Allograft rejection is associated with development of functional IgE specific for donor MHC antigens - 04/01/19
Abstract |
Background |
Donor-specific antibodies of the IgG isotype are measured routinely for diagnostic purposes in renal transplant recipients and are associated with antibody-mediated rejection and long-term graft loss.
Objective |
This study aimed to investigate whether MHC-specific antibodies of the IgE isotype are induced during allograft rejection.
Methods |
Anti-MHC/HLA IgE levels were measured in sera of mice grafted with skin or heart transplants from various donor strains and in sera of kidney transplant patients with high levels of HLA IgG. Mediator release was triggered in vitro by stimulating basophils that were coated with murine or human IgE-positive serum, respectively, with specific recombinant MHC/HLA antigens. Kidney tissue samples obtained from organ donors were analyzed by using flow cytometry for cells expressing the high-affinity receptor for IgE (FcεRI).
Results |
Donor MHC class I– and MHC class II–specific IgE was found on acute rejection of skin and heart grafts in several murine strain combinations, as well as during chronic antibody-mediated heart graft rejection. Anti-HLA IgE, including donor HLA class I and II specificities, was identified in a group of sensitized transplant recipients. Murine and human anti-MHC/HLA IgE triggered mediator release in coated basophils on stimulation with specific MHC/HLA antigens. HLA-specific IgE was not linked to atopy, and allergen-specific IgE present in allergic patients did not cross-react with HLA antigens. FcεRI+ cells were found in the human renal cortex and medulla and provide targets for HLA-specific IgE.
Conclusion |
These results demonstrate that MHC/HLA-specific IgE develops during an alloresponse and is functional in mediating effector mechanisms.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : Transplantation, immunology, alloreactivity, humoral rejection, IgE, donor-specific antibodies
Abbreviations used : ABMR, DSA, HRP, MFI, PE, RBL, SAB
Plan
| Supported by the Austrian Science Fund (FWF; projects TRP151-B19 and W1212 to T.W., project P21989-B11 to U.B, and project F4605 to R.V.) and the Medical Scientific Fund of the Mayor of the City of Vienna (project 13051 to T.W.). R.V. is recipient of a Megagrant of the Government of the Russian Federation (grant no. 14.W03.31.0024). |
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| Disclosure of potential conflict of interest: R. Valenta has received research grants from Biomay AG and Viravaxx and serves as a consultant for both companies. The rest of the other authors declare that they have no relevant conflicts of interest to disclose. |
Vol 143 - N° 1
P. 335 - janvier 2019 Retour au numéro
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