Chemokine CXCL13 as a New Systemic Biomarker for B-Cell Involvement in Acute T Cell-Mediated Kidney Allograft Rejection
Schiffer L, Wiehler F, Bräsen JH, Gwinner W, Greite R, Kreimann K, Thorenz A, Derlin K, Teng B, Rong S, von Vietinghoff S, Haller H, Mengel M, Pape L, Lerch C, Schiffer M, Gueler F (2019)
Publication Type: Journal article
Publication year: 2019
Journal
Book Volume: 20
Journal Issue: 10
DOI: 10.3390/ijms20102552
Abstract
The presence of B-cell clusters in allogenic T cell-mediated rejection (TCMR) of kidney allografts is linked to more severe disease entities. In this study we characterized B-cell infiltrates in patients with TCMR and examined the role of serum CXCL-13 in these patients and experimentally. CXCL-13 serum levels were analyzed in 73 kidney allograft recipients at the time of allograft biopsy. In addition, four patients were evaluated for CXCL13 levels during the first week after transplantation. ELISA was done to measure CXCL-13 serum levels. For further mechanistic understanding, a translational allogenic kidney transplant (ktx) mouse model for TCMR was studied in BalbC recipients of fully mismatched transplants with C57BL/6 donor kidneys. CXCL-13 serum levels were measured longitudinally, CD20 and CD3 composition and CXCL13 mRNA in tissue were examined by flow cytometry and kidneys were examined by histology and immunohistochemistry. We found significantly higher serum levels of the B-cell chemoattractant CXCL13 in patients with TCMR compared to controls and patients with borderline TCMR. Moreover, in patients with acute rejection within the first week after ktx, a >5-fold CXCL13 increase was measured and correlated with B-cell infiltrates in the biopsies. In line with the clinical findings, TCMR in mice correlated with increased systemic serum-CXCL13 levels. Moreover, renal allografts had significantly higher CXCL13 mRNA expression than isogenic controls and showed interstitial CD20+ B-cell clusters and CD3+ cell infiltrates accumulating in the vicinity of renal vessels. CXCL13 blood levels correlate with B-cell involvement in TCMR and might help to identify patients at risk of a more severe clinical course of rejection.
Authors with CRIS profile
Involved external institutions
Medizinische Hochschule Hannover (MHH) / Hannover Medical School
Germany (DE)
University of Alberta
Canada (CA)
Germany (DE)
University of Alberta
Canada (CA)
How to cite
APA:
Schiffer, L., Wiehler, F., Bräsen, J.H., Gwinner, W., Greite, R., Kreimann, K.,... Gueler, F. (2019). Chemokine CXCL13 as a New Systemic Biomarker for B-Cell Involvement in Acute T Cell-Mediated Kidney Allograft Rejection. International Journal of Molecular Sciences, 20(10). https://dx.doi.org/10.3390/ijms20102552
MLA:
Schiffer, Lena, et al. "Chemokine CXCL13 as a New Systemic Biomarker for B-Cell Involvement in Acute T Cell-Mediated Kidney Allograft Rejection." International Journal of Molecular Sciences 20.10 (2019).
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