Endocrine Medicine

Two new high impact publications from the group

Our long term collaboration with the research group of Jakub Abramson at Weizmanns institute in Israel har resulted in two new publications in high ranked journals

Degree of Aire function is correlated with severity of disease
Bergithe Oftedal

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1. Journal of clinical investigation: A partial form of AIRE deficiency underlies a mild form of autoimmune polyendocrine syndrome type 1 (Bergithe E. Oftedal)

Aire is a gene involved in maturation of immune cells in the thymus, and people with non-functioning Aire gets a autoimmune polyendocrine syndrome (APS-1) with several autoimmune manifestations. We have identifed a new splice version of Aire in patients that leads to a shorter protein that still functions, but not to the same degree as the whole length protein. The splice version gives a milder form of disease. We created mice with this splice-version, and they had lower degree of autoimmune infiltration in organs than a Aire-knockout, as well as reduced transcriptonal effects in the thymus. This paper illustrate an association between the degree of AIRE activity and the severity of autoimmune disease, with implications for more common autoimmune diseases associated with AIRE variants, such as primary adrenal insufficiency, pernicious anemia, type 1 diabetes, and rheumatoid arthritis.

1. Nature: Autoimmune amelogenesis imperfecta in patients with APS-1 and coeliac disease (Anette Wolff)

One of the most common hallmarks of patients with APS-1 is defects in enamel development or enamel hypoplasia. The mechanism behind this has not yet been understood, but in this paper we demonstrate autoantibodies in patients towards enamel proteins. Aire knockout mice showed defective enamel production and autoantibodies to enamel proteins. We then investigated whether this could be a pathologic mechanism in other diseases as well. Up to 50% of children with celiac disease develop enamle pathologies similar to APS-1, and we detected autoantibodes to several enamel proteins in celiac patients compared with controls. These proteins share epitopes with intestinal  (TGM2, LAMB3 and common food antigens (K-casein), so celiac disease and intake of milk can result in enamel injuries in patients, especially in childre.