340.11: Flow Cytometric Pattern of Gamma Delta TCR Expression Identifies Outcomes in Kidney Transplantation

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Purpose: The main challenge with kidney transplantation is the possibility of rejection, classified into two types, antibody-mediated rejection (ABMR) and T cell-mediated rejection (TCMR). The role of γδ T cells in renal transplantation outcomes is yet to be clarified. Methods: We studied the immune repertoire in the peripheral blood of 25 unique kidney transplant recipients with both TCMR and ABMR and stable (STA) allografts confirmed by renal allograft biopsies. Using RNASeq data on these samples we conducted statistical computational approaches to compute the immunoglobulin and T-cell receptor (TCR) reads from RNA sequencing data. A TCR-based multi-parameter flow cytometry protocol was designed to detect γδ T cells in an independent validation set of AR samples to evaluate the ability to differentiate TCMR from ABMR by a blood sample cytometric analysis, paired with the allograft biopsy. Results: We found that the ratio of all α, β TCR by γ, δ TCR is associated with the transplant outcomes, with the ratio being greater in ABMR and TCMR than in STA. In addition, this ratio is associated with several genes showing enrichment in the organ rejection pathways and classifying the patients into their clinical outcomes. γδ T cell lineage is enriched in STA than rejections. Comparing both the rejections, the γδ T cell lineage is significantly (p=0.0131) lower in ABMR. Conclusions: The TCR panel, based on the γδT cell antibody by flow cytometry, could be advantageous for the rapid identification of the sub-type of kidney rejection by blood sampling, without the need of an invasive biopsy.

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