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An antibody-aptamer-hybrid lateral flow assay for detection of CXCL9 in antibody-mediated rejection after kidney transplantation.
Diagnostics 12:308 (2022)
Chronic antibody-mediated rejection (AMR) is a key limiting factor for the clinical outcome of a kidney transplantation (Ktx), where early diagnosis and therapeutic intervention is needed. This study describes the identification of the biomarker CXC-motif chemokine ligand (CXCL) 9 as an indicator for AMR and presents a new aptamer-antibody-hybrid lateral flow assay (hybrid-LFA) for detection in urine. Biomarker evaluation included two independent cohorts of kidney transplant recipients (KTRs) from a protocol biopsy program and used subgroup comparisons according to BANFF-classifications. Plasma, urine and biopsy lysate samples were analyzed with a Luminex-based multiplex assay. The CXCL9-specific hybrid-LFA was developed based upon a specific rat antibody immobilized on a nitrocellulose-membrane and the coupling of a CXCL9-binding aptamer to gold nanoparticles. LFA performance was assessed according to receiver operating characteristic (ROC) analysis. Among 15 high-scored biomarkers according to a neural network analysis, significantly higher levels of CXCL9 were found in plasma and urine and biopsy lysates of KTRs with biopsyproven AMR. The newly developed hybrid-LFA reached a sensitivity and specificity of 71% and an AUC of 0.79 for CXCL9. This point-of-care-test (POCT) improves early diagnosis-making in AMR after Ktx, especially in KTRs with undetermined status of donor-specific HLA-antibodies.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Antibody ; Antibody-mediated Rejection (amr) ; Aptamer ; Aptamer-antibody-hybrid Lateral Flow Assay (hybrid-lfa) ; Biomarkers ; Cxcl9 (mig) ; Neural Net Analysis; Donor-specific Antibody; Non-hla Antibodies; Urinary Cxcl9; Ifn-gamma; Activation; Chemokines; Classification; Expression; Challenges; Induction
ISSN (print) / ISBN
2075-4418
e-ISSN
2075-4418
Journal
Diagnostics
Quellenangaben
Volume: 12,
Issue: 2,
Article Number: 308
Publisher
MDPI
Publishing Place
St Alban-anlage 66, Ch-4052 Basel, Switzerland
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
CF Monoclonal Antibodies (CF-MAB)
Grants
Central Innovation Program for Small and Medium Entrepreneurs of the Federal Ministry for Economic Affairs and Energy Germany
German Center for Infection Research
Deutsche Forschungsgemeinschaft
German Center for Infection Research
Deutsche Forschungsgemeinschaft