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


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Wong
C K
CK
Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
Lit
L C W
LC
Tam
L S
LS
Li
E K
EK
Lam
C W K
CW
D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis* / Q000097:blood; D000943:Antigens, Differentiation / Q000096:biosynthesis* / Q000097:blood; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000097:blood; D051940:B7-2 Antigen; D015415:Biomarkers / Q000097:blood; D018106:CD28 Antigens / Q000096:biosynthesis / Q000097:blood; D060908:CTLA-4 Antigen; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000097:blood; D008875:Middle Aged; D008934:Mitogens / Q000276:immunology; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D015415:Biomarkers; D018106:CD28 Antigens; C497964:CD86 protein, human; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D008562:Membrane Glycoproteins; D008934:Mitogens