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Analysis of the IgVH genes in T cell-mediated and antibody-mediated rejection of the kidney graft
  1. Cristiana Bellan1,
  2. Teresa Amato1,
  3. Mario Carmellini2,
  4. Monica Onorati1,
  5. Alessandro D'Amuri1,
  6. Lorenzo Leoncini1,
  7. Maria Teresa del Vecchio1
  1. 1Section of Pathological Anatomy, Department of Human Pathology and Oncology, University of Siena, Siena, Italy
  2. 2Section of Surgery, Department of Surgery and Bioengineering, University of Siena, Siena, Italy
  1. Correspondence to Professor Lorenzo Leoncini, Section of Pathological Anatomy, Department of Human Pathology and Oncology, Via delle Scotte, 6, 53100 Siena, Italy; leoncinil{at}unisi.it

Abstract

Aims Grafts have been shown to be sites where the alloimmune response develops in a direct interaction between the targeted tissue and the immune effectors. An important issue in renal rejection is B cell infiltrate that may contribute to the development or persistence of rejection. Analysis of gene-expression patterns also provides a window on the biology and pathogenesis of renal allograft rejection.

Methods To better understand the role exerted by B cells in a renal acute rejection, the authors analysed the IgVH gene repertoire in six cases of transplanted kidneys with acute T cell-mediated rejection (TCMR), three of which were associated with antibody-mediated rejection (ABMR).

Results The authors found mutated and unmutated sequences, without any evidence of clonal relationships, in all patients with TCMR alone and in two of the three cases with both acute TCMR and ABMR. The remaining patient showed glomerular inflammation and thrombosis, with diffuse C4d glomerular and peritubular capillary deposition, and hypermutated V region genes.

Conclusions These results suggest that there is more than one pathway to the onset and perpetuation of CD20 (+) B cells infiltration in acute rejection; furthermore, the CD20 (+) B cells’ clonal expansion may be responsible for a more severe pattern of ABMR, through immune-mediated tissue damage.

  • T-cell-mediated rejection
  • antibody-mediated rejection
  • IgVH gene analysis
  • immunoglobulin
  • kidney
  • rejection
  • transplantation

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Footnotes

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval Ethics approval was provided by the Azienda Ospedaliera Universitaria Senese, University of Siena.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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