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Original ArticlesTransplantation
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IgE-Mediated Immune Response and Antibody-Mediated Rejection

Federica Rascio, Paola Pontrelli, Giuseppe Stefano Netti, Elisabetta Manno, Barbara Infante, Simona Simone, Giuseppe Castellano, Elena Ranieri, Michela Seveso, Emanuele Cozzi, Loreto Gesualdo, Giovanni Stallone and Giuseppe Grandaliano
CJASN October 2020, 15 (10) 1474-1483; DOI: https://doi.org/10.2215/CJN.02870320
Federica Rascio
1Department of Medical and Surgical Sciences, Nephrology Dialysis and Transplantation Unit, University of Foggia, Foggia, Italy
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Paola Pontrelli
2Department of Emergency and Organ Transplantation, Nephrology, Dialysis and Transplantation Unit, University of Bari “A. Moro,” Bari, Italy
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Giuseppe Stefano Netti
3Department of Medical and Surgical Sciences, Clinical Pathology Unit, University of Foggia, Foggia, Italy
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Elisabetta Manno
1Department of Medical and Surgical Sciences, Nephrology Dialysis and Transplantation Unit, University of Foggia, Foggia, Italy
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Barbara Infante
1Department of Medical and Surgical Sciences, Nephrology Dialysis and Transplantation Unit, University of Foggia, Foggia, Italy
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Simona Simone
2Department of Emergency and Organ Transplantation, Nephrology, Dialysis and Transplantation Unit, University of Bari “A. Moro,” Bari, Italy
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Giuseppe Castellano
1Department of Medical and Surgical Sciences, Nephrology Dialysis and Transplantation Unit, University of Foggia, Foggia, Italy
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Elena Ranieri
3Department of Medical and Surgical Sciences, Clinical Pathology Unit, University of Foggia, Foggia, Italy
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Michela Seveso
4Department of Cardiac, Thoracic and Vascular Sciences, Transplant Immunology Unit, Padova University Hospital, Padova, Italy
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Emanuele Cozzi
4Department of Cardiac, Thoracic and Vascular Sciences, Transplant Immunology Unit, Padova University Hospital, Padova, Italy
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Loreto Gesualdo
2Department of Emergency and Organ Transplantation, Nephrology, Dialysis and Transplantation Unit, University of Bari “A. Moro,” Bari, Italy
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Giovanni Stallone
1Department of Medical and Surgical Sciences, Nephrology Dialysis and Transplantation Unit, University of Foggia, Foggia, Italy
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Giuseppe Grandaliano
5Department of Translational Medicine and Surgery, Nephrology Unit, Università Cattolica del Sacro Cuore, Rome, Italy
6Department of Medical and Surgical Sciences, Nephrology Unit, Fondazione Policlinico Universitario “A. Gemelli” Scientific Institute of Recovery and Care, Rome, Italy
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Abstract

Background and objectives Active antibody-mediated rejection is the main cause of kidney transplant loss, sharing with SLE the alloimmune response and the systemic activation of the IFN-α pathway. IgE-mediated immune response plays a key role in the development of SLE nephritis and is associated with IFN-α secretion. The aim of our study was to investigate IgE-mediated immune response in antibody-mediated rejection.

Design, setting, participants, & measurements This was a cross-sectional study of 56 biopsy-proven antibody-mediated rejection study participants, 80 recipients with normal graft function/histology (control), 16 study participants with interstitial fibrosis/tubular atrophy, and six participants with SLE. We evaluated graft IgE deposition, tryptase (a mast cell marker), and CD203 (a specific marker of activated basophils) by immunofluorescence/confocal microscopy. In addition, we measured serum concentration of human myxovirus resistance protein 1, an IFN-α–induced protein, and anti-HLA IgE.

Results We observed a significantly higher IgE deposition in tubules and glomeruli in antibody-mediated rejection (1766±79 pixels) and SLE (1495±43 pixels) compared with interstitial fibrosis/tubular atrophy (582±122 pixels) and control (253±50 pixels). Patients with antibody-mediated rejection, but not control patients and patients with interstitial fibrosis/tubular atrophy, presented circulating anti-HLA IgE antibodies, although with a low mean fluorescence intensity. In addition, immunofluorescence revealed the presence of both mast cells and activated basophils in antibody-mediated rejection but not in control and interstitial fibrosis/tubular atrophy. The concentration of circulating basophils was significantly higher in antibody-mediated rejection compared with control and interstitial fibrosis/tubular atrophy. MxA serum levels were significantly higher in antibody-mediated rejection compared with control and correlated with the extent of IgE deposition.

Conclusions Our data suggest that IgE deposition and the subsequent recruitment of basophils and mast cells within the kidney transplant might play a role in antibody-mediated rejection.

  • chronic rejection
  • mast cells
  • basophils
  • interferon alpha
  • IgE
  • Received March 5, 2020.
  • Accepted July 8, 2020.
  • Copyright © 2020 by the American Society of Nephrology
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Clinical Journal of the American Society of Nephrology: 15 (10)
Clinical Journal of the American Society of Nephrology
Vol. 15, Issue 10
October 07, 2020
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IgE-Mediated Immune Response and Antibody-Mediated Rejection
Federica Rascio, Paola Pontrelli, Giuseppe Stefano Netti, Elisabetta Manno, Barbara Infante, Simona Simone, Giuseppe Castellano, Elena Ranieri, Michela Seveso, Emanuele Cozzi, Loreto Gesualdo, Giovanni Stallone, Giuseppe Grandaliano
CJASN Oct 2020, 15 (10) 1474-1483; DOI: 10.2215/CJN.02870320

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IgE-Mediated Immune Response and Antibody-Mediated Rejection
Federica Rascio, Paola Pontrelli, Giuseppe Stefano Netti, Elisabetta Manno, Barbara Infante, Simona Simone, Giuseppe Castellano, Elena Ranieri, Michela Seveso, Emanuele Cozzi, Loreto Gesualdo, Giovanni Stallone, Giuseppe Grandaliano
CJASN Oct 2020, 15 (10) 1474-1483; DOI: 10.2215/CJN.02870320
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Keywords

  • chronic rejection
  • mast cells
  • basophils
  • interferon alpha
  • IgE

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