Autoinflammation: Past, Present, and Future

  • Daniel L. KastnerEmail author


The concept of autoinflammation arose from the recognition of monogenic disorders with seemingly unprovoked inflammation without the high-titer autoantibodies or antigen-specific T cells seen in classic autoimmune diseases. During the first decade of the ‘autoinflammatory era’, a clear connection was established between autoinflammatory disease and the innate immune system, with targeted therapies providing a powerful affirmation of mechanistic hypotheses. Although the ‘inflammasomopathies’, which are associated with marked interleukin (IL)-1β production, were some of the earliest recognized autoinflammatory diseases, it soon became clear that autoinflammation can be caused by a variety of genetic lesions affecting a range of innate immune pathways, including nuclear factor kappa B (NF-κB) activation and type I interferon production. The advent of next-generation sequencing has resulted in the discovery of multiple new diseases, genes, and pathways, while genome-wide association studies (GWAS) have shed light on the pathogenesis of genetically complex autoinflammatory diseases, such as Behçet disease. During the next decade, the universe of autoinflammatory diseases will continue to expand, but it is likely that distinctions between clinical disease and normal variation will blur, and that treatments developed for autoinflammation will be applied to a much broader range of human illnesses.


Autoinflammation Innate immunity Inflammasome Interleukin (IL)-1β Type I interferon Next-generation sequencing Genome-wide association study (GWAS) Mosaicism Nomenclature Targeted therapy Aphthous ulcers 



Cryopyrin-associated periodic syndromes


Chronic infantile neurologic cutaneous and articular syndrome


Chronic non-bacterial osteomyelitis


Chronic recurrent multifocal osteomyelitis


Deficiency of interleukin-1 receptor antagonist


Familial Mediterranean fever


Genome-wide association studies


Hyperimmunoglobulinemia D with periodic fever syndrome




International Society for Systemic Autoinflammatory Diseases


Mevalonate kinase deficiency


Muckle-Wells syndrome


Nuclear factor kappa B


Nucleotide-binding domain, leucine-rich repeat


NLR family, pyrin domain containing 3


Neonatal-onset multisystem inflammatory disorder


Pyrin-associated autoinflammation with neutrophilic dermatosis


Pyogenic arthritis, pyoderma gangrenosum and acne


Periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis


STING-associated vasculopathy with onset in infancy


Sideroblastic anemia with immunodeficiency, fevers, and developmental delay


Stimulator of interferon genes


Tumor necrosis factor


TNF receptor-associated periodic syndrome


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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.National Human Genome Research Institute (NHGRI), National Institutes of Health (NIH)BethesdaUSA

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