Rejection of Human Kidney Allografts According to BANFF Classification Is Associated with a Chemokine-Enriched Protein Microenvironment in Biopsy Tssue.
1Institute of Transplant Immunology, IFB-Tx, Hannover Medical School, Hannover, Germany
2Department of Abdominal, Visceral and Transplantation Surgery, Hannover Medical School, Hannover, Germany
3Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany
4Institute of Pathology, Hannover Medical School, Hannover, Germany
5Institute for Technical Chemistry, Leibniz University, Hannover, Germany
Meeting: 2017 American Transplant Congress
Abstract number: D34
Keywords: Biopsy, Kidney transplantation, Monitoring, Rejection
Session Information
Session Name: Poster Session D: Diagnostics/Biomarkers Session II
Session Type: Poster Session
Date: Tuesday, May 2, 2017
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall D1
Background: Expression profiling efforts of biopsy tissue after kidney transplantation indicate that rejection can be defined by distinct signatures. Based on pathological evaluation (BANFF) as T cell-mediated (TCMR), AMR or borderline rejection, we hypothesized that the presence of immune cells within the graft would be associated with a distinct cytokine milieu. Therefore, we determined the protein microenvironment in kidney biopsies and correlated cytokines and chemokines with pathological staging.
Methods: From our protocol biopsy program, 37 snap-frozen kidney biopsies were obtained from transplant recipients ranging from 2 months to 20 years after Tx with ethical approval, informed consent. Protein lysates of capsule, cortical and medullary biopsy regions were analyzed for 50 cytokines, chemokines using multiplex protein arrays. Histopathological evaluation of was performed according to BANF criteria (14 unsuspicious, 4 TCMR, 5 borderline, 14 AMR).
Results: The protein microenvironment differed significantly between caspular, cortical and medullary kidney regions even in unsuspicious biopsies. In contrast, pro-inflammatory cytokines like IL-6, IL-8 (CXCL8), IFN-g, TNF-a were very low and did not differ between unsuspicious and rejection biopsies. However, significantly higher concentrations of chemokines like CXCL9,10, CCL5, growth factors, i.e. HGF were detected in cortical and medullary biopsy regions of the rejection group (all p<0.01).
Conclusion: The protein microenvironment of kidney biopsies histologically classified as rejection differs significantly from unsuspicious renal tissue with respect to the chemokine but not the cytokine milieu. Thus, certain chemokines like CXCL9, 10 confirm their qualification as biomarker candidates also at the protein level while typical T cell-derived cytokines seem to perform rather poorly as biomarkers.
CITATION INFORMATION: Falk C, Daemen K, Keil J, Lehner F, Haller H, Schmitz J, Bräsen J.-H, Blume C. Rejection of Human Kidney Allografts According to BANFF Classification Is Associated with a Chemokine-Enriched Protein Microenvironment in Biopsy Tssue. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Falk C, Daemen K, Keil J, Lehner F, Haller H, Schmitz J, Bräsen J-H, Blume C. Rejection of Human Kidney Allografts According to BANFF Classification Is Associated with a Chemokine-Enriched Protein Microenvironment in Biopsy Tssue. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/rejection-of-human-kidney-allografts-according-to-banff-classification-is-associated-with-a-chemokine-enriched-protein-microenvironment-in-biopsy-tssue/. Accessed November 22, 2024.« Back to 2017 American Transplant Congress