Main objective

Primary objective: To bring novel diagnostics and therapeutics for autoimmune
diseases to clinical use through studies of monogenic autoimmune diseases

Organ-specific autoimmune diseases have a prevalence of about 10 percent in the Norwegian population and comprise a diverse group of debilitating disorders where the immune system attacks and disrupts cellular functions leading to loss of tissue integrity and physiology. Many patients have two or more of these diseases and they tend to aggregate in families. The mechanisms causing disease (pathogenesis) is thought to be the result of complex interactions between the environment and multiple genes (50-100), although combined they cannot explain the extreme heritability of organ-specific autoimmune diseases.

Many patients have two or more of these diseases and there is a strong hereditable component. The pathogenesis is thought to be the result of complex interactions between genetic and environmental factors, but the detailed pathogenic mechanisms operational in the individual patient are largely unknown. Furthermore, we do not understand why a person develops a certain organ-specific disease or diseases and others not. Thus, appropriate personalized diagnostic and predictive biomarkers and aetiology-based treatment strategies are lacking leading to increased morbidity, heightened mortality and reduced quality of life.

Previous research has been hindered by lack of well-defined cases and cohorts, appropriate model systems and inaccessibility of affected organs. However, we are now in the unique position to overcome these hurdles. Building on our world-leading expertise and a translational medical approach we aim to bring forward novel personalized diagnostic and therapeutic modalities to the clinic in concordance with UiB and HUS’ strategic documents.

In order to reach these ambitious goals we will rely heavily on monogenic autoimmune diseases as models to understand common autoimmune diseases.

Autoimmune diseases caused by one gene (monogenic) represent “experiments of nature” with proven potential to identify key regulatory points and pathways in the immune system and how these are altered in more common diseases. We recently found that monogenic autoimmune diseases are much more common than previously thought, and we are now hunting for other monogenic diseases using large well-characterized cohorts of patients with autoimmune adrenal insufficiency (AAD) and experimental mouse models. AAD is remarkable among the autoimmune diseases in its homogeneity at the clinical and immunological level. We therefore believe that novel genetic approaches and functional characterization will give us increased insight into common organ-specific autoimmune diseases enabling earlier diagnosis and personalized treatment and follow-up.

h the use of novel technologies. These include methods enabling studies of single cells obtained from affected organs of patients which will be instrumental to understand human autoimmune disease. Thus, integrating our biobanks and registries of carefully selected samples, tissues and phenotypes from patients with data from informative and relevant gene-modified mouse models should provide a sound basis for KGJCA to bring novel diagnostics and therapeutics to the clinic.