A new lateral flow assay to detect sIL-2R during T-cell mediated rejection after kidney transplantation

Research output: Contribution to journalArticleResearchpeer review

Authors

  • Lisa K. Seiler
  • Rebecca Jonczyk
  • Patrick Lindner
  • Ncog Linh Phung
  • Christine S. Falk
  • Jessica Kaufeld
  • Wilfried Gwinner
  • Irina Scheffner
  • Stephan Immenschuh
  • Cornelia Blume

Research Organisations

External Research Organisations

  • Hannover Medical School (MHH)
View graph of relations

Details

Original languageEnglish
Pages (from-to)5369-5379
Number of pages11
JournalANALYST
Volume146
Issue number17
Early online date2 Aug 2021
Publication statusPublished - 7 Sept 2021

Abstract

Kidney is the most frequently transplanted among all solid organs worldwide. Kidney transplant recipients (KTRs) undergo regular follow-up examinations for the early detection of acute rejections. The gold standard for proving a T-cell mediated rejection (TCMR) is a biopsy of the renal graft often occurring as indication biopsy, in parallel to an increased serum creatinine that may indicate deterioration of renal transplant function. The goal of the current work was to establish a lateral flow assay (LFA) for diagnosing acute TCMR to avoid harmful, invasive biopsies. Soluble interleukin-2 (IL-2) receptor (sIl-2R) is a potential biomarker representing the α-subunit of the IL-2 receptor produced by activated T-cells, e.g., after allogen contact. To explore the diagnostic potential of sIL-2R as a biomarker for TCMR and borderline TCMR, plasma and urine samples were collected from three independent KTR cohorts with various distinct histopathological diagnostic findings according to BANFF (containing 112 rsp. 71 rsp. 61 KTRs). Samples were analyzed by a Luminex-based multiplex technique and cut off-ranges were determined. An LFA was established with two specific sIL-2R-antibodies immobilized on a nitrocellulose membrane. A significant association between TCMR, borderline TCMR and sIL-2R in plasma and between TCMR and sIL-2R in urine of KTRs was confirmed using the Mann-Whitney U test. The LFA was tested with sIL-2R-spiked buffer samples establishing a detection limit of 25 pM. The performance of the new LFA was confirmed by analyzing urine samples of the 2nd and 3rd patient cohort with 35 KTRs with biopsy proven TCMRs, 3 KTRs diagnosed with borderline TCMR, 1 mixed AMR/TCMR rsp. AMR/borderline TCMR and 13 control patients with a rejection-free kidney graft proven by protocol biopsies. The new point-of-care assay showed a specificity of 84.6% and sensitivity of 87.5%, and a superior estimated glomerular filtration rate (eGFR) at the time point of biopsy (specificity 30.8%, sensitivity 85%).

ASJC Scopus subject areas

Cite this

A new lateral flow assay to detect sIL-2R during T-cell mediated rejection after kidney transplantation. / Seiler, Lisa K.; Jonczyk, Rebecca; Lindner, Patrick et al.
In: ANALYST, Vol. 146, No. 17, 07.09.2021, p. 5369-5379.

