Ring trial enables establishment of ceramide reference values

Espoo, Finland – [Oct. 3rd, 2024] – Results of the first phase of a Ceramide Ring Trial have just been published in the renowned journal Nature Communications, representing a significant landmark in the field of lipidomics. This achievement, coordinated by researchers at the University of Vienna and scientific teams in Singapore, Julich and Espoo, represents a groundbreaking advance in the establishment of ceramide reference values, plasma lipids involved in such as cardiovascular diseases. The ring trial was performed under the umbrella of the International Lipidomics Society (ILS) and its interest group on “Reference Materials and Biological Reference Ranges”.

Figure 1: The International Lipidomics Society’s standardization and harmonization efforts. Through cooperative efforts across 26 countries in reporting, lipid name harmonization, and lipid analysis, we increase data comparability across studies and labs, promoting more transparency and sustainability in science.

Lipidomics – the large-scale study of pathways and networks of cellular lipids in biological systems – aims to understand the roles of lipids in health and disease by analyzing their structures, functions, and interactions in cells. Understanding the upper and lower concentration boundaries of lipids is essential for scientific progress and the translation of technology within lipidomics. To do this, the Ceramide Ring Trial was initiated as the first step in addressing technical replication across a global network of laboratories.

A long term-trial…

A ring trial is a method where multiple laboratories independently analyze the same samples using similar or different methods to compare their results. It helps assess the reliability and consistency of measurements across different labs, improving standardization and quality control in scientific testing. After seven years of collaborative efforts, the results from 34 participating laboratories across 19 countries have been summarized in the Ceramide Ring Trial study. To maintain a strict focus while reducing complexity, the Ceramide Ring Trial concentrated on human plasma/serum and aimed to investigate concentration levels and their variabilities of four distinct ceramide lipid species. Ceramides are players in multiple diseases and have been associated as biomarkers in cardiovascular diseases. Participants of the trial utilized a preferred analytical method and/or a standardized protocol to quantify ceramides in NIST1950 (a standard reference material of metabolites in human plasma provided by the National Institutes of Standards and Technology, NIST) and three additional NIST pooled plasma reference materials, by using specially formulated mixtures of ceramide standards from Avanti Polar Lipids.

…with promising results

Figure 2: The core coordination team of the ring trail. From left to right Nils Hoffmann, Bo Burla, Kim Ekroos, Markus Wenk, Robert Ahrends, Federico Torta. 

“A number of valuable lessons can be learned from the results of our interlaboratory comparison,” explain the members of the coordination team of the ring trial: 1) Standardizing is key to reduce variations in the test procedure and reach consensus in the concentrations of the analytes of interest. 2) Obtaining mean absolute concentration levels of ceramides sets the baseline for future biological and medical studies relevant to ceramide-associated diseases. 3) By comparing mixed plasma samples, the study estimates the biological differences between healthy people, those with high cholesterol, and different ethnic groups. The team further adds: “This study, the largest and most targeted public inter-laboratory and cross-platform ring trial for distinct ceramides in human plasma, sets a new benchmark for future harmonization of lipidomics research and beyond. We extend our deepest gratitude and congratulations to all participants involved in this pioneering effort”.

References:

  1. Concordant inter-laboratory derived concentrations of ceramides in human plasma reference materials via authentic standards
    Federico Torta, Nils Hoffmann, Bo Burla, Irina Alecu, Makoto Arita, Takeshi Bamba, Steffany A. L. Bennett, Justine Bertrand-Michel, Britta Brügger, Mónica P. Cala, Dolores Camacho-Muñoz, Antonio Checa, Michael Chen, Michaela Chocholoušková, Michelle Cinel, Emeline Chu-Van, Benoit Colsch, Cristina Coman, Lisa Connell, Bebiana C. Sousa, Alex M. Dickens, Maria Fedorova, Finnur Freyr Eiríksson, Hector Gallart-Ayala, Mohan Ghorasaini, Martin Giera, Xue Li Guan, Mark Haid, Thomas Hankemeier, Amy Harms, Marcus Höring, Michal Holčapek, Thorsten Hornemann, Chunxiu Hu, Andreas J. Hülsmeier, Kevin Huynh, Christina M. Jones, Julijana Ivanisevic, Yoshihiro Izumi, Harald C. Köfeler, Sin Man Lam, Mike Lange, Jong Cheol Lee, Gerhard Liebisch, Katrice Lippa, Andrea F. Lopez-Clavijo, Malena Manzi, Manuela R. Martinefski, Raviswamy G. H. Math, Satyajit Mayor, Peter J. Meikle, María Eugenia Monge, Myeong Hee Moon, Sneha Muralidharan, Anna Nicolaou, Thao Nguyen-Tran, Valerie B. O’Donnell, Matej Orešič, Arvind Ramanathan, Fabien Riols, Daisuke Saigusa, Tracey B. Schock, Heidi Schwartz-Zimmermann, Guanghou Shui, Madhulika Singh, Masatomo Takahashi, Margrét Thorsteinsdóttir, Noriyuki Tomiyasu, Anthony Tournadre, Hiroshi Tsugawa, Victoria J. Tyrrell, Grace van der Gugten, Michael O. Wakelam, Craig E. Wheelock, Denise Wolrab, Guowang Xu, Tianrun Xu, John A. Bowden, Kim Ekroos, Robert Ahrends & Markus R. Wenk
    Nat Commun 15, 8562 (2024). https://doi.org/10.1038/s41467-024-52087-x