Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose
In early rheumatoid arthritis (RA), clinical disease characterized by swollen and painful joints is caused by synovitis. However, presence of autoantibodies may precede the clinical onset of RA by several years, and joint damage can progress despite clinical remission. Therefore, early and aggressive synovitis suppression has become the principal goal in “treat-to-target” strategies. However, the temporal changes of immune system abnormalities during therapy and their significance remain poorly understood. Previously, we found a negative consequence of having low levels of the soluble form of CD18 (sCD18) in patients with chronic RA and spondyloarthritis1,2. Here, we study changes in plasma sCD18 levels in patients with early RA during a treat-to-target strategy (the OPERA regimen)3, during arthritogenesis in a murine model of chronic inflammatory polyarthritis (the SKG model) and in RA mononuclear cell cultures.
Methods
The level of sCD18 in plasma was analyzed with a time-resolved immunoflourometric assay in a study population of 152 patients with early treatment naïve RA at baseline and after 3, 6, and 12 months of treatment and during induced arthritogenesis in SKG mice. In vitro, synovial fluid mononuclear cells (SFMCs) and peripheral blood mononuclear cells (PBMCs) from 9 RA patients were cultured with either TNFα (40 ng/ml) or adalimumab (5μg/ml) for 48 hours. Data are expressed as median and IQR.
Results
Plasma levels of sCD18 were decreased in early RA patients at baseline (958.7 (766.2-1243) mU/ml) compared with healthy controls (HC) (1001 (872.0-1355) mU/ml) (P<0.05). The sCD18 plasma levels decreased further by 11% after 3 months (P<0.05), but after 12 months of treatment the levels returned to those of HC. The sCD18 increment between 3 and 12 months was most pronounced in patients who achieved an early ACR response compared with non-responders (P<0.05). Changes in plasma sCD18 between baseline and 12 months associated inversely with progression in total Sharpe score (rho=-0.18, P<0.05) and joint space narrowing (rho=-0.23, P<0.01) at the 24-month radiographic follow-up. Similarly, the serum level of sCD18 was decreased in SKG mice 6 weeks after arthritis induction (249 (151-282) mU/ml) compared with control SKG mice (334 (313-403) mU/ml) (P<0.05) and exhibited a biphasic course after arthritis induction with an initial increase above baseline (P<0.05) followed by a decline to levels below baseline (P<0.05). In vitro, shedding of CD18 from RA SFMC and RA PBMC cultures were increased 2-3 fold by TNFα (both P<0.01) and decreased by adalimumab (P<0.05 and P<0.01, respectively).
Conclusion
Concordant biphasic temporal patterns of sCD18 were observed in early RA and in a murine model of chronic inflammatory polyarthritis. The late increase in sCD18 was particularly pronounced in patients who achieved and early ACR response and may reflect latency in immune system restoration pertaining to the course of future radiographic progression.
References
1. Gjelstrup et al, J. Immunol., 2010.
2. Kragstrup et al, Arthritis Res Ther, 2014.
3. Hørslev-Petersen et al, ARD, 2013.
Disclosure:
T. W. Kragstrup,
None;
B. Jalilian,
None;
K. K. Keller,
None;
K. Stengaard-Pedersen,
None;
M. Lund Hetland,
None;
K. Hørslev-Petersen,
None;
P. Junker,
None;
M. Østergaard,
Abbott/Abbvie, Centocor, Merck, Schering-Plough,
2,
Abbott/Abbvie, BMS, Boehringer-Ingelheim, Eli-Lilly, Centocor, GSK, Janssen, Merck, Mundipharma, Novo, Pfizer, Schering-Plough, Roche UCB, Wyeth,
5;
E. M. Hauge,
None;
M. Hvid,
None;
T. Vorup-Jensen,
None;
B. Deleuran,
None.
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