Activation of the immune system and coronary artery disease: the role of anti-endothelial cell antibodies

On the basis of the role of immune-mediated inflammation in atherosclerosis we investigated, (1) the prevalence of anti-endothelial cell antibodies (A ECA) in ischaemic heart disease IHD); (2) if beta2-glycoprotein I (beta2-GP I) was the target antigen of AECA, (3) the relationship between AECA. tissu e factor (TF) and tissue factor pathway inhibitor (TFPI). In 93 consecutive IHD patients undergoing percutaneous transluminal coronary angioplasty (PT CA) and 105 controls AECA were detected by ELISA on human umbilical vein en dothelial cells (HUVEC). AECA positive sera were evaluated for anti-beta2-G PI antibodies by ELISA. TF and TFPI plasma levels were assessed by ELISA. T welve of 93 (12.9%) IHD patients and only one of 105 controls (0.95%) were AECA positive. The prevalence of AECA was higher in unstable angina (UA) th an in effort angina (EA) (P = 0.01). Three of 12 AECA positive sera resulte d positive for anti-beta2-GPI and showed a marked decrease in EC-binding wh en tested on HUVEC cultured in serum-free medium. The binding was restored by the addition of beta2-GPI. TF and TFPI levels were similar in AECA posit ive and AECA negative patients. The rate of angiographically documented cli nical recurrences was 66.7% in the AECA positive and 14.8% in the AECA nega tive group (P = 0.0004) with a significant relationship between restenosis and AECA (P < 0.0001), unchanged by the inclusion of cardiovascular risk fa ctors in the regression model. Our results suggest a 'role' for AECA in the immune-mediated inflammation in UA <beta>2-GPI is not the only AECA target antigen. AECA are not responsible for high TF and TFPI levels. The high ra te of clinical recurrences after PTCA. confirmed by angiography. in AECA po sitive patients is in line with such a role and suggests further large-scal e 'ad hoc' studies. (C) 2001 Elsevier Science Ireland Ltd. All rights reser ved.