Pre-Transplant IgG Reactivity to Apoptotic Cells Correlates With Late Kidney Allograft Loss.

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Pre-existing antibodies in patient serum have long been associated with rejection and graft loss. While most studies have focused on characterizing HLA-specific abs, the contribution of non-HLA-reactive abs has been largely overlooked. Recently, we characterized polyreactive monoclonal abs derived from kidney graft recipients amidst rejection. These abs react to a broad range of common self-antigens as well as HLA for some of them. Their one constant was a capacity to bind to apoptotic cells (AC). Here we assessed the presence of such abs reactive to AC in pre-transplant patients and examined their contribution to graft outcomes. Pre-transplant sera from 300 patients along with sera from 20 healthy subjects were used in this study. IgG reactivity to HLA was assessed by Luminex. IgM and IgG reactivity to generic AC and complement activation was measured by flow cytometry. Overall, serum IgG but not IgM reactivity to AC was significantly higher in pre-transplant patients compared to healthy subjects. This reactivity was predominantly mediated by IgG1 and IgG3 with complement activating capacity. Pre-transplant IgG reactivity to AC significantly increased the risk of graft loss.Figure: No Caption available.The effect on graft loss was only apparent after approximately 1 year post-transplant. IgG reactivity to AC as an explanatory factor remained significantly associated to graft loss even when the reactivity to HLA and demographic variables were included. Based on our previous studies, we propose that this reactivity results in part from polyreactive abs. Overall, our findings support the view that abs cross-reactive to apoptotic cells contribute to “pre-sensitization” in patients on the kidney transplant waiting list.