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Open AccessArticle

Chemokine CXCL13 as a New Systemic Biomarker for B-Cell Involvement in Acute T Cell-Mediated Kidney Allograft Rejection

1
Nephrology, Hannover Medical School, 30625 Hannover, Germany
2
Pediatric Nephrology, Hannover Medical School, 30625 Hannover, Germany
3
Pathology, Hannover Medical School, 30625 Hannover, Germany
4
Radiology, Hannover Medical School, 30625 Hannover, Germany
5
Laboratory Medicine & Pathology, University of Alberta, Edmonton, AB T6G 2R3, Canada
6
Nephrology and Hypertension, University Hospital Erlangen, 91054 Erlangen, Gerrmany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(10), 2552; https://doi.org/10.3390/ijms20102552
Received: 26 March 2019 / Revised: 13 May 2019 / Accepted: 19 May 2019 / Published: 24 May 2019
(This article belongs to the Special Issue Kidney Inflammation, Injury and Regeneration)
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. View Full-Text
Keywords: B-cell attracting chemokine; CXCL13; kidney transplantation; allograft rejection; T cell-mediated rejection B-cell attracting chemokine; CXCL13; kidney transplantation; allograft rejection; T cell-mediated rejection
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MDPI and ACS Style

Schiffer, L.; Wiehler, F.; Bräsen, J.H.; 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. Chemokine CXCL13 as a New Systemic Biomarker for B-Cell Involvement in Acute T Cell-Mediated Kidney Allograft Rejection. Int. J. Mol. Sci. 2019, 20, 2552. https://doi.org/10.3390/ijms20102552

AMA Style

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. Chemokine CXCL13 as a New Systemic Biomarker for B-Cell Involvement in Acute T Cell-Mediated Kidney Allograft Rejection. International Journal of Molecular Sciences. 2019; 20(10):2552. https://doi.org/10.3390/ijms20102552

Chicago/Turabian Style

Schiffer, Lena; Wiehler, Flavia; Bräsen, Jan H.; Gwinner, Wilfried; Greite, Robert; Kreimann, Kirill; Thorenz, Anja; Derlin, Katja; Teng, Beina; Rong, Song; von Vietinghoff, Sibylle; Haller, Hermann; Mengel, Michael; Pape, Lars; Lerch, Christian; Schiffer, Mario; Gueler, Faikah. 2019. "Chemokine CXCL13 as a New Systemic Biomarker for B-Cell Involvement in Acute T Cell-Mediated Kidney Allograft Rejection" Int. J. Mol. Sci. 20, no. 10: 2552. https://doi.org/10.3390/ijms20102552

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