Subtype-resolved characterisation of human alopecia areata

Alopecia areata (AA) is a common, chronic, immune-mediated disease characterized by the acute onset of non-scarring hair loss. Regardless of the extent of the hair loss and the fact that it is an autoimmune reaction, this immune response always remains limited to the hair. Therefore, it is commonly regarded as a harmless, purely cosmetic condition. Nevertheless, many studies consistently showed that the disease can have considerable effects on a patients quality of life leading to increased rates of depression and unemployment. While the number of available therapies increased considerably in the last years, studies show that in most patients with extensive disease a durable cure cannot be achieved. Four main variants are observed in humans: patch-type AA, ophiasis-pattern AA, AA totalis (loss of all scalp hair), and AA universalis (also loss of body hair). A large number of studies comprehensively showed that a specific type of T cell, an important player of the immune system, is the cause for the immune mediated hair follicle destruction in AA. Nevertheless, different clinical phenotypes are not understood and the cause of the disease is unclear. In this project, we aim to increase our immunological understanding of AA in order to arrive at more efficient therapies. We hypothesize that AA is wider spread than clinically expected but is initially controlled by regulatory immune mechanisms. These exist to prevent excessive immune responses during infections and also protect our body from autoimmune diseases. We believe that differences in the initial immune response may cause the different clinical phenotypes we observe. These differences could maybe explain why people react differently to the same therapies. An increased understanding of these factors may subsequently help us to select more efficient therapies for each individual patient and even lead to new treatment strategies altogether. The project will be conducted at the Department of Dermatology at the Medical University of Vienna. The principal investigator, Johannes Griss, is a board certified dermatologist leading a bioinformatics research group. Over the last ten years we have developed multiple algorithms to analyze omics including scRNA-seq data and integrate this data on the pathway level. We will collaborate with Stephan Wagners group who have profound experience in multiplex immunofluorescence analyses. We are therefore able to conduct this project in a highly specialized research environment with profound experience in clinical immunologic research.