Autoinflammation and Autoimmunity

  • Dennis McGonagleEmail author
  • Abdulla Watad


The elucidation of the genetic basis for hereditary recurrent fever syndromes validated the role of innate immune dysregulation in diseases formerly viewed as autoimmune. Recognizing the non-autoimmune nature of tumor necrosis factor receptor-associated periodic syndrome (TRAPS), one such syndrome, and the lack of evidence for autoantibodies or B- or T-cell involvement in the context of the emergent genetics, led to the proposal of the term autoinflammation in 1999. While formally coining a new term for this type of inflammation against self, the definition was essentially stating what inflammation was not, rather than what it was. Based on the lack of an association with humoral or cellular mediated immunity and the propensity for recurrent seemingly unprovoked attacks of inflammation, fevers, elevation of inflammatory markers, without high-titer autoantibodies or antigen-specific T lymphocytes, the new designation of autoinflammatory disorders also included some conditions that would have previously been considered autoimmune, e.g. Behçet disease (BD). BD is a prime example of the two-tiered classification of inflammation against self since BD has a strong population level human leukocyte antigen (HLA)-B51 association. Given the classically defined role of major histocompatibility complex (MHC)-I molecules in peptide presentation to T cells, this incriminates adaptive immunity in BD immunopathology, which was supported by clinical therapeutics, where immunosuppressant agents like azathioprine had a proven role in disease management. The purpose of this chapter is to summarize the overlap and differences between autoinflammatory and autoimmune disorders.


Autoimmunity Autoinflammation Periodic fever Immunological diseases continuum TNF-alpha IL-1 



ANCA-associated vasculitis


Anti-citrullinated protein antibodies


Autoimmune lymphoproliferative syndrome


Adult-onset Still disease


Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy


Autoimmune thyroid disorder


Behçet disease


Cryopyrin-associated periodic syndromes


Caspase activation and recruitment domains


Chronic myelomonocytic leukaemia


Deficiency of IL-36 receptor antagonist




Disease modifying anti-rheumatic drugs


Endoplasmic reticulum aminopeptidase 1


Familial Mediterranean fever


Giant cell arteritis


Genome-wide association studies


Hyperimmunoglobulinemia D syndrome


Human leukocyte antigen


Inflammatory bowel disease






Immune dysregulation polyendocrinopathy enteropathy x-linked syndrome


Macrophage activation syndrome


Myelodysplastic syndrome (MDS)


Major histocompatibility complex


Mevalonate kinase deficiency


Reduced nicotinamide adenine dinucleotide phosphate


Nuclear factor kappa B


Nucleotide-binding oligomerization domain-like receptors


Nucleotide-binding oligomerization domain


Pyrin-associated autoinflammation with neutrophilic dermatosis


Pyogenic arthritis pyoderma gangrenosum and acne syndrome


Primary biliary cirrhosis




Psoriatic arthritis


Rheumatoid arthritis


Refractory anemia with excess blasts


Refractory cytopenia with multilineage dysplasia


Systemic juvenile idiopathic arthritis


Systemic lupus erythematosus


Single nucleotide polymorphism






Systemic sclerosis


Signal transducer and activator of transcription


Type 1 diabetes mellitus


Toll-like receptor


Tumor necrosis factor


Tumor necrosis factor receptor


Tumor necrosis factor receptor-associated periodic syndrome


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.NIHR Leeds Musculoskeletal Biomedical Research Unit, Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, Chapel Allerton HospitalUniversity of LeedsLeedsUK
  2. 2.Department of Medicine ‘B’, Zabludowicz Center for Autoimmune DiseasesSheba Medical CenterTel-HashomerIsrael
  3. 3.Sackler Faculty of MedicineTel-Aviv UniversityTel-AvivIsrael

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