Large molecular size EDTA-resistant complexes containing S100A12, ERAC, in serum during inflammatory conditions

Abstract The pro-inflammatory, leukocyte-derived S100A12 protein occurs as calcium-dependent oligomers in serum, while EDTA plasma from the majority of healthy individuals contains only monomers. Addition of 5 mM EDTA to serum leads to a rapid dissociation of the oligomers in most samples. However, using gel permeation chromatography, we have found that sera from some patients and seemingly healthy individuals contain molecular complexes in the 400–1000 kDa range reacting with anti-S100A12 even in the presence of EDTA; for these we introduce the name ERAC (EDTA Resistant S100A12 Complexes). Based upon monoclonal antibodies and the lateral flow principle, we have developed a quantitative rapid ERAC test giving results within 10 minutes. The highest prevalence of ERAC positivity was found in sera from patients with concomitant rheumatoid arthritis and coronary heart disease. The structure of ERAC is not yet known. Further studies are needed to analyse the mechanism behind the appearance of ERAC and the possible association with inflammatory-related diseases.

[1]  D. Atar,et al.  Tumor Necrosis Factor-&agr; Antagonists Improve Aortic Stiffness in Patients With Inflammatory Arthropathies: A Controlled Study , 2010, Hypertension.

[2]  J. Goyette,et al.  Pleiotropic Roles of S100A12 in Coronary Atherosclerotic Plaque Formation and Rupture1 , 2009, The Journal of Immunology.

[3]  A. Larsen.  Inflammatory biomarkers with focus on Calprotectin (S100A8/S100A9) and S100A12 (EN-RAGE) : method development and application in acute radiation proctitis and rheumatoid arthritis patients , 2007 .

[4]  T. Wentzel‐Larsen,et al.  Quantification of S100A12 (EN‐RAGE) in Blood Varies with Sampling Method, Calcium and Heparin , 2007, Scandinavian journal of immunology.

[5]  T. Lyberg,et al.  Increase in plasma calprotectin during long‐distance running , 2005, Scandinavian journal of clinical and laboratory investigation.

[6]  D. Foell,et al.  Monitoring neutrophil activation in juvenile rheumatoid arthritis by S100A12 serum concentrations. , 2004, Arthritis and rheumatism.

[7]  O Fitzgerald,et al.  Expression of the pro-inflammatory protein S100A12 (EN-RAGE) in rheumatoid and psoriatic arthritis. , 2003, Rheumatology.

[8]  D. Foell,et al.  Neutrophil derived human S100A12 (EN-RAGE) is strongly expressed during chronic active inflammatory bowel disease , 2003, Gut.

[9]  T. Vogl,et al.  Phagocyte-specific S100 proteins: a novel group of proinflammatory molecules. , 2003, Trends in immunology.

[10]  C. Vedeler,et al.  Immunoglobulin G fc-receptor (FcgammaR) IIA, IIIA, and IIIB polymorphisms related to disease severity in rheumatoid arthritis. , 2002, The Journal of rheumatology.

[11]  M. Hartmann,et al.  S100A12 Is Expressed Exclusively by Granulocytes and Acts Independently from MRP8 and MRP14* , 1999, The Journal of Biological Chemistry.

[12]  C. Heizmann,et al.  Amino acid sequence determination of human S100A12 (P6, calgranulin C, CGRP, CAAF1) by tandem mass spectrometry. , 1996, Biochemical and biophysical research communications.