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Anti-endothelial cell IgG fractions from systemic lupus erythematosus patients bind to human endothelial cells and induce a pro-adhesive and a pro-infiammatory phenotype in vitro

E Raschi

Department of Internal Medicine; Division of Nephrology and Dialysis-IRCCS Policlinico, University of Milan and Servizio di Immunologia Clinica, Spedali Civili, Brescia, Italy

G Moroni

Division of Nephrology and Dialysis-IRCCS Policlinico, University of Milan and Servizio di Immunologia Clinica, Spedali Civili, Brescia, Italy

P Panzeri

M O Borghi

Department of Internal Medicine; Division of Nephrology and Dialysis-IRCCS Policlinico, University of Milan and Servizio di Immunologia Clinica, Spedali Civili, Brescia, Italy

C Ponticelli

Division of Nephrology and Dialysis-IRCCS Policlinico, University of Milan and Servizio di Immunologia Clinica, Spedali Civili, Brescia, Italy

A Tincani

G Balestrieri

Servizio di Immunologia Clinica, Spedali Civili, Brescia, Italy

P L Meroni

Department of Internal Medicine; Division of Nephrology and Dialysis-IRCCS Policlinico, University of Milan and Servizio di Immunologia Clinica, Spedali Civili, Brescia, Italy

Affinity purified immunoglobulin G (IgG) fractions from systemic lupus erythematosus (SLE) patients positive for anti-endothelial cell antibodies (AECA) bind human umbilical vein endothelial cell (HUVEC) monolayers. In vitro incubation of serial protein concentrations of SLE AECA IgG induces a dose-dependent endothelial activation: i) increase of functional adhesion of the monocytic cell line U937; ii) upregulation of E-Selectin, ICAM-1, VCAM-1 expression evaluated by a cell solid-phase enzyme linked immunoassay; and iii) increased secretion of interleukin (IL)-6 in the culture supernatants. Control experiments carried out with HUVEC monolayers incubated with IgG fractions from normal healthy controls or from AECA negative SLE sera do not affect at all endothelial adhesion molecule expression or pro-inflammatory cytokine secretion. The AECA IgG effects are not related to both anti-phospholipid or anti-DNA activities.

Taken together the findings suggest that these autoantibodies might be important in recruiting and in activating mononuclear leukocytes responsible for vessel wall infiltration and raise the possibility that AECA might display a pathogenic role in SLE vessel damage.

Key Words: systemic lupus erythematosus • anti-endothelial cell antibodies • adhesion molecules • cytokines

Lupus, Vol. 8, No. 6, 423-429 (1999)
DOI: 10.1177/096120339900800603


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