Non-HLA antibodies reactive against endothelial cells may cause early loss of renal allografts

Abstract

There is increasing evidence that antibodies driven against non-HLA antigens of endothelial cells (AECA) are associated to the transplant rejection. Purpose: 1. To assess the presence of AECA in eluates in kidneys lost from non-HLA antibodies mediated rejection; 2. To verify the possibility if those AECA could be detected in the pre-transplant and pre-rejection sera; 3. To verify the potential inhibitory activity of the IVIg on such antibodies. Methods: Platelet-absorbed sera and eluates from 12 renal allografts were tested by flow cytometry against the endothelial/epithelial hybridoma cell line EAHy.926. Positive eluates were then tested with or without the addition of an intravenous polyvalent immunoglobulin preparation (IVIg). Results: The absence of anti-HLA antibodies against the donor was ascertained at the transplant, at rejection, and before and after the transplantectomy by negativity of the cross matches performed using the most sensitive techniques. Antibodies from nine eluates bound to EAHy.926. In seven out of nine cases, the C4d deposition was not found. These AECA were not detected in the pre-transplant sera. However, 2 out of 4 pre-rejection sera were positive for AECA, and one showed a borderline reactivity. In 9 cases, the addition of IVIg led to a strong decrease of AECA the binding. Conclusion: These data showed that AECA may be associated to humoral rejection. The detection of such antibodies in pre-rejection sera opens the possibility of a new immune monitoring. The use of IVIg to block the binding of such antibodies to the target cells can thus offer a potential therapy for humoral rejections.