Federica Rascio1, Paola Pontrelli2, Giuseppe Stefano Netti3, Elisabetta Manno1, Barbara Infante1, Simona Simone4, Giuseppe Castellano1, Elena Ranieri3, Michela Seveso5, Emanuele Cozzi5, Loreto Gesualdo4, Giovanni Stallone1, Giuseppe Grandaliano6,7. 1. Department of Medical and Surgical Sciences, Nephrology Dialysis and Transplantation Unit, University of Foggia, Foggia, Italy. 2. Department of Emergency and Organ Transplantation, Nephrology, Dialysis and Transplantation Unit, University of Bari "A. Moro," Bari, Italy paola.pontrelli@uniba.it. 3. Department of Medical and Surgical Sciences, Clinical Pathology Unit, University of Foggia, Foggia, Italy. 4. Department of Emergency and Organ Transplantation, Nephrology, Dialysis and Transplantation Unit, University of Bari "A. Moro," Bari, Italy. 5. Department of Cardiac, Thoracic and Vascular Sciences, Transplant Immunology Unit, Padova University Hospital, Padova, Italy. 6. Department of Translational Medicine and Surgery, Nephrology Unit, Università Cattolica del Sacro Cuore, Rome, Italy. 7. Department of Medical and Surgical Sciences, Nephrology Unit, Fondazione Policlinico Universitario "A. Gemelli" Scientific Institute of Recovery and Care, Rome, Italy.
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.
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.
Authors: Rachel Ettinger; Jodi L Karnell; Jill Henault; Santosh K Panda; Jeffrey M Riggs; Roland Kolbeck; Miguel A Sanjuan Journal: Autoimmunity Date: 2017-02 Impact factor: 2.815
Authors: Jill Henault; Jeffrey M Riggs; Jodi L Karnell; Vladimir M Liarski; Jianqing Li; Lena Shirinian; Linda Xu; Kerry A Casey; Michael A Smith; Deepak B Khatry; Liat Izhak; Lorraine Clarke; Ronald Herbst; Rachel Ettinger; Michelle Petri; Marcus R Clark; Tomas Mustelin; Roland Kolbeck; Miguel A Sanjuan Journal: Nat Immunol Date: 2015-12-21 Impact factor: 25.606