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Diagnostics 2015, 5(2), 219-253; doi:10.3390/diagnostics5020219

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

1
Klinikum Traunstein, Cuno-Niggl-Str. 3, Traunstein 83278, Germany
2
Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Sigmund-Freud Str. 15, Bonn 53127, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Ludmilla A. Morozova-Roche
Received: 10 April 2015 / Revised: 1 June 2015 / Accepted: 5 June 2015 / Published: 16 June 2015
(This article belongs to the Special Issue Biomarkers in Blood)
View Full-Text   |   Download PDF [942 KB, uploaded 16 June 2015]   |  

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. View Full-Text
Keywords: HMBG1; RAGE; circulation; biomarkers; prognosis; therapy response; tumor; autoimmune disease; DAMP HMBG1; RAGE; circulation; biomarkers; prognosis; therapy response; tumor; autoimmune disease; DAMP
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Pilzweger, C.; Holdenrieder, S. Circulating HMGB1 and RAGE as Clinical Biomarkers in Malignant and Autoimmune Diseases. Diagnostics 2015, 5, 219-253.

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