Article Text

PDF
OP0223 M-ficolin, an activator of the complement system, predicts DAS28 remission in early DMARD naïve rheumatoid arthritis
  1. C.G. Ammitzbøll1,
  2. J.C. Jensenius2,
  3. T. Ellingsen3,
  4. S. Thiel2,
  5. K. Hørslev-Petersen4,
  6. M. Hetland5,
  7. P. Junker6,
  8. J. Johansen5,
  9. M. Østergaard5,
  10. J. Pødenphant7,
  11. K. Stengaard-Pedersen1
  12. and the OPERA Study Group
  1. 1Aarhus University Hospital
  2. 2Aarhus University, Aarhus
  3. 3Silkeborg Regional Hospital, Silkeborg
  4. 4King Christian X’s Rheumatism Hospital, Gråsten
  5. 5Glostrup Hospital, Glostrup
  6. 6Odense University Hospital, Odense
  7. 7Gentofte Hospital, Gentofte, Denmark

Abstract

Background M-ficolin is a soluble pattern recognition molecule that activates the complement system. We recently reported a factor 300 difference in the synovial fluid M-ficolin concentration between rheumatoid arthritis (RA) and osteoarthritis, suggesting a pathogenic role of M-ficolin1.

Objectives To assess M-ficolin in DMARD naïve early RA patients, investigate correlations between M-ficolin and disease activity markers, and analyze the predictive value of M-ficolin.

Methods 180 DMARD naïve RA patients with disease duration <6 months were included in a randomized double blind placebo-controlled trial (OPERA) of methotrexate, intraarticular glucucorticoids + either adalimumab (ADA) or placebo (PLA). A sandwich-type time-resolved immunofluorometric assay using monoclonal antibodies was used for quantification of M-ficolin in the OPERA cohort, 101 healthy adults and 51 chronic RA patients in remission. Concentrations are reported as medians. Spearman test, Students T-test and one-way analysis of variance were used. Logistic regression analyses were performed and adjusted for CRP, treatment group (ADA/PLA), x-ray erosions, anti-CCP, IgM-RF, neutrophils and monocytes.

Results The highest M-ficolin levels were measured in the OPERA cohort at baseline (2.84μg/l, CI 2.63-3.09), and during treatment the level decreased 24% (CI 18-31%, p<0.001) at year one (2.31μg/l, CI 2.14-2.50). The healthy adults had significantly lower concentrations (1.88μg/l, CI 1.72-2.06) than the OPERA cohort at baseline (p<0.001) and year one (p<0.001), and the chronic RA patients (2.17μg/l, CI 1.94-2.42) (p=0.03).

At baseline M-ficolin correlated to DAS28 (rho=0.29, p<0.001) and the four variables constituting DAS28 (0.001< p≤0.04). At year one M-ficolin correlated to DAS28 (rho=0.36, p<0.001) and 3 of the 4 variables constituting DAS28 (0.001< p≤0.05), except tender joint count 28 (p=0.23). Furthermore M-ficolin correlated to HAQ at debut (rho=0.25, p=0.003) and year one (rho=0.23, p<0.001).

Logistic regression analysis determined M-ficolin as the strongest predictor of DAS28<2.6 at year one (coefficient=1.42, p=0.0001) followed by treatment group (PLA/ADA) (coefficient=1.23, p=0.001) and erosions on baseline x-ray (coefficient=-1.19, p=0.02), but M-ficolin was the only variable that predicted DAS28<3.2 at year one (coefficient=0.89, p=0.02).

Low baseline M-ficolin level was the only variable associated with low disease activity at year one, and this was further analyzed by comparing the group with the 25% lowest baseline M-ficolin levels with the remaining 75% of patients (cutoff 2.00 μg/l). This resulted in a sensitivity of 29%, a specificity of 96%, and a positive predictive value of 98% in determining a DAS28 score <3.2 at year one.

Conclusions The elevated baseline M-ficolin levels in early RA correlated consistently to disease activity markers, most notably DAS28 and HAQ, thus reflecting essential parts of the disease activity. Low M-ficolin levels at baseline predicts a positive predictive value of 98% of a DAS28<3.2 after one year irrespective of treatment and well-known prognostic factors.

  1. Ammitzbøll CG, et al. Rheumatol Int 2011.

Disclosure of Interest None Declared

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.