Bullous pemphigoid (BP) is a common autoimmune skin blistering disease (AIBD). It is characterized by autoantibodies targeting hemidesmosomal proteins BP180 (BPAG2) and BP230 (BPAG1) of the dermal-epidermal junction.

BP mainly affects the elderly population, with a mean age of 75 years. Therefore, we hypothesize that, additionally to inherited polymorphisms, age-associated, accumulated mutations in the nuclear and mitochondrial genome contribute to its pathogenesis.

In this study we want to investigate the role of mitochondrial genome in the pathogenesis of BP. The mitochondrial genome is approximately 16 kb in size and it mostly encodes for proteins of the oxidative phosphorylation subunits. Mutations in the mitochondrial DNA are known to affect ATP-production and ROS-release and thereby alter many cellular pathways, such as activation, proliferation, apoptosis and inflammation.

We are currently sequencing the whole mitochondrial genome of approximately 200 German BP-patients and 200 German healthy controls using next generation sequencing (NGS) technology on the MiSeq Illumina platform. We thereby hope to detect rare polymorphisms as well as potential heteroplasmy levels associated to the disease. Replication of the risk-alleles identified by NGS will be performed by genotyping an additional German and Bulgarian cohort. Eventually we aim to study the functional consequences of mitochondrial polymorphisms in a small group of patients and controls e.g. using Seahorse Assays.