Arthritis Manifestations Differ in RA and OA Patients

July 10, 2019

Anne-Mari Mustonen and colleagues in Finland have determined the respective fatty acid (FA) signatures found in the infrapatellar fat pad (IFP) and synovial fluid (SF) of patients with osteoarthritis (OA), and rheumatoid arthritis (RA). While the authors’ findings are inconclusive, they give insight into the complex alterations in fatty acid profiles found in knee arthropathies. They present their findings in a recent Arthritis Research & Therapy.

Anne-Mari Mustonen and colleagues in Finland have determined the respective fatty acid (FA) signatures found in the infrapatellar fat pad (IFP) and synovial fluid (SF) of patients with osteoarthritis (OA), and rheumatoid arthritis (RA). While the authors’ findings are inconclusive, they give insight into the complex alterations in fatty acid profiles found in knee arthropathies. They present their findings in a recent Arthritis Research & Therapy.

Adipocytes have been implicated in the inflammatory process and are present in the infrapatellar fat pad of the knee. It has been suggested that this extra-synovial organ may be a source of fatty acids (FA), FA-derived lipid mediators (LM), and adipocytokines that may play a role in knee arthropathies.

It is already known that the IPF is able to produce inflammatory mediators such as cytokines and cartilage-degrading enzymes and with its close proximity to the knee joint space there is a suggested link between the fat pad and joint pathology.

OA and RA have similarities and differences with regards to knee joint disease. Knee synovial fluid (SF) also contains clues to the pathophysiology behind joint destruction and progressive arthropathy. It is known that the concentrations in the SF of cholesterol, lipoproteins and apolipoproteins are elevated in RA while sphingolipids and glycerol-PL are elevated in both OA and RA.

It is further known that different types of polyunsaturated fatty acids (PUFA) have either pro-inflammatory (n-6 PUFA) or anti-inflammatory properties (n-3 PUFA). The interplay and implications of the various fatty acids remain controversial with some appearing protective in certain circumstances and detrimental in others.

Because studies focusing on a detailed assessment of FA signatures in RA and OA are few, the authors sought to assess the contribution made by the IFP to knee arthropathies by looking at the proportions of fatty acids in the fat pad and synovial fluid in the knees of patients with OA and RA.

The Study

Patients with knee joint disorders were recruited and included 10 patients with RA and 10 patients with OA. The patients selected were scheduled to undergo knee surgery for pre-existing conditions. IFP and SF samples were taken during joint replacement surgery. The experimental samples were compared to control SF samples collected from healthy subjects during arthroscopic knee surgery following knee trauma without OA or RA. All samples were analyzed for FA composition.

The Results

  • RA SF had higher proportions of mono-unsaturated fatty acids (MUFA) compared to control SF.

  • OA SF had higher levels of  total MUFAs while total poly-unsaturated fatty acids (PUFA), and total n-6 PUFA were reduced. The product/precursor ratios for these fatty acids were also reduced in OA SF.

  • Within the IFA in patients with RA, higher proportions of  total PUFA, and n-6 PUFA, were found along with decreased product/precursor ratios of n-3 PUFA.

  • The n-3/n-6 PUFA ratios of SF correlated positively with the n-3/n-6 PUFA ratios of IFP in RA patients (p < 0.0004) but not in OA patients (p = 0.580).

  • The n-3 PUFA sums correlated positively between SF and IFP in RA patients (p = 0.022) but not in OA patients (p = 0.365), and the 18:1n-9 proportions correlated between SF and IFP in OA patients (p = 0.043) but not in RA patients (p = 0.365).

Take-Home Points for Clinicians and Final Thoughts

The results indicate that n-6 PUFA is reduced in RA SF and especially in OA SF when compared to SF in control knees.
The product/precursor ratios of n-3 PUFA are decreased in OA SF compared to control knee SF.

Finally, the total n-6 PUFA, and product/precursor ratios of n-3 PUFA were lower in RA IFP than in OA IFP.

Contrary to the authors’ primary hypothesis, the classically pro-inflammatory n-6 PUFA was actually reduced in the SF of both RA and OA patients. This lends support to theories that reduced levels of pro-inflammatory FAs in the SF may be a response to inflammation rather than the cause of it.

The presence of higher MUFA proportions in both RA and OA support prior research implicating long-chain MUFAs in both diseases processes.
Clinically speaking, these data are confusing. It is difficult for clinicians to make sense of molecular mysteries with numeric nomenclature while striving to treat patients with knee pain. It is important, however, that this work be done and reported.

The authors reveal that clear differences exist between fatty acids found in the IFPs and SF of patients with OA and RA. While these differences have yet to be discovered implications for prognosis and treatment, they provide breadcrumbs for future researchers to follow in an effort to help our patients with OA and RA live better lives.

Reference:
Anne-Mari Mustonen, Reijo Kakela, Petri Lehenkari, et al. Distinct fatty acid signatures in infrapatellar fat pad and synovial fluid of patients with osteoarthritis versus rheumatoid arthritis.  Arthritis Research & Therapy (2019) 21:124 https://doi.org/10.1186/s13075-019-1914-y