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S100 Proteins in Autoinflammation

  • Dirk Holzinger
  • Christoph Kessel
  • Dirk FoellEmail author
Chapter

Abstract

Among the putative markers for autoinflammatory diseases, studies on phagocyte-derived S100 proteins (S100A8/A9, S100A12: calgranulins) are the most advanced to date. Translational studies have suggested an important role for these danger-associated molecular pattern (DAMP) molecules as robust inflammation biomarkers.

S100A8/A9 and S100A12 can be released from monocytes and granulocytes via so-called alternative secretory pathways. When extracellular, they can operate as proinflammatory endogenous toll like receptor (TLR)4-ligands. Tissue and serum concentrations of S100 proteins correlate with disease activity, both during local and systemic inflammatory processes. In autoinflammatory diseases such as familial Mediterranean fever (FMF), PSTPIP1-associated inflammatory diseases (PAID) or systemic juvenile idiopathic arthritis (SJIA), dysregulation of alternative secretory pathways may be involved in the pathogenesis. Resulting calgranulin-hypersecretion can then aggravate disease in a feed-forward loop together with IL-1β.

Analysis of S100A8/A9 and A12 concentrations in patients’ specimens is a valuable supportive tool in the difficult diagnosis of SJIA and FMF and in investigating fever of unknown origin. Furthermore, calgranulins can be used to monitor disease activity to subclinical level, as their serum concentrations decrease with successful treatment. Their expression and function in disease may provide a better understanding of autoinflammatory mechanisms and calgranulins may pose novel therapeutic targets for future treatments.

Keywords

S100 proteins Autoinflammation Danger associated molecular patterns Biomarker Fever of unknown origin Diagnosis Monitoring TLR agonist Calgranulins 

Abbreviations

AIDAI

Autoinflammatory disease activity index

AOSD

Adult-onset still disease

CAPS

Cryopyrin associated periodic syndromes

DAMP

Danger-associated molecular pattern

FMF

Familial Mediterranean fever

FUO

Fever of unknown origin

IL

Interleukin

LPS

Lipopolysaccharide

MMP

Matrix metalloproteinase

MRP

Myeloid-related protein

MWS

Muckle-Wells syndrome

NET

Neutrophil extracellular trap

NOMID

Neonatal-onset multisystem inflammatory disease

PAID

PSTPIP1-associated inflammatory diseases

PAMI

PSTPIP1-associated myeloid-related proteinemia inflammatory syndrome

PAMP

Pathogen associated molecular pattern

PAPA

Pyogenic sterile arthritis, pyoderma gangrenosum, and acne syndrome

PBMC

Peripheral blood mononuclear cell

PFAPA

Periodic fever, aphthous stomatitis, pharyngitis, adenitis syndrome

RAGE

Receptor for advanced glycation end products

sJIA

Systemic juvenile idiopathic arthritis

TLR

Toll like receptor

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Pediatric Hematology-OncologyUniversity of Duisburg-EssenEssenGermany
  2. 2.Department of Pediatric Rheumatology and ImmunologyUniversity Children’s Hospital MuensterMuensterGermany

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