Session Information
Session Title: Imaging in Rheumatoid Arthritis
Session Type: Abstract Submissions (ACR)
Background/Purpose: Synovitis and bone damage may represent two distinct but overlapping pathological processes in rheumatoid arthritis (RA). Whereas the bulk of synovial cells contribute to general joint inflammation, the interplay between synovial cells, neighboring cartilage and bony tissue at the margins of the joint contribute to bone degradation(1). The aim of this study was investigate if the levels of inflammatory cytokines interleukine 6 (IL-6), interleukine 8 (IL-8), macrophage chemo-attractant protein 1 (MCP-1) and macrophage inflammatory protein 1 beta (MIP-1b), which all play key roles in RA pathology, correlate with disease intensity and/or can discriminate between key pathological processes in RA.
Methods: Fifty-seven synovial sites from the hand joints of twenty-five RA patients were evaluated by color Doppler ultrasound (CDUS, 52 synovial sites) and/or high field magnetic resonance imaging (MRI, 39 synovial sites) and subsequently synovectomized by a needle-arthroscopic procedure. Synovial tissue was cultured for 72h, and the concentration of Il-6, Il-8, MCP-1 and MIP-1b in the culture supernatants were measured by Multiplex immunoassays. Ultrasound Doppler was determined as the color fraction. MRI bone marrow edema, synovitis, and erosion score were estimated by the rheumatoid arthritis magnetic resonance score [RAMRIS]. The concentrations of inflammatory mediators were compared to imaging data from the individual sites using repeated samples from the same patients. Since data was clustered within patients, a mixed linear model was applied for the statistical analysis. Parsimony in the statistical model was achieved omitting covariates with (P>0.1) from the model.
Results: Ultrasound color fraction and the RAMRIS synovitis score were statistically associated with the release of MCP-1 (P=0.004 and P=0.04, respectively), IL-8 (P=0.04 and P=0.04, respectively), and MIP-1b (P=0.01 and P=0.05, respectively), but not with IL-6 (P=0.29 and P=0.21, respectively). IL-6 was the only supernatant mediator, which was associated to the RAMRIS erosion component (P=0.002). There were no statistically significant associations between mediator release and the RAMRIS bone marrow edema component: MCP-1(P=0.07), IL-6 (P=0.93), IL-8 (P=0.40) and MIP-1b (P=0.96).
Conclusion: Levels of IL-8, MCP-1, MIP-1b were significantly associated with clinical assessment of synovitis, but not bone erosion, indicating that these molecules play key roles in general inflammation in the joint, and underlining their potential as biomarkers to measure levels of synovitis. In contrast, levels of IL-6 significantly associted with clinical assessment of bone erosion, indicating that this cytokine, which is known to have direct activating effects on osteoclasts, has potential as a biomarker for measuring bone destructive activity in RA patients.
Acknowledgments: Supported by unrestricted grants from Novo Nordisk, The Danish Agency for Science Technology and Innovation and the Oak Foundation.
References:
(1) Lafeber FP, Van der Laan WH. Progression of joint damage despite control of inflammation in rheumatoid arthritis: a role for cartilage damage driven synovial fibroblast activity. Ann Rheum Dis 2012; 71(6):793-5.
Disclosure:
M. Andersen,
Novo Nordisk,
3;
M. Boesen,
None;
K. Ellegaard,
None;
R. Christensen,
Abbott, Axellus A/S, Bristol-Myers Squibb, Cambridge Weight Plan, Norpharma, Pfizer, and Roche,
5,
Axellus A/S, Cambridge Weight Plan, Mundipharma, and Roche,
2,
Abbott, Axellus, Bayer HealthCare Pharmaceuticals, Biogen Idec, Bristol-Myers Squibb, Cambridge Weight Plan, Ipsen, Laboratoires Expanscience, MSD, Mundipharma, Norpharma, Pfizer, Roche, and Wyeth,
8;
K. Söderström,
Novo Nordisk,
1,
Novo Nordisk,
3;
S. Torp-Pedersen,
None;
B. Danneskiold-Samsøe,
None;
E. M. Bartels,
None;
N. Vendel,
None;
N. H. Søe,
None;
P. Spee,
Novo Nordisk,
1,
Novo Nordisk,
3;
U. G. Mørch,
Novo Nordisk,
1,
Novo Nordisk,
3;
L. Karlsson,
Novo Nordisk,
1,
Novo Nordisk,
3;
H. Bliddal,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/synovial-explant-inflammatory-mediator-production-is-associated-with-synovitis-while-not-with-bone-marrow-edema-in-rheumatoid-arthritis-a-cross-sectional-study/