Aberrant production of soluble costimulatory molecules CTLA-4, CD28, CD80 and CD86 in patients with systemic lupus erythematosus.

Abstract

The costimulatory interactions of the B7 family molecules CD80 and CD86 on antigen-presenting cells with their T-cell counter-receptors CD28 and CTLA-4 modulate T lymphocyte-mediated immune responses in a reciprocal manner. We investigated the possible aberrant production of soluble (s) forms of the T-cell costimulatory molecules CD80, CD86, CD28 and CTLA-4 in plasma of patients with systemic lupus erythematosus (SLE), an autoimmune disease arising from T-lymphocyte dysregulation. Plasma concentration and ex vivo production of soluble costimulatory molecules of 79 SLE patients with or without active disease and 40 sex- and age-matched healthy subjects were measured by enzyme-linked immunosorbent assay. Plasma sCTLA-4, sCD28, sCD80 and sCD86 concentrations of all SLE patients were significantly higher than concentrations in control subjects (all P<0.01). These increases were observed even in patients with inactive disease [SLE Disease Activity Index (SLEDAI) <3]. Plasma sCTLA-4 concentration in all SLE patients correlated significantly with SLEDAI score (r = 0.228, P = 0.043). Upon mitogen treatment of peripheral blood mononuclear cells, the percentage increases in ex vivo production of sCD28 and sCD80 and the percentage decrease in sCTLA-4 release were all significantly smaller in SLE patients with active disease than in healthy subjects (P<0.01, P<0.05 and P<0.0001, respectively). The aberrant production of soluble T-cell costimulatory molecules is important in the immunopathogenesis of SLE, which occurs by the dysregulation of T-lymphocyte costimulation. Plasma sCTLA concentration could potentially serve as a surrogate marker of SLE disease activity.