Allograft rejection is associated with development of functional IgE specific for donor MHC antigens.
Allografts
Animals
Female
Graft Rejection
/ immunology
Heart Transplantation
Histocompatibility Antigens Class I
/ immunology
Histocompatibility Antigens Class II
/ immunology
Humans
Immunoglobulin E
/ immunology
Immunoglobulin G
/ immunology
Kidney Transplantation
Male
Mice
Mice, Inbred BALB C
Skin Transplantation
IgE
Transplantation
alloreactivity
donor-specific antibodies
humoral rejection
immunology
Journal
The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
26
07
2017
revised:
07
06
2018
accepted:
14
06
2018
pubmed:
17
7
2018
medline:
13
11
2019
entrez:
17
7
2018
Statut:
ppublish
Résumé
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. This study aimed to investigate whether MHC-specific antibodies of the IgE isotype are induced during allograft rejection. 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). 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 These results demonstrate that MHC/HLA-specific IgE develops during an alloresponse and is functional in mediating effector mechanisms.
Sections du résumé
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
CONCLUSION
These results demonstrate that MHC/HLA-specific IgE develops during an alloresponse and is functional in mediating effector mechanisms.
Identifiants
pubmed: 30009843
pii: S0091-6749(18)30997-7
doi: 10.1016/j.jaci.2018.06.034
pii:
doi:
Substances chimiques
Histocompatibility Antigens Class I
0
Histocompatibility Antigens Class II
0
Immunoglobulin G
0
Immunoglobulin E
37341-29-0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
335-345.e12Subventions
Organisme : Austrian Science Fund FWF
ID : F 4605
Pays : Austria
Organisme : British Heart Foundation
ID : FS/12/87/29899
Pays : United Kingdom
Organisme : Department of Health
ID : RP-2017-08-ST2-002
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.