Impaired DNase activity in patients with endocrine autoimmunity and their healthy relatives

The enzyme Deoxyribonuclease (DNase) is involved in degrading DNA during apoptosis. Impaired DNase activity has been reported to increase susceptibility to systemic lupus erythematodus. We therefore analyzed whether serum DNase activity is impaired in 112 patients with endocrine autoimmunity, their 113 relatives, and in 41 healthy controls. Patients had either pluriglandular (involvement of at least two glands, PGA, n=60) or monoglandular autoimmunity (MGA, n=70). Most frequent endocrinopathies were thyropathies (n=119), type 1 diabetes (n=44), and Addison’s disease (n=14). Serum DNase activity was quantified with a solid phase enzyme immunometric assay comprising degradation of the specific immobilised DNase substrate, formation of enzyme conjugate complexes using horseradish peroxidase conjugate solution and an enzymatic color reaction. Optical density of the probes was measured in an ELISA photometer at 450/620 nm. Pathological findings were characterized by a marked activity reduction of serum DNase (AR; cut-off: 25% AR). Compared to controls, both patients and healthy relatives showed strongly impaired DNase activities (chi-square=21.4, df=3, p<0.001). Range (median) AR in patients with PGA, MGA, healthy relatives, and controls were 2.0–57.8% (10%), 3.4–70.4% (19%), 3.6–72.5% (9%), and 4.3–16.8% (7.5%), respectively. Pathological AR in DNase was found in 23%, 30%, 10% and 0% of patients with PGA, MGA, healthy relatives, and controls, respectively. In MGA patients with Graves’ disease, Hashimoto thyroiditis, and type 1 diabetes, AR was 4.0–70.4% (median 15%), 3.4–66.9% (17%), and 8.5–57.2% (29%), respectively, whereas pathological AR was noted in 14%, 35%, and 62%, respectively. The low activity of DNase in patients with endocrine autoimmunity is either due to a lowered expression of DNASE gene or to the actin inhibition of the serum probes. Since healthy relatives also exhibit seropositive findings without clinically manifest organ failure, the determination of DNase activity may predict future autoimmune endocrine diseases.