Autoinflammatory syndrome articles from across Nature Portfolio

Here, the authors describe biallelic loss-of-function variants in human SHARPIN in individuals with autoinflammation and immunodeficiency, termed sharpenia. They also successfully treat one of these individuals with TNF inhibitors.

Gain-of-function mutations in NLRP3 result in Cryopyrin-Associated Periodic Syndrome in human patients. Here authors show that although these NLRP3 variants are constitutively active, they preserve their responsiveness to external pro-inflammatory stimuli, and they interfere with the immune-metabolic inflammatory pathways in monocytes.

APLAID is a rare autoinflammatory disorder driven by mutations in PLCG2. Here the authors provide a new mouse model using the human APLAID p.Ser707Tyr mutation. The mouse recapitulates clinical features of APLAID that can be prevented by anti-G-CSF. Individuals with APLAID were also shown to have high circulating levels of G-CSF suggesting this might be a suitable target for the clinic.

Neutrophilic inflammation is a hallmark of many monogenic autoinflammatory diseases. Here the authors report a case series of three unrelated boys with perinatal-onset of neutrophilic cutaneous small vessel vasculitis and systemic inflammation, and identify de novo truncating and missense variants in the Src-family tyrosine kinase LYN.

Tumour necrosis factor (TNF) drives inflammatory responses directly by inducing inflammatory gene expression and also indirectly by inducing cell death. This article reviews the various TNF-induced cell death pathways, their mode of execution and the molecular checkpoints that control them, which is revealing new opportunities for the treatment of TNF-mediated diseases.

New findings support the use of targeted next-generation sequencing of NOD2 to reassess the diagnosis of juvenile idiopathic arthritis in patients with signs and symptoms suggestive of Blau syndrome.

Characterization of a new mouse model highlights allogeneic bone marrow transplantation and granulocyte colony-stimulating factor neutralization as potential avenues for the treatment of APLAID.

A new study provides an estimate of the prevalence of VEXAS syndrome based on the identification of pathogenic UBA1 variants in a clinical cohort.

New evidence from animal models and human studies suggests that mammalian target of rapamycin has a role in the pathophysiology of Still’s disease and macrophage activation syndrome.

Although elegant work has detailed the clinical presentation, immune response and disease outcome of multisystem inflammatory syndrome in children, many questions remain. Studies in 2022 have explored the nature of the vascular injury, the role of the SARS-CoV-2 spike protein and the association with the current variants of the virus.