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Seiler, L.K.* ; Phung, N.L.* ; Nikolin, C.* ; Immenschuh, S.* ; Erck, C.* ; Kaufeld, J.* ; Haller, H.* ; Falk, C.S.* ; Jonczyk, R.* ; Lindner, P.* ; Thoms, S.* ; Siegl, J.* ; Mayer, G.* ; Feederle, R. ; Blume, C.A.*

An antibody-aptamer-hybrid lateral flow assay for detection of CXCL9 in antibody-mediated rejection after kidney transplantation.

Diagnostics 12:308 (2022)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
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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
Language english
Publication Year 2022
HGF-reported in Year 2022
ISSN (print) / ISBN 2075-4418
e-ISSN 2075-4418
Journal Diagnostics
Quellenangaben Volume: 12, Issue: 2, Pages: , Article Number: 308 Supplement: ,
Publisher MDPI
Publishing Place St Alban-anlage 66, Ch-4052 Basel, Switzerland
Reviewing status Peer reviewed
Institute(s) CF Monoclonal Antibodies (CF-MAB)
POF-Topic(s) 30201 - Metabolic Health
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-502210-001
A-631900-001
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
DOI 10.3390/diagnostics12020308
WOS ID WOS:000763949100001
Scopus ID 85124327642
PubMed ID 35204399
Erfassungsdatum 2022-06-24
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