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IgE-Mediated Immune Response and Antibody-Mediated Rejection.

Authors :: Rascio F
Pontrelli P
Netti GS
Manno E
Infante B
Simone S
Castellano G
Ranieri E
Seveso M
Cozzi E
Gesualdo L
Stallone G
Grandaliano G
Source :: Clinical journal of the American Society of Nephrology : CJASN [Clin J Am Soc Nephrol] 2020 Oct 07; Vol. 15 (10), pp. 1474-1483. Date of Electronic Publication: 2020 Sep 09.
Publication Year :: 2020
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.<br />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.<br />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.<br />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.<br /> (Copyright © 2020 by the American Society of Nephrology.)