Research output: Contribution to journalArticleResearchpeer review

Seiler, LK, Jonczyk, R, Lindner, P, Phung, NL, Falk, CS, Kaufeld, J, Gwinner, W, Scheffner, I, Immenschuh, S & Blume, C 2021, 'A new lateral flow assay to detect sIL-2R during T-cell mediated rejection after kidney transplantation', ANALYST, vol. 146, no. 17, pp. 5369-5379. https://doi.org/10.1039/d1an01001h
Seiler, L. K., Jonczyk, R., Lindner, P., Phung, N. L., Falk, C. S., Kaufeld, J., Gwinner, W., Scheffner, I., Immenschuh, S., & Blume, C. (2021). A new lateral flow assay to detect sIL-2R during T-cell mediated rejection after kidney transplantation. ANALYST, 146(17), 5369-5379. https://doi.org/10.1039/d1an01001h
Seiler LK, Jonczyk R, Lindner P, Phung NL, Falk CS, Kaufeld J et al. A new lateral flow assay to detect sIL-2R during T-cell mediated rejection after kidney transplantation. ANALYST. 2021 Sept 7;146(17):5369-5379. Epub 2021 Aug 2. doi: 10.1039/d1an01001h
Seiler, Lisa K. ; Jonczyk, Rebecca ; Lindner, Patrick et al. / A new lateral flow assay to detect sIL-2R during T-cell mediated rejection after kidney transplantation. In: ANALYST. 2021 ; Vol. 146, No. 17. pp. 5369-5379.
Download
@article{13cc166473b3465bb33eb52488e75bda,
title = "A new lateral flow assay to detect sIL-2R during T-cell mediated rejection after kidney transplantation",
abstract = "Kidney is the most frequently transplanted among all solid organs worldwide. Kidney transplant recipients (KTRs) undergo regular follow-up examinations for the early detection of acute rejections. The gold standard for proving a T-cell mediated rejection (TCMR) is a biopsy of the renal graft often occurring as indication biopsy, in parallel to an increased serum creatinine that may indicate deterioration of renal transplant function. The goal of the current work was to establish a lateral flow assay (LFA) for diagnosing acute TCMR to avoid harmful, invasive biopsies. Soluble interleukin-2 (IL-2) receptor (sIl-2R) is a potential biomarker representing the α-subunit of the IL-2 receptor produced by activated T-cells, e.g., after allogen contact. To explore the diagnostic potential of sIL-2R as a biomarker for TCMR and borderline TCMR, plasma and urine samples were collected from three independent KTR cohorts with various distinct histopathological diagnostic findings according to BANFF (containing 112 rsp. 71 rsp. 61 KTRs). Samples were analyzed by a Luminex-based multiplex technique and cut off-ranges were determined. An LFA was established with two specific sIL-2R-antibodies immobilized on a nitrocellulose membrane. A significant association between TCMR, borderline TCMR and sIL-2R in plasma and between TCMR and sIL-2R in urine of KTRs was confirmed using the Mann-Whitney U test. The LFA was tested with sIL-2R-spiked buffer samples establishing a detection limit of 25 pM. The performance of the new LFA was confirmed by analyzing urine samples of the 2nd and 3rd patient cohort with 35 KTRs with biopsy proven TCMRs, 3 KTRs diagnosed with borderline TCMR, 1 mixed AMR/TCMR rsp. AMR/borderline TCMR and 13 control patients with a rejection-free kidney graft proven by protocol biopsies. The new point-of-care assay showed a specificity of 84.6% and sensitivity of 87.5%, and a superior estimated glomerular filtration rate (eGFR) at the time point of biopsy (specificity 30.8%, sensitivity 85%).",
author = "Seiler, {Lisa K.} and Rebecca Jonczyk and Patrick Lindner and Phung, {Ncog Linh} and Falk, {Christine S.} and Jessica Kaufeld and Wilfried Gwinner and Irina Scheffner and Stephan Immenschuh and Cornelia Blume",
note = "Funding Information: The work addressing the 1st cohort was funded by the start-up project SU02 and the Core Facility Diagnostic Centre of the IFB-Tx, ref. no. 01EO0802, the DFG SFB738-B8 projects and the DZIF TTU-IICH07.801. The continued biomarker evaluation was funded by the European Regional Development Fund (ERDF), subproject A (ref. no. 85006385). All further parts of this work have been carried out within the framework of the SMART-BIOTECS alliance between the Technical University Braunschweig and the Leibniz University Hannover. This initiative is supported by the Ministry of Science and Culture (MWK) of Lower Saxony, Germany. We further thank Prof. Dr Stephan Immenschuh for his critical proofreading of the manuscript.",
year = "2021",
month = sep,
day = "7",
doi = "10.1039/d1an01001h",
language = "English",
volume = "146",
pages = "5369--5379",
journal = "ANALYST",
issn = "0003-2654",
publisher = "Royal Society of Chemistry",
number = "17",

}

Download

TY - JOUR

T1 - A new lateral flow assay to detect sIL-2R during T-cell mediated rejection after kidney transplantation

AU - Seiler, Lisa K.

AU - Jonczyk, Rebecca

AU - Lindner, Patrick

AU - Phung, Ncog Linh

AU - Falk, Christine S.

AU - Kaufeld, Jessica

AU - Gwinner, Wilfried

AU - Scheffner, Irina

AU - Immenschuh, Stephan

AU - Blume, Cornelia

N1 - Funding Information: The work addressing the 1st cohort was funded by the start-up project SU02 and the Core Facility Diagnostic Centre of the IFB-Tx, ref. no. 01EO0802, the DFG SFB738-B8 projects and the DZIF TTU-IICH07.801. The continued biomarker evaluation was funded by the European Regional Development Fund (ERDF), subproject A (ref. no. 85006385). All further parts of this work have been carried out within the framework of the SMART-BIOTECS alliance between the Technical University Braunschweig and the Leibniz University Hannover. This initiative is supported by the Ministry of Science and Culture (MWK) of Lower Saxony, Germany. We further thank Prof. Dr Stephan Immenschuh for his critical proofreading of the manuscript.

