Prevalence and sociodemographic correlates of antinuclear antibodies in the United States

Autoantibodies to cellular constituents are the serologic hallmarks of autoimmunity and are frequently seen in systemic autoimmune diseases, including systemic lupus erythematosus (SLE), scleroderma, and polymyositis/dermatomyositis (1). They also are detected in patients with organ-specific autoimmune diseases, such as autoimmune thyroiditis and hepatitis (1), certain infections and neoplasms (2), and in some individuals without diagnosed disease (2, 3). The most common autoantibodies are antinuclear antibodies (ANA), which are traditionally assessed by indirect immunofluorescence and include antibodies to both nuclear and cytoplasmic components (4). The cellular staining patterns and specific autoantibodies detected in those with ANA are clinically useful as they are strongly associated with particular autoimmune diseases, such as the nucleolar staining patterns that are often seen in scleroderma and anti-Sm autoantibodies that are included in SLE classification criteria (1). A variety of methods have been used to estimate ANA prevalence in selected populations, including blood donors (5, 6), hospital workers (6, 7), healthy volunteers (3, 8), or residents in small areas (9, 10), leading to a wide range of prevalence estimates (from 1.1% to 20%), which are difficult to compare. Factors associated with ANA production are largely unknown with the exception of some reports suggesting higher prevalence of ANA in females (8, 10–13) and older individuals (12, 14–16). A proportion of the ANA-positive population is thought to represent the preclinical stage of autoimmune diseases based on observations that autoantibodies are usually produced prior to clinical manifestations of disease (17). Thus, defining the prevalence and types of ANA, as well as characterizing factors associated with their production, may provide insight into the etiology of autoimmune diseases, which are thought to be increasing in frequency but are more difficult to characterize and study than ANA at the population level (18). Therefore, we evaluated serum samples from the United States (U.S.) National Health and Nutrition Examination Survey (NHANES) from 1999–2004 to estimate ANA prevalence, cellular patterns and specific autoantibody reactivities, and to identify sociodemographic and biobehavioral factors associated with their production. We specifically assessed selected systemic autoimmune disease risk factors including smoking (19) and alcohol use (20). We also evaluated C-reactive protein (21) and obesity, the former being a marker and the latter an underlying cause of chronic inflammation (22) and a growing public health concern.