Artikel
IgG from patients with systemic lupus erythematosus and systemic sclerosis have an influence on coagulation factors in human cerebral microvascular endothelial cells in-vitro
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Veröffentlicht: | 9. September 2020 |
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Gliederung
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Introduction: Patients with systemic lupus erythematosus (SLE) or systemic sclerosis (SSc) can show various symptoms of the central nervous system. Both disease entities are characterised by distinct autoantibodies and endothelial damage, especially in microvessels. Anti-endothelial cell autoantibodies (AECA) can be detected in SLE and SSc and appear to play a critical role in the disease-associated vasculopathy. So far, there is no evidence that AECA bind to endothelial cells from the brain microvasculature (hBMEC), and it is not clear whether they exert a pathologic effect on this special type of endothelial cell.
We investigated, whether autoantibodies against hBMEC are detectable in SLE and SSc patients and if they have an influence on EC activation by inducing adhesion molecules, and on haemostasis by inducing factors of the clotting cascade.
Methods: 26 SLE patients and 29 SSc patients were tested for autoantibodies against human cerebral microvascular endothelia cells (hCMEC/D3) via flow cytometry. IgG antibodies were purified from sera with HiTrap Protein G HP antibody purification columns. The expression of selected surface proteins was measured using flow cytometry: ICAM-1, VCAM-1, MHC class I and II, tissue factor, von-Willebrand-Factor, E-Selectin, P-Selectin, thrombomodulin, CD73 and t-PA, before and after three- and 24-hour incubation with IgG-fractions, respectively. IgG fractions of 12 SLE, 13 SSc patients and 13 healthy control persons (HC) were tested.
Results: Autoantibodies against hCMEC/D3 were found in 21/26 of SLE (81%) and in 19/29 SSc patients (66%) but not in HC. After three hours of incubation of hCMEC/D3 with IgG-fractions, a significant upregulation of tissue factor by SSc-IgG (6.7% ± 5.2%) compared to HC-IgG (1.1% ± 2.8%, p < 0.01) and to SLE-IgG (1.6% ± 3.9%, p < 0.05), was detectable.
There was no significant correlation between changes in surface protein expression and detection of ANA, nor of anti-hCMEC/D3 antibodies. There was no change in expression of the other investigated proteins.
Conclusion: SLE and SSc patients show autoantibodies against hBMEC. IgG fractions of patients with SSc induce an upregulation of tissue factor on the cell surface of hCMEC/D3, which may be an indicator for a direct pathogenic effect of AECA on hBMEC and might have an influence on haemostasis.
Disclosures: No disclosures
References
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