Dengue Literature Review

Satoh2012 - ANA Prevalence in United States

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Satoh2012 - ANA Prevalence in United States

Full citation: Satoh M, Chan EKL, Ho LA, et al. Prevalence and sociodemographic correlates of antinuclear antibodies in the United States. Arthritis & Rheumatism 64(7), 2012: 2319–2327.

Raw file: [[raw/satoh2012.pdf]]

Summary

This study provides the first nationally representative estimates of ANA prevalence in the United States, using serum samples from 4,754 participants of NHANES 1999–2004 (ages ≥12 years). ANA were assessed by IIF on commercial HEp-2 slides at 1:80 dilution; positive was defined as staining intensity ≥3 on a 0–4 scale, calibrated against CDC reference sera and confirmed by independent dual-reader review. Specific autoantibody reactivities in ANA-positive sera were characterised by immunoprecipitation of ³⁵S-methionine-labelled K562 cell extracts.

The study found an overall ANA prevalence of 13.8%, extrapolating to ~32.3 million Americans. Clear sociodemographic correlates were established: female sex, older age, and African American race were associated with higher ANA prevalence, while overweight and obesity were paradoxically associated with lower prevalence. The data serve as a benchmark for subsequent temporal trend analyses.

Study Design

  • Type: Cross-sectional, population-representative survey
  • Sample size: 4,754 participants (from a substudy of 7,106 NHANES 1999–2004 participants selected for organochlorine assessment)
  • Setting: United States; NHANES 1999–2000, 2001–2002, 2003–2004 survey cycles
  • Population: Civilian, non-institutionalised US population, ages ≥12 years; complex multistage sampling

Key Findings

  • Overall ANA prevalence: 13.8% (95% CI 12.2–15.5%) at 1:80 dilution → ~32.3 million Americans (95% CI 28.5–36.1 million)
  • Sex: Female 17.8% vs. male 9.6% (P<0.001); age-adjusted POR 2.02 (95% CI 1.57–2.60) for females
  • Female–male POR peaked at ages 40–49 years (POR 3.57, 95% CI 2.02–6.32) and declined in older groups
  • Age: Prevalence increased non-linearly; significantly higher in 50–59 years (17.4%; POR 1.68) and 70+ years (19.2%; POR 1.88)
  • Race: Non-Hispanic Black modestly higher than White (POR 1.30, 95% CI 1.00–1.70); Mexican American similar to White
  • BMI: Overweight (POR 0.74, 95% CI 0.56–0.97) and obese (POR 0.74, 95% CI 0.59–0.94) had significantly lower ANA prevalence than normal weight — an unexpected inverse association
  • No significant associations with education, family income, alcohol, smoking (cotinine-confirmed), or C-reactive protein
  • ANA patterns in positive individuals: Nuclear 84.6%, cytoplasmic 21.8%, nucleolar 6.1%
  • Most common specific autoantibodies: Anti-Ro (3.9% of ANA+ subjects; 0.54% population), anti-Su (2.4%; 0.33% population); combined Ro/La/Su/U1RNP: 6.7% of ANA+ subjects
  • Disease-specific autoantibodies (anti-Sm, anti-topoisomerase I, anti-RNA pol I/III, anti-Jo-1) were extremely rare in this healthy population, confirming their disease specificity

Methods Used

  • Indirect Immunofluorescence ANA Test (HEp-2 substrate, Inova Diagnostics; 1:80 dilution; 0–4 scale; positivity ≥3; dual independent reader with adjudication)
  • Immunoprecipitation of ³⁵S-labelled K562 extracts (for specific autoantibodies in ANA+ sera)

Entities Mentioned

(None specific to dengue)

Concepts Addressed

Relevance & Notes

This is the primary US population-level reference for ANA prevalence at the 1:80 threshold — the same dilution used in most clinical and research IIF protocols and mandated by the 2019 EULAR/ACR SLE classification criteria (see Aringer2019 - 2019 EULAR ACR SLE Classification Criteria). The 13.8% prevalence at 1:80 in a healthy population establishes the denominator against which post-dengue ANA findings in Garcia2009 - Long-term Clinical Symptoms Post-Dengue (23.1% ANA positive) should be evaluated.

The unexpected inverse association between BMI and ANA is consistent with reports of immunosuppressive effects of adipose tissue and was replicated in Dinse2022 - Increasing ANA Prevalence in United States, though the BMI–ANA relationship appeared to shift from inverse to positive by 2011–2012.

Limitations: Cross-sectional design cannot distinguish persistent from transient ANA; NHANES excludes institutionalised individuals; not all autoantibody types were assessed by immunoprecipitation.

Questions Raised

  • Why do overweight and obese individuals have lower ANA prevalence — immunosuppression via adipokines, or reduced immune activation?
  • Are the 32 million ANA-positive Americans at elevated risk of future autoimmune disease, and what distinguishes those who progress from those who do not?
  • How do ANA correlates compare between the US population and dengue-endemic populations such as Cuba?

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