Acute Kawasaki disease is associated with reverse regulation of soluble receptor for advance glycation end products and its proinflammatory ligand S100A12.

Abstract

OBJECTIVE:

Receptor for advanced glycation end products (RAGE) serves as a pattern recognition receptor for several endogenous ligands that are potent inducers of inflammation. By activating endothelial cells and leukocytes, RAGE augments recruitment of leukocytes to sites of inflammation, which is a key process, especially in vasculitis. Soluble RAGE (sRAGE) acts as a naturally occurring inhibitor of RAGE by neutralizing proinflammatory ligands, e.g., S100A12. This neutrophil-derived protein has been reported to be associated with Kawasaki disease (KD) and to provoke proinflammatory responses. The aim of this study was to investigate circulating sRAGE in an acute inflammatory disorder and to compare these data directly with concentrations of the proinflammatory RAGE ligand S100A12.

METHODS:

Serum concentrations of sRAGE and S100A12 were analyzed by specific enzyme-linked immunosorbent assays in 50 children with KD, and additionally in 39 patients with juvenile idiopathic arthritis (JIA). In 28 of the patients with KD, levels were analyzed longitudinally over the course of the disease.

RESULTS:

Patients with KD and those with systemic-onset JIA had decreased levels of sRAGE during active disease, especially those patients with KD who were more severely affected and not responding to treatment. In addition, the level of sRAGE correlated negatively with the level of proinflammatory S100A12. After intravenous immunoglobulin (IVIG) therapy in patients with KD, the S100A12:sRAGE ratio was significantly different between responders and nonresponders.

CONCLUSION:

Inverse regulation of both sRAGE and its proinflammatory ligand S100A12 seems to be a relevant molecular mechanism promoting systemic inflammation. Calculating the S100A12:sRAGE ratio might help to detect patients with KD who are at risk of being unresponsive to IVIG therapy.

• Authors: Helmut Wittkowski, Keiichi Hirono, Fukiko Ichida, Thomas Vogl, Fei Ye, Xing Yanlin, Kazuyoshi Saito, Keiichiro Uese, Toshio Miyawaki, Dorothee Viemann, Johannes Roth, Dirk Foell
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 56 Issue 12 Pg. 4174-81 (Dec 2007) ISSN: 0004-3591 [Print] United States
• PMID: 18050248 (Publication Type: Journal Article)

Chemical References

• Biomarkers
• Immunoglobulins, Intravenous
• Immunologic Factors
• Receptor for Advanced Glycation End Products
• Receptors, Immunologic
• S100 Proteins
• S100A12 Protein
• S100A12 protein, human

Topics

• Arthritis, Juvenile (blood)
• Biomarkers (blood)
• Case-Control Studies
• Child
• Child, Preschool
• Female
• Follow-Up Studies
• Humans
• Immunoglobulins, Intravenous (therapeutic use)
• Immunologic Factors (therapeutic use)
• Infant
• Longitudinal Studies
• Male
• Mucocutaneous Lymph Node Syndrome (blood, drug therapy)
• Receptor for Advanced Glycation End Products
• Receptors, Immunologic (blood)
• S100 Proteins (blood)
• S100A12 Protein