DECREASED LEVELS OF A SOLUBLE FORM OF THE HUMAN ADHESION RECEPTOR CD58 (LFA-3) IN SERA AND SYNOVIAL-FLUIDS OF PATIENTS WITH RHEUMATOID-ARTHRITIS

Objective. Soluble forms of adhesion molecules (sAM) can block cellula r interactions and potentially prevent the adhesion of mononuclear cel ls to inflammatory tissue. We therefore wondered whether levels of a s oluble form of the CD2-ligand CD58 (sCD58) are decreased in patients w ith different types of joint disease. Methods. SCD58 concentrations we re measured by an enzyme-lirzked immunosorbent assay (ELISA) of sera f rom 60 patients with rheumatoid arthritis (RA), 13 patients with osteo arthritis (OA) 16 patients with psoriatic arthropathy (PsA), 15 patien ts with spondylarthropathy (SpA) and 61 age-matched normal controls (N C). SCD58 was also determined in synovial fluid samples (SF) from 42 p atients with RA, 12 with PsA, and 12 with SpA. Concentrations of sCD58 were correlated with clinical and laboratory measures of disease acti vity. Binding of biotinylated human albumin to recombinant CD58 or cas ein was assessed by a modified ELISA. Results. SCD58 levels were signi ficantly reduced in sera from RA patients compared to NC (p < 0.0001), OA (p = 0.019), and SpA (p < 0.0001). Normal concentrations were foun d in sera from patients with OA, PsA, or SpA. SF sCD58 concentrations were generally lower than serum concentrations (between 18 and 28%). R A SF had significantly lower sCD58 levels than SpA SF (p = 0.01). Redu ction of serum sCD58 levels correlated significantly with the ESR (r = 0.56; p < 0. 0001), CRP (r = 0.4; p = 0.003), and TJS (r = 0.47; p = 0. 0001). In addition, sCD58 serum levels correlated significantly wit h the reticulocyte count (r = 0.47; p = 0. 02) and serum albumin (r = 0. 42; p = 0.002). Accordingly, biotinylated human albumin bound to re combinant CD58 in a dose dependent fashion, but not to casein. Conclus ion. This study indicates that serum and SF sCD58 levels inpatients wi th RA are reduced compared to the levels in normal controls and patien ts with OA or SpA. Decreased albumin concentrations due to systemic in flammation may lead to reduced sCD58 levels. Since sCD58 may normally mediate de-adhesion, such a reduction could result in increased T cell adhesiveness.