Induction of endothelial cell apoptosis by IgG antibodies from SLE patients with nephropathy: a potential role for anti-endothelial cell antibodies.
Systemic lupus erythematosus (SLE) is a prototype of an autoimmune disease with vasculopathy as demonstrated by the presence of vascular immune-complex deposition, inflammation, and thrombosis. A pivotal role in the initiation of vasculopathy is ascribed to vascular endothelium. In this respect, anti-endothelial cell antibodies (AECA), which are highly associated with SLE, are putative candidates for the initiation of SLE vasculopathy. In addition to the potency of AECA to induce a proinflammatory endothelial cell phenotype, AECA have also been described to trigger endothelial cell apoptosis. However, in SLE data are not uniform on the potentials of AECA to induce endothelial cell apoptosis in vitro. We have addressed this question in a cohort of SLE patients with nephropathy. AECA levels, and the apoptosis-inducing potentials of serum IgG were measured at the time of renal complication and biopsy. Also serum antibody reactivity with various SLE-related autoantigens including HSP60 was determined in patients. The results show that the SLE patient group has increased AECA levels as well as increased levels of induction of endothelial cell apoptosis by serum IgG. AECA and apoptosis values largely varied among the patients. Our data show that antibodies other than anti-HSP60 are also involved in apoptosis induction. The results are discussed in the context of recent findings on the role of AECA in endothelial cell apoptosis and renal vasculopathy in SLE.
van Paassen
Pieter
P
Division of Clinical & Experimental Immunology, Department of Internal Medicine, CARIM, Academic Hospital and University of Maastricht, Maastricht, The Netherlands. p.vanpaassen@immuno.unimaas.nl
Duijvestijn
A
A
Debrus-Palmans
L
L
Damoiseaux
J
J
Vroomen
M
M
Tervaert
J W Cohen
JW
D017209:Apoptosis / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D018834:Chaperonin 60 / Q000276:immunology; D042783:Endothelial Cells / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008181:Lupus Nephritis / Q000276:immunology*
D001323:Autoantibodies; D001324:Autoantigens; D018834:Chaperonin 60; D007074:Immunoglobulin G; C087589:anti-endothelial cell antibody