Monogenic autoinflammatory diseases or systemic autoinflammatory diseases (SAIDs) are disorders of the innate immune system characterized by pathogenic variants in a single gene. To date over 40 genes have been linked to these conditions. Symptoms of these conditions can include recurrent fevers, rashes, arthritis/arthralgia, myalgia, GI inflammation neurological features, elevated acute phase reactants, immunodeficiency, bone marrow failure and more. Symptoms vary broadly both within and between conditions and can range from severe and to mild and early to late onset. Early and accurate diagnosis of these conditions is imperative for clinical management, often including treatment with biologic agents. Next generation sequencing (NGS) is increasingly being used in the evaluation of patients with suspected autoinflammatory diseases, leading to a growing number of variants being identified in both known and candidate genes. Causative genes are found in various segments of the innate immune system including inflammasome-mediated, NF-κB-mediated or interferon-mediated inflammatory signaling pathways, cytokine receptors, the actin cytoskeleton, proteasome complexes, various enzymes and more.

The goal of the Monogenic Autoinflammatory Diseases GCEP will be to evaluate the validity of genes implicated in the autoinflammatory diseases. The initial gene list was drafted to include genes included on the International Union of Immunological Societies (IUIS) Autoinflammatory List (Table 7) (PMID32048120) and genes that are included on commercially available NGS panels. We expect that this list will grow as the field advances.