ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on X

Kidney Week

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
  • 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
  • Stallone, Giovanni, University of Foggia, Foggia, Italy
  • Grandaliano, Giuseppe, Nefrologia/Dialisi/Trapianto, Foggia, 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.