Increasing Prevalence of Antinuclear Antibodies in the United States

Abstract

Objective: Growing evidence suggests increasing frequencies of autoimmunity and certain autoimmune diseases, but findings are limited by the lack of systematic data and evolving approaches and definitions. This study was undertaken to investigate whether the prevalence of antinuclear antibodies (ANA), the most common biomarker of autoimmunity, changed over a recent 25-year span in the US.

Methods: Serum ANA were measured by standard indirect immunofluorescence assays on HEp-2 cells in 14,211 participants age ≥12 years from the National Health and Nutrition Examination Survey, with approximately one-third from each of 3 time periods: 1988-1991, 1999-2004, and 2011-2012. We used logistic regression adjusted for sex, age, race/ethnicity, and survey design variables to estimate changes in ANA prevalence across the time periods.

Results: The prevalence of ANA was 11.0% (95% confidence interval [95% CI] 9.7-12.6%) in 1988-1991, 11.5% (95% CI 10.3-12.8%) in 1999-2004, and 15.9% (95% CI 14.3-17.6%) in 2011-2012 (P for trend < 0.0001), which corresponds to ~22 million, ~27 million, and ~41 million affected individuals, respectively. Among adolescents age 12-19 years, ANA prevalence increased substantially, with odds ratios (ORs) of 2.02 (95% CI 1.16-3.53) and 2.88 (95% CI 1.64-5.04) in the second and third time periods relative to the first (P for trend < 0.0001). ANA prevalence increased in both sexes (especially in men), older adults (age ≥50 years), and non-Hispanic whites. These increases in ANA prevalence were not explained by concurrent trends in weight (obesity/overweight), smoking exposure, or alcohol consumption.

Conclusion: The prevalence of ANA in the US has increased considerably in recent years. Additional studies to determine factors underlying these increases in ANA prevalence could elucidate causes of autoimmunity and enable the development of preventative measures.

Figure 1.. Prevalence of antinuclear antibodies (ANA) by time period in the U.S. population and selected subgroups.

Each circle represents a weighted estimate of ANA prevalence and the vertical bar denotes its 95% confidence interval, with blue coloring for Period 1 (1988-1991), yellow for Period 2 (1999-2004), and red for Period 3 (2011-2012). The estimates for the three periods are connected by black lines to visualize time trends. For each period, the prevalence estimate was derived from a logistic regression model for ANA positivity that adjusted for the survey design variables (strata, clusters, and sampling weights) and a single categorical covariate for the characteristic defining the subgroup. Participants with missing subgroup data (for BMI, smoking exposure, or alcohol consumption) were excluded from those analyses. The P value to assess the strength of evidence for an ANA time trend is displayed below each characteristic category and was derived from a logistic regression model that additionally adjusted for sex, age, and race/ethnicity.