Genetic diagnosis of systemic autoinflammatory diseases and underlying primary immunodeficiency

ABSTRACT

Systemic autoinflammatory diseases (SAIDs) are characterized by unprovoked inflammatory episodes such as recurrent/periodic fever, serositis, skin lesions, abdominal symptoms, arthritis/arthralgia, and central nervous system involvement. Genetic diagnosis of SAIDs has been challenging because disease manifestations overlap among themselves and with other immunological disease categories, such as infection and autoimmune diseases. However, the advent of next-generation sequencing (NGS) technologies and expanding knowledge about the innate immunity and inflammation have made the routine genetic diagnosis of SAIDs possible. Here, we review the recurrent/periodic fevers, other recently identified autoinflammatory diseases, and type I interferonopathies, and discuss the clinical usefulness of NGS targeted sequencing for SAIDs, and recent advance of understandings for this heterogeneous disease group as for underlying primary immunodeficiency.