1. Chemokine CXCL13 as a New Systemic Biomarker for B-Cell Involvement in Acute T Cell-Mediated Kidney Allograft Rejection
- Author
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Flavia Wiehler, Robert Greite, Lena Schiffer, Katja Derlin, Wilfried Gwinner, Lars Pape, Christian Lerch, Mario Schiffer, Beina Teng, Michael Mengel, Anja Thorenz, Hermann Haller, Faikah Gueler, Kirill Kreimann, Jan Hinrich Bräsen, Sibylle von Vietinghoff, and Song Rong
- Subjects
Graft Rejection ,Male ,0301 basic medicine ,Pathology ,T-Lymphocytes ,030230 surgery ,lcsh:Chemistry ,Mice ,0302 clinical medicine ,lcsh:QH301-705.5 ,Spectroscopy ,Kidney transplantation ,B-Lymphocytes ,Mice, Inbred BALB C ,Kidney ,allograft rejection ,General Medicine ,CXCL13 ,Middle Aged ,Computer Science Applications ,medicine.anatomical_structure ,Immunohistochemistry ,Biomarker (medicine) ,Adult ,medicine.medical_specialty ,T cell ,kidney transplantation ,Article ,Catalysis ,Inorganic Chemistry ,03 medical and health sciences ,medicine ,Animals ,Humans ,ddc:610 ,Physical and Theoretical Chemistry ,Molecular Biology ,B cell ,business.industry ,Organic Chemistry ,T cell-mediated rejection ,medicine.disease ,Chemokine CXCL13 ,Mice, Inbred C57BL ,Transplantation ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,B-cell attracting chemokine ,business ,Biomarkers - 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.
- Published
- 2019