gms | German Medical Science

Objectives: It is presumed that osteoarthritis (OA) progresses for over 20 years before it is detectable by radiological imaging. As such, biomarkers that reflect the molecular remodeling that occurs in the early stages of OA progression may provide a diagnostic tool which would enable an early treatment of OA. We recently could show that the human synovial fluid (SF) lipidome often differ between healthy individuals and the early and late stages of OA. In this line, we hypothesized that blood mirrors at least some of the alterations of SF lipidome during OA. Thus, in the current study we compared the lipidome of serum and SF obtained from healthy donors and patients with early or late stage OA knee joints.

Methods: Lipids were extracted from cell- and cellular debris-free knee SF and serum obtained from 16 postmortem (SF) and 33 (serum) joint-healthy donors, 49 patients with early and 43 patients with late OA changes. Extracted lipids were quantified using electrospray ionization tandem mass spectrometry. The general linear model analysis was applied to investigate possible effects of age, BMI, and gender on the level of lipids. Statistically significant differences in lipid concentrations between control and OA SF and serum were analyzed by paired t-test of the log-values. Statistical analysis was performed using program R. The present study was approved by the ethical review committee of our University.

Results and Conclusion: Human SF and serum have a comparable composition of lipid classes and species. The seven different lipid classes present in human SF and serum compromise 107 lipid species with the following species distribution: 28 phosphatidylcholine, 5 lysophosphatidylcholine, 16 sphingomyelin, 24 phosphatidylethanolamine based plasmalogen, 14 phosphatidylethanolamine, 11 phosphatidylinositol, and 9 ceramide species. Interestingly, the lipid levels were 4 to 10-fold elevated in serum and, approximately parallel to those of the SF. Some of the lipid species being elevated in OA SF are also elevated in OA serum obtained from the same donor. Importantly, with advanced disease stage more lipid species are found at elevated serum levels as compared to normal controls.

In conclusion, our lipidomic analysis is the first study which compares intraindividually a broad spectrum of phospholipid and sphingolipid species found in serum and SF of the same patients. Our quantitative data reveal that human serum often reflect the alterations in lipid species levels seen in SF of OA patients as compared to normal controls. Further studies with larger well characterized cohorts are needed to identify and verify individual lipid species as novel biomarkers to diagnose early stages of OA. Furthermore, stage dependent alterations of several serum lipid species might be used to monitor OA progression.