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Autoinflammation: Past, Present, and Future

  • Daniel L. KastnerEmail author
Chapter

Abstract

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.

Keywords

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

Abbreviations

CAPS

Cryopyrin-associated periodic syndromes

CINCA

Chronic infantile neurologic cutaneous and articular syndrome

CNO

Chronic non-bacterial osteomyelitis

CRMO

Chronic recurrent multifocal osteomyelitis

DIRA

Deficiency of interleukin-1 receptor antagonist

FMF

Familial Mediterranean fever

GWAS

Genome-wide association studies

HIDS

Hyperimmunoglobulinemia D with periodic fever syndrome

IL

Interleukin

ISSAID

International Society for Systemic Autoinflammatory Diseases

MKD

Mevalonate kinase deficiency

MWS

Muckle-Wells syndrome

NF-κB

Nuclear factor kappa B

NLR

Nucleotide-binding domain, leucine-rich repeat

NLRP3

NLR family, pyrin domain containing 3

NOMID

Neonatal-onset multisystem inflammatory disorder

PAAND

Pyrin-associated autoinflammation with neutrophilic dermatosis

PAPA

Pyogenic arthritis, pyoderma gangrenosum and acne

PFAPA

Periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis

SAVI

STING-associated vasculopathy with onset in infancy

SIFD 

Sideroblastic anemia with immunodeficiency, fevers, and developmental delay

STING

Stimulator of interferon genes

TNF

Tumor necrosis factor

TRAPS

TNF receptor-associated periodic syndrome

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Copyright information

© 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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