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A Novel Immunoresponse Monitoring System to Predict Chronic Antibody- Mediated Rejection in Kidney Transplant Recipients

N. Iwahara1, K. Hotta1, D. Iwami1, Y. Takada1, H. Higuchi2, H. Sasaki2, T. Tanabe2, N. Shinohara1

1Hokkaido University, Sapporo, Japan, 2Sapporo City General Hospital, Sapporo, Japan

Meeting: 2020 American Transplant Congress

Abstract number: D-346

Keywords: Antibodies, Monitoring, T cells

Session Information

Session Name: Poster Session D: Lymphocyte Biology: Signaling, Co-Stimulation, Regulation

Session Type: Poster Session

Date: Saturday, May 30, 2020

Session Time: 3:15pm-4:00pm

 Presentation Time: 3:30pm-4:00pm

Location: Virtual

*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 3rd 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-3rd 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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To cite this abstract in AMA style:

Iwahara N, Hotta K, Iwami D, Takada Y, Higuchi H, Sasaki H, Tanabe T, Shinohara N. A Novel Immunoresponse Monitoring System to Predict Chronic Antibody- Mediated Rejection in Kidney Transplant Recipients [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/a-novel-immunoresponse-monitoring-system-to-predict-chronic-antibody-mediated-rejection-in-kidney-transplant-recipients/. Accessed May 11, 2025.

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