An Exploratory Study of the Genetics, Pathophysiology, and Natural History of Autoinflammatory Diseases

Study Description This is an exploratory natural history protocol that will enroll patients with known or as yet undiagnosed disorders of inflammation. Blood, saliva, or buccal samples will be collected for genetic analysis, blood samples will be obtained for immunologic and other functional studies, a small number of subjects may undergo skin biopsy, leukapheresis, or bone marrow aspiration and biopsy, and some patients will be provided standard medical care follow up, with retrospective analysis of the clinical data gathered during follow up. Objectives Primary Objective: To discover the genetic basis of human disorders of inflammation. Secondary Objective: To enumerate immunologic features and genotype-phenotype associations in specific inflammatory diseases. Tertiary Objectives: To describe the clinical features of poorly characterized or newly defined disorders of inflammation, through the retrospective chart review of standard medical practice follow up and through the enrollment of selected subjects in separate, disease-specific protocols. Endpoints Primary Endpoints: The discovery of rare, high-penetrance genetic variants and common, low-penetrance genetic variants conferring susceptibility to inflammatory disease; the discovery of structural genomic variants (insertions, deletions, inversions, translocations, etc.) that cause human inflammatory disease; the discovery of common, low-penetrance germline variants that confer susceptibility to human inflammatory disease; and the discovery of somatic mutations that give rise to human inflammatory disease. Secondary Endpoint: The description of immune cell populations, inflammatory mediators, gene expression profiling, epigenetic features, and ex vivo functional assays of leukocytes from subjects with specific inflammatory diseases. Tertiary Endpoints: Given the wide range of inflammatory diseases, the endpoints will be formulated for specific conditions based on the clinical features of that condition.