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Autoinflammation and Autoimmunity

  • Dennis McGonagleEmail author
  • Abdulla Watad
Chapter

Abstract

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.

Keywords

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

Abbreviations

AAV

ANCA-associated vasculitis

ACPA

Anti-citrullinated protein antibodies

ALPS

Autoimmune lymphoproliferative syndrome

AOSD

Adult-onset Still disease

APECED

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy

ATD

Autoimmune thyroid disorder

BD

Behçet disease

CAPS

Cryopyrin-associated periodic syndromes

CARD

Caspase activation and recruitment domains

CMML

Chronic myelomonocytic leukaemia

DITRA

Deficiency of IL-36 receptor antagonist

DM

Dermatomyositis

DMARD

Disease modifying anti-rheumatic drugs

ERAP-1

Endoplasmic reticulum aminopeptidase 1

FMF

Familial Mediterranean fever

GCA

Giant cell arteritis

GWAS

Genome-wide association studies

HIDS

Hyperimmunoglobulinemia D syndrome

HLA

Human leukocyte antigen

IBD

Inflammatory bowel disease

IFN

Interferon

IL

Interleukin

IPEX

Immune dysregulation polyendocrinopathy enteropathy x-linked syndrome

MAS

Macrophage activation syndrome

MDS

Myelodysplastic syndrome (MDS)

MHC

Major histocompatibility complex

MKD

Mevalonate kinase deficiency

NADPH

Reduced nicotinamide adenine dinucleotide phosphate

NF-ĸB

Nuclear factor kappa B

NLR

Nucleotide-binding oligomerization domain-like receptors

NOD

Nucleotide-binding oligomerization domain

PAAND

Pyrin-associated autoinflammation with neutrophilic dermatosis

PAPA

Pyogenic arthritis pyoderma gangrenosum and acne syndrome

PBS

Primary biliary cirrhosis

PM

Polymyositis

PsA

Psoriatic arthritis

RA

Rheumatoid arthritis

RAEB

Refractory anemia with excess blasts

RCMD

Refractory cytopenia with multilineage dysplasia

SJIA

Systemic juvenile idiopathic arthritis

SLE

Systemic lupus erythematosus

SNP

Single nucleotide polymorphism

SNS

Self/non-self

SpA

Spondyloarthropathies

SSc

Systemic sclerosis

STAT

Signal transducer and activator of transcription

T1DM

Type 1 diabetes mellitus

TLR

Toll-like receptor

TNF

Tumor necrosis factor

TNFR

Tumor necrosis factor receptor

TRAPS

Tumor necrosis factor receptor-associated periodic syndrome

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© 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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