AUTHOR=Lammerts Rosa G. M. , Born Jacob van den , Huberts-Kregel Magdalena , Gomes-Neto Antonio W. , Daha Mohammed R. , Hepkema Bouke G. , Sanders Jan-Stephan , Pol Robert A. , Diepstra Arjan , Berger Stefan P. 

TITLE=Renal Endothelial Cytotoxicity Assay to Diagnose and Monitor Renal Transplant Recipients for Anti-Endothelial Antibodies

JOURNAL=Frontiers in Immunology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.845187

DOI=10.3389/fimmu.2022.845187

ISSN=1664-3224

ABSTRACT=Tissue specific non-HLA antigens can play crucial roles in allograft immunity and have been shown to trigger humoral responses leading to rejection of HLA-matched kidney allografts. Interest in the role of endothelial specific antigens has grown over the past years, and several case reports have been described in which antibodies reacting with endothelial cells (ECs) are associated with rejection. Such antibodies escape the detection in conventional crossmatch tests, as they do not react with lymphocytes. However, due to the heterogeneity of endothelial cells from different vascular beds, it remains difficult to draw organ specific conclusions from studies describing endothelial cross match assays. We present a case of a 69 year old male patient, whose kidney allograft was rejected hyperacute, in spite of the absence of pre-transplant HLA-specific antibodies. In order to place findings from previous studies in a kidney related context, we performed cross match assays with primary renal endothelial cells. The patient’s serum was reactive with primary renal ECs, demonstrated by antibody binding and complement-dependent-cytotoxicity. Antibodies from this patient did not react with lymphocytes, nor were HLA donor-specific-antibodies (DSAs) found. Two years later the patient successfully received a second kidney transplant after treatment with rituximab and plasmapheresis before and after transplantation. We demonstrated that removal of antibodies against non-HLA ECs specific molecules can be monitored using a primary renal EC crossmatch test, possibly contributing to a successful transplantation outcome.