High Concentrations of CXCL9 and CXCL10 Chemokines but Not CXCL8 (IL-8), IL-6, TNF-a or IFN-g in Biopsy Tissue Are Associated with Pathological Staging of Rejection After Kidney Transplantation.
1Institute of Transplant Immunology, IFB-Tx, Hannover Medical School, Hannover, Germany
2Department of Abdominal and Transplantation Surgery, Hannover Medical School, Hannover, Deutschland, Germany
3Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Deutschland, Germany
4Institute of Pathology, Hannover Medical School, Hannover, Deutschland, Germany
5Institute of Technical Chemistry, Leibniz University Hannover, Hannover, Deutschland, Germany.
Meeting: 2016 American Transplant Congress
Abstract number: B1
Keywords: Immunogenicity, Inflammation, Kidney transplantation
Session Information
Date: Sunday, June 12, 2016
Session Name: Poster Session B: Allograft Rejection, Tolerance, and Xenotransplantation
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Halls C&D
Background: Extensive expression profiling efforts of biopsy tissue after kidney transplantation indicate that rejection, especially antibody-mediated rejection (AMR) can be defined by distinct signatures. Thus, 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 biopsies of capsule vs. cortical and medullary regions and associated the concentrations of pro-inflammatory cytokines with pathological staging.
Methods: Within our biopsy program, 37 secondary snap-frozen kidney biopsies were obtained from transplant recipients at 2 to 20 years after Tx with ethical approval,informed consent. Protein lysates of capsule, cortical and medullary biopsy tissues were analyzed for 50 proteins by multiplex arrays. Histopathological evaluation of primary biopsies was performed according to BANFF criteria (14 unsuspicious, 4 TCMR, 5 boderline, 14 AMR).
Results: The protein microenvironment differed significantly between kidney caspular, cortical and medullary regions even in unsuspicious biopsies, for example SCGF (p<0.02). In contrast, some proinflammatory cytokines like IL-6, IL-8(CXCL8), IFN-g, TNF-a were hardly detectable and did not differ between regions of unsuspicious and rejection biopsies. However, significantly higher concentrations of chemokines CXCL9, CXCL10 were detected in cortical and medullary regions of biopsies in the rejection group (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 and 10 confirm their qualification as biomarker candidate also at the protein level while typical T cell-derived cytokines seem to perform rather poorly as biomarker candidates.
CITATION INFORMATION: Falk C, Neudörfl C, Daemen K, Keil J, Lehner F, Haller H, Schmitz J, Blume C, Bräsen J.-H. High Concentrations of CXCL9 and CXCL10 Chemokines but Not CXCL8 (IL-8), IL-6, TNF-a or IFN-g in Biopsy Tissue Are Associated with Pathological Staging of Rejection After Kidney Transplantation. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:
Falk C, Neudörfl C, Daemen K, Keil J, Lehner F, Haller H, Schmitz J, Blume C, Bräsen J-H. High Concentrations of CXCL9 and CXCL10 Chemokines but Not CXCL8 (IL-8), IL-6, TNF-a or IFN-g in Biopsy Tissue Are Associated with Pathological Staging of Rejection After Kidney Transplantation. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/high-concentrations-of-cxcl9-and-cxcl10-chemokines-but-not-cxcl8-il-8-il-6-tnf-a-or-ifn-g-in-biopsy-tissue-are-associated-with-pathological-staging-of-rejection-after-kidney-transplantation/. Accessed January 20, 2021.« Back to 2016 American Transplant Congress