Endocrine Abstracts

Autoimmune Polyendocrine Syndrome type-1 (APS-1) is a rare monogenic disease (1:100 000 frequency), caused by mutations in the autoimmune regulator (AIRE) gene, which plays a crucial role in the thymus for negative selection of self-reacting T cells. With tissue damage caused by self-reactive immune cells from early stages of life and gradually presenting with symptoms in following years, APS-1 is clinically diagnosed by presence of minimum two components of the classical triad: primary adrenal insufficiency, hypoparathyroidism, and chronic mucocutaneous candidiasis. Although two criteria of the triad are enough to make a clinical diagnosis, APS-1 can also present with multiple additional autoimmunity-associated manifestations such as malabsorption, hypothyroidism, vitiligo, or enamel hypoplasia. In this study, our goal is to provide an update on the Norwegian APS-1 cohort, include longitudinal immune profiles and relate this to course of disease, age, additional manifestations, and demographic features. We explore the longitudinal changes in distribution and quantity of immune cell subtypes in peripheral whole blood samples of APS-1 patients using the well-characterized Norwegian biobank, known as Registry of Organ-specific Autoimmune Diseases (ROAS) to obtain longitudinal patient samples. Established in 1996, ROAS is among the biggest biobanks of endocrine autoimmune diseases, containing samples spanning 25 years. We analyzed 154 samples in total, including a collection of 106 samples from 27 APS-1 patients at multiple timepoints across 25 years with 47 age and sex matched controls. The new epigenetic immune cell quantification technology allowed us to explore the longitudinal immune cell profiles in APS-1 patients, by using a panel which includes 14 cell-type specific assays. Our panel includes cell groups such as neutrophils, B-lymphocyte subgroups, Natural Killer cells, monocyte subgroups and T-lymphocyte subgroups including cytotoxic, follicular helper and regulatory cells. Overall results showed that patients having classical triad’s 3 components were diagnosed at the mean age of 7, whereas patients with less components of classical triad were diagnosed at age 11 on average. Among 27 patients, 11 had 3 components, 11 had 2 of 3 components, 5 had only 1 component of classical triad. Despite the large individual variety, the longitudinal changes in immune cell composition can be linked to clinical and genetic mutations and autoantibodies. In addition, candidiasis and hypoparathyroidism were observed more frequently than adrenal insufficiency.