CORRELATION BETWEEN SERUM LEVELS OF SOLUBLE TUMOR-NECROSIS-FACTOR RECEPTOR AND DISEASE-ACTIVITY IN SYSTEMIC LUPUS-ERYTHEMATOSUS

Objective. To determine the value of measurement of serum soluble tumo r necrosis factor receptor (sTNFR), compared with established paramete rs such as anti-double-stranded DNA, in monitoring systemic lupus eryt hematosus (SLE) disease activity, and to determine whether serum sTNFR are bioactive and can effectively inhibit TNF bioactivity. Methods. F ifty-three consecutive ambulatory or hospitalized SLE patients and 140 consecutive healthy subjects were enrolled in a prospective cohort st udy. Serum levels of sTNFR were measured by a unique 2-sided capture e nzyme-linked immunosorbent assay using mouse monoclonal antibodies and rabbit antisera against the sTNFR. Results, The mean +/- SD concentra tions of both the p55 (type I) and p75 (type II) soluble receptors wer e significantly higher in a group of 46 SLE patients than in controls: 1.89 +/- 0.89 ng/ml versus 0.77 +/- 0.19 ng/ml and 7.25 +/- 3.89 ng/m l versus 3.02 +/- 0.57 ng/ml, respectively (P < 0.0001 for both). The incidence and the extent of the increase among the healthy subjects an d these patients (as well as in 7 additional patients on whom sequenti al studies were performed) correlated with disease activity more than did the occurrence of serum anti-DNA antibodies (correlation coefficie nts with disease activity 0.81 and 0.85 for p55 and p75 sTNFR, respect ively, and 0.51 for anti-DNA antibodies). The increase in sTNFR levels seems to reflect, largely, enhanced formation, and only to a minor ex tent, reduced clearance due to impairment of renal function. Sera of t he SLE patients had a marked inhibitory effect on the in vitro cytocid al activity of TNF, and this was shown to result entirely from their h igher sTNFR receptor concentration. Conclusion. An increase in serum l evels of sTNFR may become a useful marker for SLE activity since it sh ows a stronger correlation than do any other laboratory or clinical pa rameters employed presently in the daily clinical setting. At the conc entrations attained in the serum of SLE patients, sTNFR effectively in hibit the bioactivity of TNF and may thus be a significant determinant of the intensity of the manifestations of SLE.