Associations of plasma YKL-40 concentrations with heel ultrasound parameters and bone turnover markers in the general adult population.

OBJECTIVE: YKL-40, also known as chitinase-3-like protein 1, is a new proinflammatory biomarker, that might play a role in tissue remodeling and bone resorption. Here we evaluated the associations of the YKL-40 plasma concentration with heel ultrasound parameters and bone turnover markers (BTMs) in adult men and women from the general population. We tested for a causal role of YKL-40 on bone metabolism using published single nucleotide polymorphisms (SNPs) with consequences for YKL-40 expression and function. METHODS: Data were obtained from two population-based cohorts: the Study of Health in Pomerania (SHIP) and SHIP-Trend. Quantitative ultrasound (QUS) measurements at the heel were performed and bone turnover was assessed by measurement of intact amino-terminal propeptide of type I procollagen (PINP) and carboxy-terminal telopeptide of type I collagen (CTX). Associations between the YKL-40 plasma concentration and the QUS-based parameters, bone turnover marker (BTM) concentrations and 44 SNPs, including the lead SNP rs4950928, were evaluated in 382 subjects. Furthermore, we assessed the associations between the same SNPs and the QUS-based parameters (n = 5777) or the BTM concentrations (n = 7190). RESULTS: Sex-specific linear regression models adjusted for a comprehensive panel of interfering covariantes revealed statistically significant inverse associations between YKL-40 and all QUS-based parameters as well as positive associations with CTX in women. The rs4950928 polymorphism was associated with YKL-40 in men and women but none of the tested SNPs was associated with the QUS-based parameters or the BTMs after correction for multiple testing. CONCLUSIONS: Plasma YKL-40 concentrations are associated with QUS-based parameters as well as CTX concentrations in women but these associations are probably not causal.

Technical report: xMAPr - High-dynamic-range (HDR) quantification of antigen-specific antibody binding.

Here, we demonstrate a high-dynamic-range quantification of antibody binding to single antigens in a multiplexed suspension bead array format. Using a dilution-based approach and the newly developed data analysis tool the quantitative dynamic range is increased by three orders of magnitude in the selected samples. The strong increase in dynamic range results in a more robust data basis for downstream analyses.

Contact activation in low-density lipoprotein apheresis systems.

BACKGROUND: Anaphylactoid reactions due to contact activation have been observed in patients on ACE inhibitor therapy and hemodialysis with negatively charged dialysis membranes. Negatively charged surfaces are functional constituents of different LDL apheresis systems. Therefore, contact activation was investigated during LDL apheresis with three different systems: (i) heparin-induced extracorporeal LDL precipitation (HELP); (ii) dextran sulfate cellulose (DSC) columns; and (iii) modified polyacrylate gels (DALI) in a clinical setting. METHODS: 24 prevalent patients on regular LDL apheresis treatment were included in the study. Bradykinin, prekallikrein, and HMW kininogen were measured during a single LDL apheresis at different sites of the systems. RESULTS: LDL apheresis with DSC and DALI was associated with an extreme release of bradykinin after the passage of plasma or blood through the LDL adsorbers as well as with a decrease of prekallikrein and HMW kininogen during the course of the treatment. Bradykinin release exceeded the degradation capacity of the kininase II, since markedly elevated bradykinin concentrations were observed in the arterial line of the extracorporeal circuits of both systems. This was not associated with anaphylactoid reactions. In contrast to the treatments with DSC and DALI, the HELP system did not lead to any activation of the kallikrein-kinin system. CONCLUSION: From our data we conclude that angiotensin converting enzyme (ACE) inhibitors are contraindicated in patients on LDL apheresis with the DSC and the DALI system. Because the HELP system does not activate the kallikrein-kinin system, patients who need ACE inhibitors are predisposed for this LDL apheresis procedure.