Antibodies to fibrin bound tissue type plasminogen activator in systemic sclerosis

Abnormalities of tissue type plasminogen activator (tPA) and plasminogen activator inhibitor have been described in some patients with systemic sclerosis (SSc). We studied 128 unselected SSc sera for the presence of autoantibodies to fibrin bound tPA.

A solid phase fibrin-tPA immunoassay utilized 500 IU/ml tPA bound to solid phase fibrin. Sera diluted 1/50 were incubated with the fibrin bound tPA, the plates were washed, and bound immunoglobulins were detected using polyvalent peroxidase labelled goat antihuman immunoglobulins. Controls included plates coated with fibrin alone or tPA passively adsorbed to the plastic. Sera were considered positive when the A490/630 was above the mean + 2 SD (> 0.055) obtained with normal human serum in 2 independent tests.

25/128 (20%) SSc sera demonstrated antibody reactivity with fibrin bound tPA (mean A490/630 = 0.112). Detailed clinical data were available on 117/128 patients with SSc and on 21/25 anti-tPA positive patients. The mean age of the anti-tPA positive group was 51 yrs and of the anti-tPA negative group 49.6 yrs. Within the anti-tPA positive group there was a significantly higher proportion (p > 0.05) of patients with the CREST (calcinosis, Raynaud's esophageal dysmotility, sclerodactyly, telangiectasias) variant of SSc (7/25 = 28% vs 11/103 = 11%) and pulmonary hypertension (5/21 = 24% vs 6/96 = 6%).

Our study demonstrates that 20% of unselected patients with SSc have anti-tPA antibodies and that there is a higher representation of patients with CREST syndrome in this subgroup. The high frequency of pulmonary hypertension in the anti-tPA positive group suggests that these autoantibodies may play a pathogenic role in certain patients with SSc.