Warning: Autoimmunity on the Rise in the U.S.

The prevalence of autoimmunity, as suggested by the presence of antinuclear antibodies (ANA), has been rising in the United States, a large cross-sectional study found.
Data from the National Health and Nutrition Examination Survey (NHANES) showed an overall ANA prevalence of 11% (95% CI 9.7-12.6) for 1988-1991; 11.5% (95% CI 10.3-12.8) for 1999-2004; and 15.9% (95% CI 14.3-17.6) for 2011-2012 (P<0.0001 for trend), according to Frederick W. Miller, MD, PhD, of the National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina, and colleagues.

As they reported online in Arthritis & Rheumatology, those numbers corresponded with totals of 22 million, 27 million, and 41 million affected individuals across the 25-year time frame.
The presence of ANA is the most common biomarker for autoimmunity, occurring in patients with many conditions such as systemic lupus erythematosus and rheumatoid arthritis. The antibodies also are sometimes seen in the general population, particularly among women and the elderly and after exposures to chemicals and infections, Miller and co-authors noted.
“Growing evidence suggests that autoantibodies precede the onset of symptomatic autoimmune disease by many years; thus, ANA may be an intermediate marker on the pathway to disease or may signal increased susceptibility to autoimmune diseases through related causal pathways,” the researchers explained.
Earlier studies had suggested that the rates of autoimmune disease were increasing, but it’s been unclear whether this represented better detection or a true increase, so Miller and colleagues analyzed the prevalence of ANA positivity in the nationally representative NHANES database for 1988-2012.

The analysis included 14,211 individuals ages 12 and older from the three time periods who completed questionnaires on demographics and health factors and also provided blood samples. Indirect immunofluorescence was used to detect ANA.
Of the included individuals, 13.9% were positive for ANA. At all three time intervals, the likelihood of ANA positivity was two to three times higher for women than men, with odds ratios of 2.53 (95% CI 1.90-3.36) for 1988-1991, 2.97 (95% CI 2.30-3.84) for 1999-2004, and 1.94 (95% CI 1.57-2.40) for 2011-2012.
Antibody positivity also was more common among individuals age 50 and older compared with adolescents, with odds ratios of 3.63 (95% CI 2.02-6.55), 1.80 (95% CI 1.23-2.63), and 1.71 (95% CI 1.21-2.42) for the three time periods, respectively.
The odds of ANA positivity also were higher for blacks and Mexican-Americans in the earliest time period, but ethnic/racial differences declined in the two later time periods.
In a time-trend analysis, the researchers reported “strong evidence” for an increasing prevalence of ANA positivity in the two later time periods compared with the first (reference) period, with overall prevalence odds ratios of 1.02 (95% CI 0.85-1.24) for 1999-2004 and 1.47 (95% CI 1.22-1.78, P<0.0001 vs reference) by 2011-2012.

The greatest rise in prevalence was between the second and third time periods, and by 2011-2012 the prevalence odds ratios were significantly increased in these subgroups (vs the baseline period):

• Men, OR 1.73 (95% CI 1.31-2.30, P<0.0001)

• Women, OR 1.35 (95% CI 1.08-1.69, P=0.008)

• Adolescents, OR 2.88 (95% CI 1.64-5.04, P<0.0001)

• Older adults, OR 1.51 (95% CI 1.17-1.95, P=0.001)

• Non-Hispanic whites, OR 1.66 (95% CI 1.30-2.12, P<0.0001)

• Overweight individuals, OR 1.88 (95% CI 1.33-2.65, P=0.0001)

• Second-hand smoke exposure, OR 1.65 (95% CI 1.29-2.12, P=0.0002)

• Moderate/heavy alcohol consumption, OR 2.41 (95% CI 1.55-3.75, P<0.0001)

“Our novel and robust findings suggest that ANA prevalence increased substantially in the U.S. over the 25-year time frame examined,” the investigators wrote.
They described the “dramatic” increase in ANA positivity in adolescence as “particularly concerning if ANA are harbingers of increased susceptibility to future autoimmune diseases.”
A study limitation, the team said, was the cross-sectional design.
The researchers added: “Additional studies to complement our exploratory investigation, particularly of the aforementioned sociodemographic groups, should be the focus of future research to determine the driving forces underlying these ANA increases and to inform the development of possible preventative measures.”

Last Updated April 08, 2020

Disclosures

The authors reported no financial conflicts of interest.

Primary Source

Arthritis & Rheumatology

Source Reference: Dinse G, et al “Increasing prevalence of antinuclear antibodies in the United States” Arthritis Rheum 2020; DOI: 10.1002/art.41214.

https://www.medpagetoday.com/rheumatology/generalrheumatology/85842