Circulating endothelial cells, endothelial apoptosis and soluble markers of endothelial dysfunction in patients with systemic lupus erythematosus-related vasculitis.
OBJECTIVE
Evidence is accumulating for endothelial cell dysfunction as one of the main factors initiating vessel wall damage in SLE. Enhanced expression of endothelial adhesion molecules is suggested to play a crucial role in the pathogenesis of vasculitis, while the number of circulating endothelial cells (CECs) is believed to be a reliable marker of endothelial damage. It therefore seems relevant to investigate CECs counts and soluble markers of endothelial dysfunction in SLE patients with inflammatory microangiopathy. The aim of this study was to assess the number of CECs, including apoptotic CECs, as well as to determine serum levels of sVCAM-1, sICAM-1 and sE-selectin in patients with SLE-related vasculitis.


METHODS
The study included 51 women with SLE, divided into 2 subgroups: I patients with severe disease activity according to SLEDAI score, developing vascular complications, such as central nervous system affection and/or vasculitis and/or glomerulonephritis, II patients with mild or moderate disease activity, without vascular complications. The control group consisted of 16 healthy female volunteers. CECs, including apoptotic CECs, were isolated using anti-CD146-coated immunomagnetic Dynabeads. Serum levels of sVCAM-1, sICAM-1 and sE-selectin levels were determined with ELISA.


RESULTS
In patients with SLE, CEC counts were significantly higher than in healthy controls, and strongly correlated with disease activity assessed by SLEDAI score. The number of apoptotic CECs, as compared with healthy subjects, increased considerably only in subgroup I. Serum sVCAM-1 levels were notably increased in subgroup I in relation to subgroup II and in subgroup II in relation to the control group, while serum sICAM-1 and sE-selectin levels in both subgroups were comparable and significantly higher than those of healthy subjects.


CONCLUSIONS
The study showed that the number of CECs increases in SLE and strongly correlates with disease activity, reaching maximum values at the stage of inflammatory microangiopathy-related complications. Severe SLE flares are characterized by enhanced endothelial cell apoptosis. Progressive increase in serum sVCAM-1 levels is connected with disease activity aggravation and development of lupus microangiopathy.
Kluz
J
J
Department of Angiology, Arterial Hypertension and Diabetology, Wroclaw Medical University, Wroclaw, Poland. joannakluz@wp.pl
Kopeć
W
W
Jakobsche-Policht
U
U
Adamiec
R
R
D000293:Adolescent; D000328:Adult; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000097:blood*; D002452:Cell Count; D019040:E-Selectin / Q000097:blood; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D018189:Immunomagnetic Separation; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D008875:Middle Aged; D011044:Poland; D012720:Severity of Illness Index; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D014657:Vasculitis / Q000097:blood / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D055815:Young Adult
D015415:Biomarkers; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1