IgE-Mediated Immune Response and Antibody-Mediated Rejection

Author: Rascio, F.; Pontrelli, P.; Netti, G.S.; Manno, E.; Infante, B.; Simone, S.; Castellano, G.; Ranieri, E.; Seveso, M.; Cozzi, E.; Gesualdo, L.; Stallone, G.; Grandaliano, G.

Description: 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-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 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-alpha-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.

Subject headings: IgE; basophils; chronic rejection; interferon alpha; mast cells

Publication year: 2020

Journal or book title: Clinical Journal of the American Society of Nephrology : CJASN

Volume: 15

Issue: 10

Pages: 1474-1483

Find the full text : https://cjasn.asnjournals.org/content/15/10/1474.abstract

Find more like this one (cited by): https://scholar.google.com/scholar?cites=14245573633972246649&as_sdt=1000005&sciodt=0,16&hl=en

Type: Journal Article

Serial number: 3033