Objectives: To investigate changes in levels of autoantibodies(Abs) against 21-hydroxylase(21OH) in APECED patients and in patients with isolated primary autoimmune adrenal insufficiency (AI) over time after manifestation of AI.
Methods: 24 patients with APECED with AI and 5 patients with isolated autoimmune AI were recruited. APECED was confirmed by finding at least two major components of the disease and/or two mutations in AIRE gene and/or high levels of antibodies against interferon-ω. APECED in patients with other forms of AI were excluded by performing genetic test and/or investigating antibodies against interferon-ω. All patients had been sampled twice. An interval time between samples was from 1 to 7 years in different patients. All blood samples were tested for autoantibodies against 21OH by ELISA.
Results: All patients had positive levels of Abs against 21OH in all their samples. But almost in all cases (24/29) levels of Abs were much higher in the first sample than in the second. Median of total percentage decrease of Ab's level was 55% [34;55] and median of percentage decrease of Ab's level per year was 18%[8;22]. Patients with longer duration of AI for the moment of first sample had lower level of Abs and more gradual percentage decrease. Only one patient had the same level of Abs in both samples with interval 5 years between them. Levels of Abs increased by 44% in one patient, who had only 1 year duration of AI at the time of sampling. Additionally two patients had unsignificant increase of levels of Abs (11% and 15%), both patients had AI during 12 years before the sampling.
Five patients had positive antibodies, but the level was near the borderline, and duration of AI in all of them was more than 15 years.
Conclusions: Reactivity against of 21OH was decreasing over time in most of patients with autoimmune AI, but in all tested patients the level of antibodies remained positive (above the cutoff) up to 19 years after manifestation of AI. Detection of Abs against 21OH could be reliable method for differential diagnosis of autoimmune AI even in patients with long-lasting AI.
The study was supported by Russian Science Foundation (grant #17-75-30035).
19 - 21 Sep 2019
European Society for Paediatric Endocrinology