title: Old Dogs, New Tricks: Monogenic Autoinflammatory Disease Unleashed.
abstract: Autoinflammatory diseases are inborn disorders of the innate immune system characterized by episodes of systemic inflammation that are mediated largely by myeloid cells. The field of autoinflammatory diseases has been established since 1999, following the identification of the first genes underlying periodic fever syndromes. This review focuses on developments that have transformed the field in the last two years. We discuss three newly described monogenic autoinflammatory diseases [deficiency of adenosine deaminase 2 (DADA2), a subtype of macrophage activation syndrome (MAS), and stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI)], discuss the possibilities of somatic mosaicism and digenic inheritance, and give an update on new concepts in pathways involved in familial Mediterranean fever (FMF). Finally, the new monogenic autoinflammatory disease haploinsufficiency of A20 (HA20) underscores the placement of monogenic diseases in the firmament of common autoinflammatory phenotypes. The advances in the last two years have shed light on the pathophysiology of several autoinflammatory diseases and have elucidated new pathways that play a role in innate immunity.
authors.affiliation: Metabolic, Cardiovascular, and Inflammatory Disease Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892; email: kastnerd@mail.nih.gov.
authors.forename: Monique
authors.initials: M
authors.lastname: Stoffels
authors.affiliation: Metabolic, Cardiovascular, and Inflammatory Disease Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892; email: kastnerd@mail.nih.gov.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Kastner
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics* / Q000276:immunology; D010505:Familial Mediterranean Fever / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D057895:Haploinsufficiency / Q000235:genetics / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007249:Inflammation / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3 / Q000235:genetics*; D000099197:STING Protein
chemical_list: D000243:Adenosine Deaminase; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; C532857:STING1 protein, human; D000099197:STING Protein; C076529:TNFAIP3 protein, human; C408373:ADA2 protein, human
keywords: DADA2; HA20; PRAAS; SAVI; Schnitzler syndrome; macrophage activation syndrome