Soluble urokinase plasminogen activator receptor in plasma of patients with inflammatory rheumatic disorders: increased concentrations in rheumatoid arthritis.
OBJECTIVE
Urokinase type plasminogen activator (uPA) catalyses the formation of the proteolytic enzyme plasmin, which is involved in matrix degradation in the processes of tissue remodelling. Because of a surface bound uPA receptor (uPAR), expressed by some cell types (for example, macrophages, malignant cells and inflammatory activated synoviocytes), the action of uPA can be localised and intensified. uPAR seems to have a role in the mechanisms leading to invasive growth of malignant tissue and the rheumatoid pannus. uPAR may become cleaved at its cell surface anchor, thus forming a free soluble receptor (suPAR). suPAR is detectable in low but constant values in plasma of healthy people, while increased concentrations are found in patients with disseminated malignant disease, so that suPAR may be an indicator of invasive growth and tissue remodelling. suPAR concentrations in plasma have not previously been measured in rheumatic patients. A controlled cross sectional measurement was performed of suPAR in plasma of patients with various inflammatory rheumatic disorders with special reference to rheumatoid arthritis (RA).


METHODS
suPAR in plasma was measured by ELISA technique in patients with RA (n=51), reactive arthritis (ReA) (n=23), primary Sjögren's syndrome (PSS) (n=42) and sex and age matched healthy controls (n=53).


RESULTS
In the control group suPAR (median) was 0. 91 (range 0.56-1.94) microg/l. Median suPAR value in RA was 1.47 (range 0.65-6.62) microgram/l; in ReA 0.68 microgram/l (range 0.52-1.48) and in PSS 1.12 microgram/l (range 0.76-1.92); p versus controls <0.001 in all patient groups. suPAR values in RA were also significantly increased compared with ReA (p<0.001) and PSS (p=0.004) groups. suPAR in RA was positively correlated to C reactive protein (CRP) (p<0.01) and erythrocyte sedimentation rate (p<0.05) and number of swollen joints (p<0.05). The ReA group had the highest CRP values of all groups, but at the same time the lowest suPAR concentrations in plasma.


CONCLUSIONS
Increased suPAR concentrations were found in plasma in RA, and to a smaller extent also in PSS, but not in ReA. In RA suPAR is related to disease activity. suPAR seems though not merely to be an acute phase reactant like CRP. Increased suPAR values might reflect erosive activity in RA.
Slot
O
O
Department of Rheumatology, Copenhagen County Hospital Gentofte, DK-2900 Hellerup, Denmark.
Brünner
N
N
Locht
H
H
Oxholm
P
P
Stephens
R W
RW
D000328:Adult; D000368:Aged; D016918:Arthritis, Reactive / Q000097:blood; D001172:Arthritis, Rheumatoid / Q000097:blood*; D003430:Cross-Sectional Studies; D004792:Enzyme Precursors / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010960:Plasminogen Activators / Q000097:blood*; D000091402:Prohibitins; D011956:Receptors, Cell Surface / Q000097:blood*; D055293:Receptors, Urokinase Plasminogen Activator; D012859:Sjogren's Syndrome / Q000097:blood; D012995:Solubility; D014568:Urokinase-Type Plasminogen Activator / Q000097:blood
D004792:Enzyme Precursors; C000717331:PHB2 protein, human; C524898:PLAUR protein, human; D000091402:Prohibitins; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator