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Circulating HMGB1 and RAGE as Clinical Biomarkers in Malignant and Autoimmune Diseases.

Authors
  • Pilzweger, Christin1
  • Holdenrieder, Stefan2
  • 1 Klinikum Traunstein, Cuno-Niggl-Str. 3, Traunstein 83278, Germany. [email protected] , (Germany)
  • 2 Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Sigmund-Freud Str. 15, Bonn 53127, Germany. [email protected] , (Germany)
Type
Published Article
Journal
Diagnostics
Publisher
MDPI AG
Publication Date
Jun 16, 2015
Volume
5
Issue
2
Pages
219–253
Identifiers
DOI: 10.3390/diagnostics5020219
PMID: 26854151
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

High molecular group box 1 (HMGB1) is a highly conserved member of the HMG-box-family; abundantly expressed in almost all human cells and released in apoptosis; necrosis or by activated immune cells. Once in the extracellular space, HMGB1 can act as a danger associated molecular pattern (DAMP), thus stimulating or inhibiting certain functions of the immune system; depending on the "combinatorial cocktail" of the surrounding milieu. HMGB1 exerts its various functions through binding to a multitude of membrane-bound receptors such as TLR-2; -4 and -9; IL-1 and RAGE (receptor for advanced glycation end products); partly complex-bound with intracellular fragments like nucleosomes. Soluble RAGE in the extracellular space, however, acts as a decoy receptor by binding to HMGB1 and inhibiting its effects. This review aims to outline today's knowledge of structure, intra- and extracellular functions including mechanisms of release and finally the clinical relevance of HMGB1 and RAGE as clinical biomarkers in therapy monitoring, prediction and prognosis of malignant and autoimmune disease.

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