New genes, pathways and therapeutic targets in autoinflammatory diseases

Studies in 2023 have described eight new monogenic autoinflammatory diseases and their accompanying disease-causing mutations, uncovering clinical phenotypes, pathogenic mechanisms and therapeutic targets. Researchers have identified autoinflammatory pathways linked to mitochondrial dysfunction or overactivation of SRC family kinases. Characterization of a new autoinflammatory disease, loss of IL-1 receptor sensitivity to its antagonist (LIRSA), highlights the role of IL-1 in sterile bone inflammation and led to the development of an IL-1 inhibitor4.Newly discovered mutations cause an ARF-dependent type interferonopathy, the characterization of which provides pathogenic insight and supports a link between type I interferon signalling, mitochondrial dysfunction and neurological impairment7.Three family carrying autosomal dominant mutations in present with disabling pansclerotic morphea partially responsive to ruxolitinib, demonstrating the potential of JAK inhibition in this previously untreatable disorder8.Gain-of-function mutation in , which encodes a SRC tyrosine kinase, is associated with an autoinflammatory disease responsive to TNF inhibition and the SRC kinase inhibitor dasatinib, adding to an emerging group of diseases known as kinasopathies9.