Clinical Conditions Associated With a High Antinuclear Antibody Titer in Individuals Without Autoimmune Disease

Antinuclear antibodies (ANAs) are present at high titers in 2% of the general population, but their clinical significance in individuals without an autoimmune (AI) disease is not known. We tested the hypothesis that the presence of a high ANA titer in non-AI conditions is associated with disease.

We conducted a retrospective case-control study in the Vanderbilt University Medical Center's de-identified electronic medical record system. Individuals without AI disease who had an ANA test were classified into three groups: high titer (HT; ANA ≥ 1:640), low titer (LT; ANA ≤ 1:80), and negative (NG) ANA results. The prevalence of diagnoses recorded within 90 days of the ANA test were compared among groups in a phenome-wide association study adjusting for age at ANA testing, sex, median body mass index (BMI), and reported race. A P value <5 × 10^-5 was considered significant.

A total of 28,781 individuals qualified for the study: 3.1% in the HT, 12.3% in the LT, and 84.6% in the NG groups. BMI was similar among groups (P value = 0.345), but individuals in the HT group were older (P = 3.9 × 10^-73). A high ANA titer increased risk of 46 and 67 clinical diagnoses when comparing the HT group with the LT and the NG groups, respectively. The most significant associations in both comparisons included liver disorders and complications and risk factors for liver disease.

A high ANA titer in the absence of an AI disease was associated with increased risk of liver disorders and related risk factors and complications.