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Urokinase plasminogen activator (uPA) catalyses the formation of the proteolytic enzyme plasmin, which plays a part in tissue degradation and remodelling,1 and seems to have an important role in the erosive growth of pannus in rheumatoid arthritis (RA).2 The action of uPA is localised and intensified by a cell bound receptor (uPAR),3 expressed by some malignant cells and some inflammatory cell types, including activated synoviocytes in the marginal zone between pannus and cartilage in RA synovial tissue.4
The uPAR may become cleaved at the cell surface bound anchor, forming a free soluble receptor (suPAR) which is detectable in steady, low concentrations in healthy controls, but with raised concentrations in patients with disseminated malignant disease.5
Recently, in a cross sectional study, we found increased concentrations of suPAR in plasma of patients with RA compared with controls and patients with other types of inflammatory rheumatic disorders.6 This finding raises the question, whether suPAR might be an easily accessible plasma marker of erosive activity in the synovial joint space in RA.
In a pilot study we followed up outpatients with RA to evaluate the relation between suPAR and disease activity. Plasma suPAR was measured and other clinical and paraclinical variables of disease activity deter-mined in these patients on two or more occasions during a 12 month period. The present study included all patients (n=16) for whom comparable radiographs of the wrists and hands were obtainable, and also, when relevant, other symptomatic joints, taken before and after the period of suPAR measurements. The x ray films of participating patients were read independently by a radiologist unaware of the patient's clinical status and suPAR values. An enzyme linked immunoabsorbent assay (ELISA) was used to measure suPAR in plasma, as previously described.5 ,6
The study group comprised 11 women and five men with a median age of 53.5 years (range 25–80) and a median disease duration of 57 months (range 5–360). Fifteen patients were rheumatoid factor positive and 10 had bony erosions on prestudy radiographs. Antirheumatic treatment included methotrexate (11 patients), hydroxychloroquine (two), sulfasalazine (one), and low dose steroids (eight). Clinical evaluation and measurement of suPAR, erythrocyte sedimentation rate (ESR), and C reactive protein (CRP) were done a median number of three times, and the time interval between radiographs was a median of 22 months.
Table 1 shows the results of the study. We found significantly higher suPAR concentrations (p<0.05) in plasma from those patients with RA whose x ray findings showed disease progression than in the patients who had no radiographic signs of progression, but the differences in ESR, CRP, and clinical variables were not significantly different.
This study was a pilot study in a clinical setting and conclusions must be drawn cautiously. The main problems, apart from the small number of patients, are, firstly, that in some of the patients prestudy radiographs were one to two years old. However, this would tend to diminish the differences found between the erosive progressive and non-erosive progressive groups as patients in remission, or with low activity in the study period, could be classified as progressive due to previous activity. Secondly, another possible bias, tending to increase the difference in suPAR between the two groups in this study, is that patients with high clinical activity would probably have had more extensive x ray examinations, increasing the chance of finding new erosions. We did not, however, find a difference in the number of radiographically investigated joints between our two groups of patients.
In conclusion, we find that this study indicates that plasma suPAR may be an easily accessible plasma marker of erosive progression in RA, and further studies on the subject are warranted.