Session Name: Biomarker Discovery and Immune Modulation
Session Date & Time: None. Available on demand.
*Purpose: Despite tremendous improvements in quality and tolerability of immunosuppressive medications after successful kidney transplantation, numerous kidney grafts undergo acute and chronic rejections with following function loss. To detect and treat rejections as early as possible, follow-up examinations are mandatory and here the gold standard is represented by kidney graft biopsies. However, these sensitive examinations are not harmless and involve risks like bleeding and infections. Therefore, an easy-to-use lateral flow assay (LFA) for kidney transplant recipients (KTRs) was developed in the here presented project.
*Methods: CXCL9 in urine and plasma samples from kidney graft recipients were analyzed by multiplex-ELISA. This messenger protein out of a group of homologous chemokines is an early signal produced within rejection episodes, e.g. by human macrophages presenting allogen or by the activated renal graft endothelium itself. Based on the identified range of relevant CXCL9 concentrations in urine and plasma samples, a LFA was developed. Initially, spiked buffer was used and the lateral flow assay was established. Following, samples from patients with kidney rejections as well as samples of unsuspicious patients as negative controls were applied onto the optimized LFA.
*Results: An association between acute T cell mediated and antibody mediated chronic rejections and CXCL9 in plasma and urine could be determined (rejectors (N=48)/plasma: 720.96 pg/mL ± 677.96 pg/mL versus controls (N=42), 213.60 pg/mL plusmn 160 pg/mL, p<0.0001; rejectors (N=47)/urine: 127.56 pg/mL plusmn 143.62 pg/mL versus controls (N=31), 39.61 pg/mL plusmn 29.86 pg/mL, p<0.001 Mann Whitney U test). In the lateral flow assay using spiked buffer a limit of detection was realizied. Samples from patients with a biopsy proven acute or chronic kidney rejection as well as samples of unsuspicious patients were already successfully applied with a reasonable sensitivity and specificity values >70&percnt.
*Conclusions: In this study, the value of CXCL9 detection in plasma and urine of patients with TCMR and AMR after kidney transplantation was confirmed. Furthermore, a lateral flow assay as point of care test for CXCL9 was developed.
To cite this abstract in AMA style:Seiler LK, Jonczyk R, Lindner P, Phung L, Falk C, Blume C. Development of a Lateral Flow Assay Detecting CXCL9 within Antibody Mediated and Acute T Cell Mediated Rejections After Kidney Transplantation [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/development-of-a-lateral-flow-assay-detecting-cxcl9-within-antibody-mediated-and-acute-t-cell-mediated-rejections-after-kidney-transplantation/. Accessed June 13, 2021.
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