be influenced by UV exposure ( 23 ). Lower vitamin D levels were previously found to be associated with ANA in middle aged and older adults in the NHANES (2001-2004) ( 24 ), but in the current study sample of younger adults and adolescents, higher vitamin D appeared positively associated with ANA (age-adjusted OR 1.43 for ≥75 versus 50-75 nmol/L). We saw no evidence of confounding by vitamin D levels; though in the summer sample the association of log 10 BP-3 with ANA appeared to be inverse, this may be due to chance or confounding or interactions with other unmeasured factors.…”

Section: Discussioncontrasting

confidence: 79%

Benzophenone-3 and antinuclear antibodies in U.S. adolescents and adults ages 12-39 years

et al. 2022

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BackgroundBetween 1988 and 2012, prevalence of antinuclear antibodies (ANA) increased in the U.S., especially in adolescents and non-Hispanic Whites. Female predominance of ANA suggests a role for hormonal factors, including xenobiotic exposures that may disrupt endocrine signaling. Benzophenone-3 (BP-3) is one such chemical with increasing exposure through sunscreen use. We investigated whether urinary BP-3 levels were related to ANA in adolescents and young adults.MethodsIn a sample of 1,785 individuals ages 12-39 years in the National Health and Nutrition Examination Survey (NHANES; 2003-4, 2011-12), we examined cross-sectional associations of ANA (N=192; 3+ or 4+ at the 1:80 dilution, measured by HEp-2 immunofluorescence) with urinary BP-3, and other phenols bisphenol-A, triclosan, and parabens. Adjusted prevalence odds ratios (POR) were calculated in season-stratified models [winter (November-April) and summer (May-October)], given differences in sunscreen use and BP-3 concentrations.ResultsBP-3 concentrations (detected in >98.5% of individuals) did not differ by ANA positivity in the summer (geometric mean, GM 30.6 ng/ml ANA-positive vs. 35.3 ANA-negative; GM ratio 1.15), but in winter were higher among ANA-positives (50.2 vs. 20.1 ANA-negative; GM ratio 2.50). ANA was associated with log10BP-3 in winter (POR 1.57; 95%CI 1.07-2.30 per unit increase) but not summer (0.94; 0.61, 1.44; interaction p=0.09). Triclosan, parabens, and bisphenol-A levels were unrelated to ANA overall or by season (ORs 0.64 to 1.33).ConclusionsThe association of urinary BP-3 with ANA in the winter may reflect different exposure patterns or unmeasured confounders. Findings warrant replication in prospective studies and including past and year-round exposures.

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Section: Discussioncontrasting

confidence: 79%

Benzophenone-3 and antinuclear antibodies in U.S. adolescents and adults ages 12-39 years

et al. 2022

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“…In sensitivity analyses, we additionally controlled for country of birth, smoking status and household size, as these factors may influence exposure to hygiene hypothesis indicators, but the addition of these potential confounders did not meaningfully change effect estimates. Our previous work has shown that vitamin D deficiency was associated with ANA positivity in older US adults (aged 50+) (34). In the current study, however, no statistically significant differences in vitamin D levels by ANA status were observed, therefore it was not considered as a confounder.…”

Section: Discussioncontrasting

confidence: 72%

Hygiene Hypothesis Indicators and Prevalence of Antinuclear Antibodies in US Adolescents

et al. 2022

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Autoimmunity prevalence, as measured by antinuclear antibodies (ANA), is increasing in U.S. adolescents. Improved hygiene and cleaner environments in childhood may reduce exposure to infections and other immune challenges, resulting in improper immune responses to later-life exposures. We examined associations of hygiene hypothesis indicators, including asthma, allergies, and antibodies to infectious agents, with ANA prevalence, measured by HEp-2 immunofluorescence, in adolescents (aged 12-19 years) over a 25-year time span in the National Health and Nutrition Examination Survey (NHANES) (N=2,709), adjusting for age, sex, race/ethnicity, body mass index, education and survey cycle, overall and within individual time periods, using logistic regression. Prevalence of ANA in adolescents increased from 5.0% in 1988-1991 to 12.8% in 2011-2012. ANA were positively associated with diagnosis of asthma in early childhood (OR: 2.07, CI: 1.09–3.99) and the effect estimate for current hay fever was elevated but not statistically significant (OR: 1.55, CI: 0.85–2.84). Fewer than 2% of those with ANA in 1988-1991 had been diagnosed with asthma, compared with 18% in 1999-2000, and 27% in 2003-2004 and 2011-2012. ANA trended negatively with Helicobacter pylori antibodies (OR: 0.49, CI: 0.24–0.99). ANA may be useful as an additional indicator of inadequate immune education in adolescence, a critical period of growth and development.

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“…Similar to what has been previously described in ANA-positive healthy individuals [6,7] we hypothesized that an abnormal status of immunomodulatory vitamin D could play a role in anti-BP180-NC16A reactivity in healthy persons. In fact, hypovitaminosis D has been reported to be more common in AIBD patients than in the general population [8,9] but nothing is known about vitamin D and BP autoantibodies in healthy populations.…”

Section: Introductionmentioning

confidence: 56%

Bullous pemphigoid anti-BP180-NC16A autoantibody reactivity in healthy individuals is associated with marked hypovitaminosis D and Th2-like cytokine predominance

Tukaj

Bieber

Prüßmann

et al. 2022

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Autoimmune bullous disease autoantibodies, particularly including bullous pemphigoid (BP)-related anti-BP180-NC16A IgG, have been reported in a small subset of healthy individuals, but information about associated factors is lacking. We hypothesized that an abnormal status of immunomodulatory vitamin D could play a role in anti-BP180-NC16A autoantibody reactivity in healthy persons. In addition, we aimed to evaluate the cytokine profile associated with these autoantibodies. Plasma samples from 34 anti-BP180-NC16A IgG-reactive and 85 anti-BP180-NC16A IgG-negative healthy blood donors were tested for levels of 25-hydroxyvitamin D [25(OH)D] and a wide range of cytokines (IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-17A, IL-17F, IL-21, IL-22, IFN-γ, and TNF-α). We observed that anti-BP180-NC16A IgG-reactive healthy subjects had significantly lower plasma 25(OH)D levels and about a two-fold higher rate of vitamin D deficiency (< 20 ng/ml) compared to anti-BP180-NC16A IgG-negative healthy persons. In addition, anti-BP180-NC16A IgG-positive samples were characterized by significantly higher levels of IL-2, IL-5, IL-9, IL-10, and IL-13. Our results indicate that healthy individuals with BP autoantibody reactivity share similarities with BP patients regarding the vitamin D status and cytokine profile (i.e., marked hypovitaminosis D and Th2 predominance), which may have pathophysiologic and treatment (i.e., early/prophylactic vitamin D supplementation) implications.

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Association between Vitamin D Deficiency and Antinuclear Antibodies in Middle-Aged and Older U.S. Adults

Cited by 9 publications

References 24 publications

Benzophenone-3 and antinuclear antibodies in U.S. adolescents and adults ages 12-39 years

Benzophenone-3 and antinuclear antibodies in U.S. adolescents and adults ages 12-39 years

Hygiene Hypothesis Indicators and Prevalence of Antinuclear Antibodies in US Adolescents

Bullous pemphigoid anti-BP180-NC16A autoantibody reactivity in healthy individuals is associated with marked hypovitaminosis D and Th2-like cytokine predominance

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