Ige-Mediated Immune Response And 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-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.