PY - 2021/9/7

Y1 - 2021/9/7

N2 - Kidney is the most frequently transplanted among all solid organs worldwide. Kidney transplant recipients (KTRs) undergo regular follow-up examinations for the early detection of acute rejections. The gold standard for proving a T-cell mediated rejection (TCMR) is a biopsy of the renal graft often occurring as indication biopsy, in parallel to an increased serum creatinine that may indicate deterioration of renal transplant function. The goal of the current work was to establish a lateral flow assay (LFA) for diagnosing acute TCMR to avoid harmful, invasive biopsies. Soluble interleukin-2 (IL-2) receptor (sIl-2R) is a potential biomarker representing the α-subunit of the IL-2 receptor produced by activated T-cells, e.g., after allogen contact. To explore the diagnostic potential of sIL-2R as a biomarker for TCMR and borderline TCMR, plasma and urine samples were collected from three independent KTR cohorts with various distinct histopathological diagnostic findings according to BANFF (containing 112 rsp. 71 rsp. 61 KTRs). Samples were analyzed by a Luminex-based multiplex technique and cut off-ranges were determined. An LFA was established with two specific sIL-2R-antibodies immobilized on a nitrocellulose membrane. A significant association between TCMR, borderline TCMR and sIL-2R in plasma and between TCMR and sIL-2R in urine of KTRs was confirmed using the Mann-Whitney U test. The LFA was tested with sIL-2R-spiked buffer samples establishing a detection limit of 25 pM. The performance of the new LFA was confirmed by analyzing urine samples of the 2nd and 3rd patient cohort with 35 KTRs with biopsy proven TCMRs, 3 KTRs diagnosed with borderline TCMR, 1 mixed AMR/TCMR rsp. AMR/borderline TCMR and 13 control patients with a rejection-free kidney graft proven by protocol biopsies. The new point-of-care assay showed a specificity of 84.6% and sensitivity of 87.5%, and a superior estimated glomerular filtration rate (eGFR) at the time point of biopsy (specificity 30.8%, sensitivity 85%).

AB - Kidney is the most frequently transplanted among all solid organs worldwide. Kidney transplant recipients (KTRs) undergo regular follow-up examinations for the early detection of acute rejections. The gold standard for proving a T-cell mediated rejection (TCMR) is a biopsy of the renal graft often occurring as indication biopsy, in parallel to an increased serum creatinine that may indicate deterioration of renal transplant function. The goal of the current work was to establish a lateral flow assay (LFA) for diagnosing acute TCMR to avoid harmful, invasive biopsies. Soluble interleukin-2 (IL-2) receptor (sIl-2R) is a potential biomarker representing the α-subunit of the IL-2 receptor produced by activated T-cells, e.g., after allogen contact. To explore the diagnostic potential of sIL-2R as a biomarker for TCMR and borderline TCMR, plasma and urine samples were collected from three independent KTR cohorts with various distinct histopathological diagnostic findings according to BANFF (containing 112 rsp. 71 rsp. 61 KTRs). Samples were analyzed by a Luminex-based multiplex technique and cut off-ranges were determined. An LFA was established with two specific sIL-2R-antibodies immobilized on a nitrocellulose membrane. A significant association between TCMR, borderline TCMR and sIL-2R in plasma and between TCMR and sIL-2R in urine of KTRs was confirmed using the Mann-Whitney U test. The LFA was tested with sIL-2R-spiked buffer samples establishing a detection limit of 25 pM. The performance of the new LFA was confirmed by analyzing urine samples of the 2nd and 3rd patient cohort with 35 KTRs with biopsy proven TCMRs, 3 KTRs diagnosed with borderline TCMR, 1 mixed AMR/TCMR rsp. AMR/borderline TCMR and 13 control patients with a rejection-free kidney graft proven by protocol biopsies. The new point-of-care assay showed a specificity of 84.6% and sensitivity of 87.5%, and a superior estimated glomerular filtration rate (eGFR) at the time point of biopsy (specificity 30.8%, sensitivity 85%).

UR - http://www.scopus.com/inward/record.url?scp=85113299598&partnerID=8YFLogxK

U2 - 10.1039/d1an01001h

DO - 10.1039/d1an01001h

M3 - Article

C2 - 34337623

AN - SCOPUS:85113299598

VL - 146

SP - 5369

EP - 5379

JO - ANALYST

JF - ANALYST

SN - 0003-2654

IS - 17

ER -

By the same author(s)