Abstract: FR-PO1010

A Role for IgE-Mediated Immune Response in the Pathogenesis of Chronic Antibody-Mediated Rejection (CAMR)

Session Information

Category: Transplantation

  • 1701 Transplantation: Basic and Experimental

Authors

  • Rascio, F., University of Foggia, Foggia, Italy
  • Stallone, Giovanni, University of Foggia, Foggia, Italy
  • Grandaliano, Giuseppe, Nefrologia/Dialisi/Trapianto, Foggia, Italy
  • Pontrelli, Paola, University of Bari-Dept. of Emergency and Organ Transplantation, Bari, Italy
  • Manno, Elisabetta, University of Foggia, Foggia, Italy
  • Netti, Giuseppe S., University of Foggia, Foggia, Italy
  • Infante, Barbara, University of Foggia, Foggia, Italy
  • Cocina, Giulia, University of Foggia, Foggia, Italy
  • Simone, Simona, University of Bari, Altamura, Bari, Italy
  • Castellano, Giuseppe, University of Bari, Altamura, Bari, Italy
  • Gesualdo, Loreto, University of Bari, Altamura, Bari, Italy
Background

CAMR is the main cause of graft loss and share with systemic lupus erythematosus (SLE), an autoimmune disease, the antibody-mediated kidney damage, the development of autoantibodies, and the activation of the interferon-alpha (IFN-alpha) pathway. IgE-mediated immune response play 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 (pts), 15 transplant pts with normal graft function/histology (CTRL), 15 pts with interstitial fibrosis/tubular atrophy (IFTA) and 6 SLE pts. IgE deposition as well as recruitment of basophil and mast cells, the two main cell types activated by IgE, were studied by confocal microscopy. The IFN-alpha response was assessed measuring serum MxA, an IFN-alpha-induced protein, by ELISA.

Results

We observed a significant increase in tubular and glomerular deposition of IgE in CAMR patients (1876±197 pixels/area) and SLE (1678±178 pixels/area) compared with IFTA (379±87 pixels/area) and CTRL (355±93 pixels/area) (p<.001). Interestingly, the stainings for triptase, a marker of mast cells, and CD203c, a specific marker of basophil activation, revealed a significant infiltration of both cell types IgE in CAMR grafts (triptase+cells/field: CAMR 15±5 vs. LES 3.0±.4 and CTRL 0.2±0.4, p=.02. Cd203c+cells: CAMR 21±5 vs. LES 2.0±.4 and CTRL .2±.4, p=.02). We also observed that the absolute number of circulating basophils was significantly increased in CAMR (48±3/ul) compared to CTRL (20±1/ul) and IFTA (15±.5/ul, p=.02). MxA serum levels were significantly higher in CAMR compared to CTRL (123.3±22.6 vs 42.9±37.9 ng/ml, p=.002) and directly associated with the extent of IgE deposits (r=.347, p=.01).

Conclusion

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.

Funding

  • Government Support - Non-U.S.