Metabolomic Analysis of Synovial Fluids from Rheumatoid Arthritis
Patients Using Quasi-Targeted Liquid Chromatography-Mass
Spectrometry/Mass Spectrometry
Abstract
Objective Synovial fluid (SF) accumulates extensively in joints of
individuals with rheumatoid arthritis (RA), which reflects the
pathological state of the synovium and disease activity. This study
applied quasi-targeted liquid chromatography-mass spectrometry/mass
spectrometry, an advanced metabolomics technique, to find characteristic
metabolism in RA. Methods SF samples from the patients (n=20) were
collected and examined using the metabolomic technique. SF samples from
patients with osteoarthritis (OA) (n=20) were used as controls. Results
Four hundred seventy nine variable metabolites were detected, and 250 of
these metabolites were identified by searching the Human Metabolome
Database (HMDB) and a self-constructed information list of possible
metabolites. S-plot and volcano plot analysis detected 22 metabolites
with differential levels in RA SF compared with those in OA SF. With
these 22 candidate metabolites, pathway analysis using the Kyoto
Encyclopedia of Genes and Genomes (KEGG) pathway database detected
upregulation of pyrimidine metabolism and purine metabolism, and
downregulation of fatty acid biosynthesis and unsaturated fatty acid
biosynthesis in RA SF. Receiver operating characteristic (ROC) analysis
and logistic regression models detected increased levels of guaiacol,
naringenin, phenylpropanolamine and vanillylmandelic acid in RA SF.
Furthermore, the naringenin level showed positive correlation with
rheumatic factor (RF) and anti-cyclic citrillinated peptides (anti-CCP)
levels. Conclusion Our study suggests disturbed pyrimidine metabolism,
purine metabolism, fatty acid biosynthesis and unsaturated fatty acid
biosynthesis as well as increased naringenin level are characteristic
metabolism in RA.