Enhanced Binding of Antiendothelial Cell Antibody by IL-1alpha in Systemic Lupus Erythematosus

Hong, Yeon Sik; Kim, Wan Uk; Min, Jun Ki; Park, Sung Hwan; Lee, Sang Heon; Cho, Chul Soo; Kim, Ho Youn

Abstract

Systemic lupus erythematosus(SLE) is a multiorgan disease which is associated with the occurrence of immune vascular damage. Antiendothelial cell antibodies(aECA) have been demonstrated in patients with SLE, and their presence could be related to vascular injury. Endothelial cell(EC) in vasculitic lesions of patients with SLE show evidence of activation. In vitro treatment of EC with cytokines can produce a pattern of activation such as the increased expression of surface molecules. Activation of EC was shown to influence the interaction between aECA and endothelial surface. The authors, therefore, examined the prevalence of IgG aECA and investigated the association of aECA with clinical findings and anticardiolipin antibodies(aCL). We also investigated the role of cytokine in binding of IgG-aECA to EC in patients with SLE. Sera from 92 patients with SLE and 20 healthy controls were assayed for IgG- aECA by cellular ELISA method using cultured human umbilical vein endothelial cell(HUVEC) and IgG-aCL by ELISA method, and We also examined the binding of IgG-aECA to EC activated with IL-1 or TNF-a< in sera from 60 patients with SLE. IgG-aECA was detected in the serum of 31 out of 92 patients(33.7%). The mean serum titers of IgG-aECA were significantly higher in SLE than in healthy controls(19.38 U/ml vs 8.79 U/ml, P<0.05). There was no correlation between serum titers of IgG-aECA and IgG-aCL(r=-0.0265). The mean serum titers of IgG-aECA in patients with digital vasculitis or Raynaud' s phenomenon were significantly increased in comparison with patients without these manifestations (35. 28 U/ml vs 18. 16 U/ml, P<0.05, 27.18 U/ml vs 15. 24 U/ml, P<0.05 respectively). The mean serum titers of IgG-aECA in 60 patients were significantly increased(P<0.0001) following the stimulation with IL-la as compared with unstimulated EC, but those of IgG-aECA were not increased following the stimulation with TNF-a<. The IgG-aECA binding reactivity to IL-la stimulated EC was significantly higher in patients with digital vasculitis, Raynaud s phenomenon, renal disorder, thrombosis, neuropsychiatric manifestation and avascular necrosis as compared with unstimulated EC. IgG-aECA was detected in 28 of the 60 patients(46. 7%). Its frequency was increased following the stimulation with IL-1<(68. 3%), but there was no significant difference in frequency following the stimulation with TNF-a<(48.3%). These data suggest that presence of IgG-aECA and enhanced binding of IgG- aECA to EC induced by IL-la< can play an important role in the occurrence of clinical manifestations associated with vascular damage in SLE.