Research in practice: Immune checkpoint inhibitor related autoimmune bullous dermatosis

Immune checkpoint receptors and ligands such as cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed death-1 (PD-1) and ligand-1 (PD-L1) are widely expressed on immune and non-immune cells and fine tune the activation level of immune cells, thus, enabling, preventing, or terminating immune responses. Blockade of CTLA-4, PD-1 or PD-L1 by checkpoint inhibitors (CIs), unleashing immune responses, has become a mainstay in the treatment of diverse types of cancer. The induction of autoinflammatory, yet unspecific tissue damage in diverse organs is called an immune related adverse event (irAE), a class side-effect of CIs and may require the discontinuation of immunotherapy. Among frequent skin rashes, CIs targeting the PD-L1/PD-1 axis can elicit the IgG autoantibody- and granulocyte-driven bullous pemphigoid (BP) in about 0.3% to 0.6% of treated patients. Pathogenesis of BP requires a complex cellular inflammatory response after anti-BP180 autoantibody binding to the dermal epidermal junction. The prevalence of autoantibodies against BP180 in healthy blood donors of approximately 0.52% equals the prevalence of irBP among treated cancer patients, underlining the potential relevance of the PD-1 mediated regulation of tissue inflammation for spontaneous BP. If skin rashes appear during CI therapy, biopsies should be taken and examined by histopathological and direct immunofluorescence microscopy.