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J Allergy Clin Immunol. 2019 Jan;143(1):335-345.e12. doi: 10.1016/j.jaci.2018.06.034. Epub 2018 Aug 9.

Allograft rejection is associated with development of functional IgE specific for donor MHC antigens.

Author information

1
Section of Transplantation Immunology, Department of Surgery, Medical University of Vienna, Vienna, Austria.
2
Section of Transplantation Immunology, Department of Surgery, Medical University of Vienna, Vienna, Austria; Cardiac Surgery Laboratory, Medical University of Vienna, Vienna, Austria.
3
Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
4
Institute of Clinical Pathology, Medical University of Vienna, Vienna, Austria.
5
Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center of Physiology and Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
6
Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
7
Department for Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria.
8
Department of Surgery, University of Cambridge, Cambridge, United Kingdom.
9
Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
10
Section of Transplantation Immunology, Department of Surgery, Medical University of Vienna, Vienna, Austria. Electronic address: Thomas.Wekerle@meduniwien.ac.at.

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.

KEYWORDS:

IgE; Transplantation; alloreactivity; donor-specific antibodies; humoral rejection; immunology

PMID:
30009843
DOI:
10.1016/j.jaci.2018.06.034
[Indexed for MEDLINE]
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