LAUSR

Abstract In the last 20 years, new primary immunodeficiencies (PIDs) affecting the immunity mediated by interferon (IFN)-γ, IFN-α/β-λ, Toll and interleukin-1 receptor (TIR) domain nuclear factor (NF)-κB, Toll-like receptor (TLR)-3 pathway, and interleukin (IL)-17 have been identified. Some of these genetic defects are “conventional” PIDs, associated with a broad range of infections, but others provide a molecular explanation for severe pediatric infectious diseases previously thought to be idiopathic. These “nonconventional” PIDs may be associated with severe and/or recurrent infections caused by a single family of microorganisms, a situation strongly contrasting with that for “conventional” PIDs. Standard immunological explorations are generally normal in these patients, whether they are susceptible to one infection or to many infectious agents. Despite the lack of a clear immunological abnormality, infections in these patients are typically severe and often fatal. All these disorders were initially thought to be rare, but they have since been diagnosed in about 800 patients around the world.