Date: Monday, June 3, 2019
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall C & D
*Purpose: Anti-HLA antibodies, both pre-formed and de novo are associated with worse graft survival. Complement activation is an important mechanism of antibody mediated immunological injury. We hypothesised that anti-HLA antibodies may differentially induce expression of complement regulatory proteins thus resulting in differential injury.
*Methods: Human primary renal glomerular endothelial cells (HRGEC) were HLA typed. Cells at passage 3-6, were stimulated with Gamma Interferon for 48hours. Cells were then exposed to sera with cell HLA specific anti-HLA class I, Class II and Class I+II antibodies in separate experiments. Sera with no antibodies acted as a negative control. Expression of mRNA for CD46, CD55, and CD59 were studied by qPCR for all these 4 conditions. Cell lysates collected for Western blot and Flow cytometry were also studied for all the 4 conditions.
*Results: mRNA isolated from endothelial cells, was quantified for CD46, CD55 and CD59 expression by qPCR and there was no difference in expression levels after 48hours under 4 conditions. There was also no difference in surface expression of CD46, CD55 and CD59 by western blot. In the Figure 1a overlay graph CD46 expression is not altered under 3 different conditions compared to negative control. Similar findings are presented for CD55 and CD59 expression in Figures 1b and 1c respectively.
*Conclusions: In these experiments, we clearly show that CD46, CD55 and CD59 expression on renal glomerular endothelial cells do not change in the presence of anti-HLA antibodies. Different susceptibility of anti HLA class1 and class II antibodies are not explained by this mechanism. Upregulation of these underutilized targets may confer additional endothelial protection in the presence of antibodies, especially if the immune-mediated damage is related to complement activation.
To cite this abstract in AMA style:Babu A, Pham T, Hamdorf M, Jucaud V, Everly M, Daga S, Mitchell D. Endothelial Cells Do Not Regulate Expression of CD46, CD55 and CD59 in the Presence of Anti-HLA Class I and 11 Antibodies [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/endothelial-cells-do-not-regulate-expression-of-cd46-cd55-and-cd59-in-the-presence-of-anti-hla-class-i-and-11-antibodies/. Accessed April 8, 2020.
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