Sex differences in the association between antinuclear antibody positivity with diabetes and multimorbidity in older adults: Results from the Baltimore Longitudinal Study of Aging.

Antinuclear antibodies (ANA), a marker of self-reactivity to DNA and other nuclear antigens, are present in several autoimmune diseases and have been observed in healthy persons in the absence of autoimmune disease. ANA prevalence is higher in women and older adults, but the health implications of ANA in middle- to older-aged adults are unknown. Immune system differences by sex may further result in sex-specific susceptibility to morbidity. In a cross-sectional analysis of data from the Baltimore Longitudinal Study of Aging, we examined the sex-specific relationship between age and ANA as well as the associations (odds ratios and 95% confidence intervals) between ANA and type-2 diabetes and multimorbidity (2 or more chronic diseases), stratified by sex and controlling for age and race. ANA was measured in a 1:160 dilution of sera by immunofluorescence using HEp-2 cells (seropositive = 3 or 4). Overall ANA seroprevalence was 12% (15.1% in women, 8.8% in men). We observed a non-linear relationship between age and ANA that varied by sex (interaction p-value < 0.05), with a clear sex differences in younger participants (ages 48-59), which converged in the oldest (age 80+). ANA positive women had higher odds of type 2 diabetes (OR: 2.06, 95% confidence interval: 1.04, 4.07) and multimorbidity (OR: 2.47, 95% confidence interval 1.11, 5.50) than women who were ANA negative. No statistically significant associations were observed in men. Insight into differences in age-related ANA positivity and ANA associations with chronic diseases by sex is important for understanding the impact of immune dysregulation in aging individuals.