A Potential Role for IgE-Mediated Immune Response in the Pathogenesis of Chronic Antibody-Mediated Rejection

F. Rascio¹, P. Pontrelli², G. S. Netti³, E. Manno¹, B. Infante¹, S. Simone², G. Castellano², M. Seveso⁴, E. Cozzi⁴, L. Gesualdo², G. Stallone¹, G. Grandaliano¹

¹Department of Medical and Surgical Sciences, Nephrology Dialysis and Transplantation Unit, University of Foggia, Foggia, Italy, ²Department of Emergency, and Organ Transplantation, Nephrology, Dialysis and Transplantation Unit, University of Bari, Bari, Italy, ³Dept. of Medical and Surgical Sciences, Clinical Pathology Unit, University of Foggia, Foggia, Italy, ⁴Department of Cardiac, Thoracic and Vascular Sciences, Transplant Immunology Unit, University of Padua, Padova, Italy

Meeting: 2019 American Transplant Congress

Abstract number: 485

Keywords: Biopsy, Interferon (IFN), Kidney transplantation, Rejection

Session Information

Session Name: Concurrent Session: Innate Immunity; Chemokines, Cytokines, Complement

Session Type: Concurrent Session

Date: Tuesday, June 4, 2019

Session Time: 2:30pm-4:00pm

Presentation Time: 3:30pm-3:42pm

Location: Room 310

*Purpose: Chronic antibody-mediated rejection (CAMR) is the main cause of graft loss and shares with systemic lupus erythematosus (SLE) the antibody-mediated kidney damage and the systemic activation of the interferon-alpha (IFN-alpha) pathway. IgE-mediated immune response plays a key role in the development of SLE nephritis and is associated with IFN-alpha secretion. The aim of our study was to investigate IgE-mediated immune response in CAMR grafts.

*Methods: We enrolled 40 biopsy-proven CAMR patients, 15 transplant recipients with normal graft function/histology (CTRL), 15 patients with interstitial fibrosis/tubular atrophy (IFTA) and 6 SLE patients.

*Results: We observed a significant increase in tubular and glomerular deposition of IgE in CAMR and SLE patients compared with IFTA and CTRL (p<0.001). Interestingly, the imunofluorescence for tryptase, a mast cells marker, and CD203c, a specific marker of basophil activation, revealed a significant infiltration of both cell types in CAMR grafts and a lesser extent in SLE kidneys (p=0.02). We also observed that the absolute number of circulating basophils was significantly increased in CAMR compared to CTRL and IFTA. Serum levels of MxA, an IFN-alpha-induced protein, were significantly higher in CAMR compared to CTRL patients (p=0.002) and directly associated with the extent of IgE deposits in the graft (r=0.347, p=0.01). Since it has been shown that IgE immune complex can induce IFN-alpha production by plasmacytoid dendritic cells (pDC), we investigated the presence of these antigen-presenting cells in graft biopsies. As in SLE, also in CAMR tissue we observed a significant increase in interstitial pDCs closely associated to IgE deposits.

*Conclusions: Our data suggest that IgE deposition and the subsequent recruitment of basophils and mast cells within the graft may play a key pathogenic role in CAMR. The genesis of these events appears to be linked, as in SLE, to the systemic activation of the IFN-alpha pathway.

To cite this abstract in AMA style:

Rascio F, Pontrelli P, Netti GS, Manno E, Infante B, Simone S, Castellano G, Seveso M, Cozzi E, Gesualdo L, Stallone G, Grandaliano G. A Potential Role for IgE-Mediated Immune Response in the Pathogenesis of Chronic Antibody-Mediated Rejection [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/a-potential-role-for-ige-mediated-immune-response-in-the-pathogenesis-of-chronic-antibody-mediated-rejection/. Accessed May 9, 2025.

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