*Purpose: Chronic active antibody mediated rejection (CAAMR) induced by de novo donor specific antibodies (DSA) is the main cause of graft loss in the long-term. Currently, there is no effective treatment or predictive marker for CAAMR. Therefore, a reliable immunoresponse monitoring system to identify recipients who will develop CAAMR in the future is required to improve long-term allograft survival. In this study, we assessed whether a CFSE/MLR assay can diagnose CAAMR in kidney recipients with stable renal function.

*Methods: One hundred and six recipients, who received maintenance immunosuppressants of the calcineurin inhibitor, mycophenolate mofetil, and methylprednisolone were enrolled in this study. These recipients were divided into a DSA negative group (DSA-) and a DSA positive group (DSA+). We evaluated anti-donor and 3^rd party T cell responses using CFSE/MLR co-stained for CD4, CD8 or Foxp3.

*Results: In pathological analyses, no DSA- recipients experienced any incidents of rejection, while all DSA+ recipients experienced antibody-mediated rejection. We first performed CFSE/MLR using peripheral blood mononuclear cells (PBMC) in 24 kidney recipients (DSA-: n=19, DSA+: n=5). There was no difference in CD4+, CD8+ or regulatory T cell responses between the 2 groups (Fig1). Next, we isolated and assessed recipient T cells from PBMCs in 82 recipients (DSA-: n=74, DSA+: n=8). The anti-donor CD8+ T cell response was significantly higher in DSA+ patients than in DSA- patients. A CD4+ T cell hyper response, and regulatory T cell expansion against the donor tissue was also observed in DSA+ patients (Fig2). Although anti-3^rd party responses in DSA+ patients were also higher than those in DSA- patients, these differences were smaller than the anti-donor response.

*Conclusions: DSA+ kidney recipients have greater potential for immune response against the donor tissue. CFSE/MLR using isolated T cells is a useful immunoresponse monitoring system to predict CAAMR.

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