OR23 Antibodies to MICA, AT1R and endothelial cells occur independently in transplant patients and in sera

Abstract

We sought to understand the incidence of antibodies (Ab) to HLA, MICA, AT1R or endothelial cells (EC) in pre- and post-transplant patients, and whether such Ab present concurrently in patients and in single serum samples. We retrospectively analyzed clinical results from pre- and post-transplant patients tested for AT1R, MICA, HLA, and EC Ab, and evaluated single serum samples tested for multiple types of Ab to determine whether these Ab occur together. AT1R Ab were measured by quantitative ELISA; HLA and MICA Ab were detected by Luminex single antigen; Ab to EC were detected in a flow cytometric crossmatch against mature primary aortic EC (ECXM). In transplant patients, the overall incidence of patients with Ab to EC was 43.2%, MICA Ab were seen in 9.9%, and 57.1% had AT1R Ab in at least one test. Regraft patients were more likely to exhibit EC or MICA Ab, particularly those with a deceased donor transplant compared with a living donor. HLA Ab were also correlated with anti-EC and MICA Ab. 78 serum samples were tested for all 3 non-HLA Ab. 26.9% of sera were negative for all three tests, while 1.3% were positive for all. There was no correlation between Ab to MICA and anti-EC Ab tested in the same serum. However, a majority of samples positive for ECXM also had AT1R Ab. AT1R Ab were significantly higher in sera that were positive for ECXM (28.8U/mL in ECXM+ vs. 19.4U/mL in ECXM-); however, 21.9% of samples without AT1R Ab were positive in ECXM, while 19% of samples negative for ECXM had very strong (>40 U/mL) AT1R Ab. Finally, in patients who had both ECXM testing and XM-ONE against potential donors, there was no apparent correlation between Ab to mature EC and donor specific endothelial precursors. HLA sensitized patients and regraft patients were more likely to have either EC or MICA Ab. The incidence of AT1R Ab was high; however, testing tended focus on high risk patients and may not reflect true incidence in the general transplant population. Serum with high AT1R Ab also tended to be positive for ECXM, but there were cases with strong AT1R Ab but negative ECXM. These results suggest that Ab to MICA, AT1R and EC are manifestations of different immune responses and a panel of non-HLA Ab testing is informative to identify different types of non-HLA Ab that may be detrimental graft survival.