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S100 Proteins in Autoinflammation

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Textbook of Autoinflammation

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.

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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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Authors and Affiliations

  1. Department of Pediatric Hematology-Oncology, University of Duisburg-Essen, Essen, Germany

    Dirk Holzinger

  2. Department of Pediatric Rheumatology and Immunology, University Children’s Hospital Muenster, Muenster, Germany

    Christoph Kessel & Dirk Foell

Authors
  1. Dirk Holzinger
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  2. Christoph Kessel
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  3. Dirk Foell
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Correspondence to Dirk Foell .

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Editors and Affiliations

  1. Pediatric Rheumatology Unit, Shaare Zedek Medical Center and Hebrew University, Jerusalem, Israel

    Philip J. Hashkes

  2. Department Paediatrics, Division of Rheumatology, The Hospital for Sick Children and University of Toronto, Toronto, ON, Canada

    Ronald M. Laxer

  3. Department of Internal Medicine, Radboudumc Expertisecenter for Immunodeficiency and Autoinflammation, Radboud University Medical Center, Nijmegen, The Netherlands

    Anna Simon

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Holzinger, D., Kessel, C., Foell, D. (2019). S100 Proteins in Autoinflammation. In: Hashkes, P., Laxer, R., Simon, A. (eds) Textbook of Autoinflammation. Springer, Cham. https://doi.org/10.1007/978-3-319-98605-0_9

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  • DOI: https://doi.org/10.1007/978-3-319-98605-0_9

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