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Increased serum levels of microfibrillar-associated protein 4 (MFAP4) are not associated with clinical synovitis in rheumatoid arthritis but may reflect underlying cardiovascular comorbidity

1, 2, 3, 4, 5, 6, 7, 8, 9

 

  1. Department of Rheumatology, The Rheumatology Research Unit, Odense University Hospital and University of Southern Denmark, Odense, Denmark. saidaissa@gmail.com
  2. Department of Rheumatology, The Rheumatology Research Unit, Odense University Hospital and University of Southern Denmark, Odense, Denmark.
  3. Department of Rheumatology, Silkeborg Hospital, Silkeborg, Denmark.
  4. Department of Cancer and Inflammation, The Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
  5. Department of Rheumatology, Vejle Hospital, Vejle, Denmark.
  6. Research Unit at King Christian X Hospital for Rheumatic Diseases, Graasten, Denmark.
  7. Department of Cancer and Inflammation, The Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
  8. Department of Cancer and Inflammation, The Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
  9. Department of Rheumatology, The Rheumatology Research Unit, Odense University Hospital and University of Southern Denmark, Odense, Denmark.

CER12069
2020 Vol.38, N°1
PI 0122, PF 0128
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PMID: 31498068 [PubMed]

Received: 11/01/2019
Accepted : 15/04/2019
In Press: 27/08/2019
Published: 06/02/2020

Abstract

OBJECTIVES:
To study circulating MFAP4 in rheumatoid arthritis (RA) and its associations with clinical phenotype.
METHODS:
Early RA (ERA): 47 patients with newly diagnosed, treatment naïve RA were included. Serum MFAP4, clinical and laboratory disease variables were recorded serially during 12 months of intensive synovitis suppressive treatment. Long-standing RA (LRA): 317 patients participated, all receiving DMARD treatment. Disease activity, autoantibody status, extra-articular manifestations and cardiovascular morbidity were recorded. Paired serum and synovial fluid samples were obtained from 13 untreated ERA patients. Healthy blood donors served as reference points. MFAP4 was quantified by AlphaLISA immunoassay. Univariate, multivariate and mixed effects regression models were applied in the statistical analysis.
RESULTS:
ERA: MFAP4 increased from baseline and was significantly elevated at the 12-month follow-up, 17.8 U/l [12.6;24.1] vs. healthy controls, 12.7 U/l [9.5;15.6], p<0.001. MFAP4 did not correlate with joint counts or C-reactive protein. LRA: MFAP4 was increased, 25.9 U/l [20.4;33.7] vs. healthy controls, 17.6 U/l [13.7;21.2], p<0.0001, but did not correlate with disease activity measures or presence of extra-articular manifestations. Notably, MFAP4 correlated inversely with smoking (p<0.0001) and presence of antibodies against cyclic citrullinated peptides (anti-CCP), p=0.005. There was a positive association with systolic blood pressure, p=0.001 and co-occurrence of three cardiovascular events and/or risk factors, p<0.0001. The serum:synovial fluid MFAP4 ratio was 2:1.
CONCLUSIONS:
MFAP4 increases from diagnostic baseline despite intensive treatment but does not associate with synovitis at early or late stages of RA. Correlation patterns indicate that increased MFAP4 may reflect enhanced RA-related vascular remodelling.

Rheumatology Article