Human models to understand and treat autoimmune disorders

We will use di0erent approaches to clarify what initiates an autoimmune disease and to devise better treatment:
In autoimmune diseases B- and T-cells are directed against our tissues. We will sequence variable regions of B- and T-cell receptors to identify the variable germline genes in 1000 patients with autoimmune adrenal insu0iciency and 1000 matched controls. This will allow us to understand if specific variable genes predispose for autoimmunity to develop.
Women with adrenal insu0iciency may develop autoimmune premature ovarian insu0iciency and infertility. In a small pilot study, treatment with an immune modulatory drug was given and an ovarian hyperstimulation was performed four weeks later. Almost all patients developed eggs in contrast to earlier attempts where no eggs developed with only ovarian hyper-stimulation. We have received funding and are planning for a confirmatory randomized controlled trial.
We would like to understand the molecular mechanisms when autoimmune disorders are self-limiting and cease without treatment. Postpartum thyroiditis, a thyroid inflammation that occurs after pregnancy, is such an example. In this disease patients experience severe thyroid hormone deficiency around 6 months postpartum but has recovered at 12 months. If we understand which immune mechanisms are involved during the recovery phase, we might be able to induce similar recovery phases in diseases like type 1 diabetes.