Li2019 - ANA Epidemiology in Chinese Healthy Population

Full citation: Li X, Liu X, Cui J, et al. Epidemiological survey of antinuclear antibodies in healthy population and analysis of clinical characteristics of positive population. Journal of Clinical Laboratory Analysis 2019;00:e22965.

Raw file: [[raw/li2019.pdf]]

Summary

A retrospective epidemiological survey of ANA positivity among 25,110 individuals attending routine health checkups at Baoding No.1 Central Hospital, Hebei, China, from January 2015 to June 2018. Ages ranged from 4 months to 93 years. The study both estimates ANA prevalence across dilution thresholds in a large East Asian health-checkup population and characterises the clinical correlates of specific autoantibodies (particularly AMA-M2 and anti-SSA) in high-titer ANA-positive individuals.

The study found prevalence broadly consistent with US and international data at comparable dilution levels. A key secondary finding was that 37.4% of AMA-M2-positive individuals met PBC diagnostic criteria, underscoring the clinical importance of identifying high-titer ANA in asymptomatic health-checkup populations.

Study Design

  • Type: Retrospective cross-sectional epidemiological survey
  • Sample size: 25,110 health-checkup attendees (12,640 males, 12,470 females)
  • Setting: Baoding No.1 Central Hospital, Baoding, Hebei, China; January 2015 – June 2018
  • Population: Mixed community population including workers, peasants, cadres, students, kindergarteners; ages 4 months – 93 years. Individuals with chronic active hepatitis, tuberculosis, or chronic infection were excluded

Key Findings

  • ANA titer >1:100: 14.01% overall (male 9.04%, female 19.05%; P<0.01; χ²=522.06)
  • ANA titer >1:320: 5.93% overall (male 3.21%, female 8.68%; P<0.01; χ²=337.05)
  • Female:male ratio ~2.08× at >1:100 threshold; ~2.67× at >1:320 threshold
  • Among 1,489 individuals with ANA >1:320 who underwent specific antibody testing by LIA: 44.29% had ≥1 specific antibody; top 3 were anti-Ro-52 (n=212), AMA-M2 (n=189), anti-SSA (n=144)
  • AMA-M2-positive group (n=189): 46.0% had abnormal blood routine, 42.3% abnormal liver function, 48.2% abdominal discomfort; 37.4% met PBC diagnostic criteria (elevated ALP); fatigue in 24.3%, pruritus in 6.9%
  • Anti-SSA-positive group (n=144): 50.0% abnormal blood routine, 58.3% elevated ESR, 41.0% abnormal liver function; elevated IgG (13.2%), decreased C3/C4 (16.7%), elevated rheumatoid factor (20.1%)

Methods Used

  • Indirect Immunofluorescence ANA Test (HEp-2 cells; Euroimmun AG; manufacturer’s protocol; serial dilutions reported at >1:100 and >1:320 thresholds)
  • Line Immunoassay (LIA; Euroimmun AG; EUROBlotMaster) for 15 specific autoantibodies in ANA+ >1:320 samples, at 1:100 serum dilution

Entities Mentioned

(None specific to dengue)

Concepts Addressed

  • Antinuclear Antibodies (central topic: East Asian healthy population prevalence; specific antibody distribution)
  • Autoimmunity in Dengue (provides Chinese population baseline at a dilution approximating clinical ANA thresholds)

Relevance & Notes

The 14.01% prevalence at >1:100 in this Chinese health-checkup cohort is strikingly similar to the 13.8% found in the US NHANES population at 1:80 (see Satoh2012 - ANA Prevalence in United States), supporting the universality of ~14% ANA positivity near the 1:80–1:100 threshold range. The lower threshold (>1:320) prevalence of 5.93% is consistent with Tan1997 - ANA Range in Healthy Individuals’s 5.0% at 1:160 in a European/international multicentre cohort, though the Li2019 cutoff is higher.

Important methodological caveat: this is a health-checkup cohort, not a random population sample — it may overrepresent symptomatic individuals and working-age adults, potentially inflating the true population prevalence. The paper’s primary focus is on clinical characterisation of ANA-positive individuals rather than on providing a definitive population prevalence estimate.

The study also demonstrates that a substantial minority of individuals with high-titer ANA in health-checkup settings have subclinical autoimmune disease (particularly PBC and Sjögren’s-spectrum disease), suggesting that ANA detected at lower clinical dilutions may also reflect pre-clinical autoimmune pathology.

Limitations: Health-checkup cohort (not population-representative); no age-stratified breakdown reported; dilution thresholds (>1:100, >1:320) differ from the international standard 1:80 and 1:160 used in Tan1997 and Satoh2012, limiting direct comparison.

Questions Raised

  • How do ANA prevalence and specific antibody distributions compare between Chinese and dengue-endemic South/Southeast Asian populations?
  • What proportion of the 5.93% >1:320 population in health-checkup settings would progress to clinically diagnosed autoimmune disease on long-term follow-up?