Increased n-6 polyunsaturated fatty acids indicate pro- and anti-inflammatory lipid modifications in synovial membranes with rheumatoid arthritis.

Mustonen A, Tollis S, Käkelä R, Sihvo SP, Palosaari S, Pohjanen V, Yli-Hallila A, Lehenkari P, and Nieminen P. (2023) Increased n-6 polyunsaturated fatty acids indicate pro- and anti-inflammatory lipid modifications in synovial membranes with rheumatoid arthritis. Inflammation

Inflammatory joint diseases affect the soft tissue lining of synovial joints, the fibrous joint capsule that joins bones or cartilage. This lining is called the synovial membrane and it is specialized connective tissue that lines the inner surface of the joint capsules. This lining layer consists of macrophage-like synoviocytes and fibroblast-like synoviocytes (FLSs). The FLSs produce components of synovial fluid which lubricate articular cartilage surfaces. In addition to its purpose as a lubricant, synovial fluid also contains nutrition for chondrocytes, cells found in cartilage that maintain the cartilaginous matrix, and macrophages which protect from bacterial infection and help clear debris. Lipids make up the majority of the synovial membrane and interestingly, phospholipid synthesis is known to be stimulated in inflammatory conditions. Under inflammatory conditions, the synovial membrane thickens due to macrophage and lymphocyte infiltration, neovascularization, hyperplasia, and fibrosis. As well, FLSs increases production of cytokines, nitric oxide, prostaglandin E2 and cartilage-degrading proteinases which results in synovitis (inflammation of the synovial membrane), joint swelling, pain, and degradation of the cartilage extracellular matrix. In rheumatoid arthritis, the synovial membrane is transformed to a pannus-like structure which attaches to the cartilage surface, then invades and degrades the cartilage and bone. As well, in rheumatoid arthritis the composition of synovial fluid is altered which may impact its lubricative properties. Mustonen et al were interested in determining the fatty acid (FA) composition in the synovial membranes of people previously diagnosed with rheumatoid arthritis and osteoarthritis.

To determine if the fatty acid composition differs between the inflammatory states of rheumatoid arthritis and osteoarthritis, fatty acids were extracted from synovial membranes, identified, and quantified. This data was then used in a discriminant analysis by classifying individual fatty acid data by discriminant functions to show how the rheumatoid arthritis and osteoarthritis were different from one another. When looking at the FAs in the two patient groups, there were some distinct sets of FAs found suggesting that it could be possible to find groups of FAs with consistent associations with either disorder. To confirm this, a hierarchical clustering analysis was used to test FAs from rheumatoid arthritis and osteoarthritis synovial membranes and found biologically meaningful groups of FAs with similar patterns across diagnoses, high intra-group similarity, and lower inter-group similarity. To determine if these FA profiles could be used functionally to classify the diagnoses, a random forest (RF) model based on partial data from each variable group was created. When trying to predict health status of the samples, the RF model predicted 99.8% of testing data and demonstrated that even partial FA profiles were sufficient to predict the health status of other partial profiles. The FA groups found to be most important in classification by the RF model were C14-C16 saturated FAs, DMA 16:0, and saturated FA sum.

Mustonen et al were interested in establishing the difference in FA composition between patients with rheumatoid arthritis and osteoarthritis. They found that there is a difference in FAs present and their levels between the two arthritis types. This difference was great enough that even partial FA profiles could be used to correctly diagnose the samples 99.8% of the time, with saturated FAs and 20:3n-6 being the most important for distinguishing between the two. Further work looking into FAs and other lipids in inflammatory diseases would be useful in understanding their pathologies and possibly in the development of new diagnostic tools.