P02-006 - A novel PSTPIP1 mutation in PAPA syndrome

Introduction Pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome is an autosomal dominant autoinflammatory disease caused by mutations in the proline-serinethreonine phosphatase-interacting protein 1, PSTPIP1. The produced protein is a cytoskeleton-associated adaptor protein that modulates T-cell activation, cytoskeletal organization and IL-1b release. The only two mutations described so far, A230T and E250Q, have been found in patients and families, and are thought to disrupt the binding of PSTPIP1 with PTPPEST, a regulatory phosphatase, and increase its avidity for pyrin in the cytosol, thereby dysregulating IL-1b production. PAPA syndrome typically presents with recurrent sterile, erosive arthritis in childhood, resulting in significant joint destruction. By puberty, joint problems tend to subside and cutaneous symptoms increase including pathergy, frequently with abscesses at the sites of injections, severe cystic acne, and recurrent non-healing sterile ulcers, often diagnosed as pyoderma gangrenosum.