Inhibition of prostacyclin release by endothelial binding anticardiolipin antibodies in thrombosis-prone patients with systemic lupus erythematosus and the antiphospholipid syndrome.
IgG from 18 patients with SLE, eight with the primary antiphospholipid syndrome and 19 controls was examined for its effect on thrombin-induced prostacyclin (PGI2) release from human umbilical vein endothelial cells in relation to both the titre of anticardiolipin (ACA) and antiendothelial activity (AEA) and clinical thrombotic events. Although no significant inhibition of PGI2 release was found overall, examination of subgroups revealed that IgG from patients with ACA produced significant inhibition of PGI2 release (mean stimulation index IgGM, 0.74 +/- 0.12, P = 0.02) when compared with patients without ACA (1.18 +/- 0.12). Further analysis revealed a significant positive correlation between ACA and AEA (r = 0.52, P = 0.006) in the total patient group which was reflected in significant negative correlations between inhibition of PGI2 release and increasing titre of both ACA (r = -0.42, P = 0.032) and AEA (r = -0.57, P = 0.002). However, only increasing titre of AEA showed a significant negative correlation with inhibition of PGI2 release when patients with (r = -0.74, P = 0.0005) and without (r = 0.23, N.S.) thromboses were compared. The titre of ACA failed to show any significant correlation with inhibition of PGI2 release in either patients with (r = -0.42, N.S.) or without (r = -0.16, N.S.) thromboses. These findings suggest that previous, sometimes conflicting, reports of an association between inhibition of PGI2 release and ACA may be explained by the co-incidence of AEA with ACA.
Lindsey
N J
NJ
University Department of Medicine, Northern General Hospital, Sheffield.
Henderson
F I
FI
Malia
R
R
Milford-Ward
M A
MA
Greaves
M
M
Hughes
P
P
D000328:Adult; D017153:Antibodies, Anticardiolipin / Q000378:metabolism*; D016736:Antiphospholipid Syndrome / Q000150:complications / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D011464:Epoprostenol / Q000378:metabolism*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000502:physiology; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000276:immunology / Q000378:metabolism*; D008297:Male; D012307:Risk Factors; D013927:Thrombosis / Q000453:epidemiology* / Q000378:metabolism*
D017153:Antibodies, Anticardiolipin; D007074:Immunoglobulin G; D011464:Epoprostenol