Prospective assessment of pre-existing and de novo anti-HLA IgE in kidney, liver, lung and heart transplantation

Copyright © 2023 Mucha, Cho, Weijler, Muckenhuber, Hofmann, Wahrmann, Heinzel, Linhart, Gattinger, Valenta, Berlakovich, Zuckermann, Jaksch, Oberbauer and Wekerle..

Introduction: Antibody mediated rejection (ABMR) is a major factor limiting outcome after organ transplantation. Anti-HLA donor-specific antibodies (DSA) of the IgG isotype are mainly responsible for ABMR. Recently DSA of the IgE isotype were demonstrated in murine models as well as in a small cohort of sensitized transplant recipients. In the present study, we aimed to determine the frequency of pre-existing and de novo anti-HLA IgE antibodies in a cohort of 105 solid organ transplant recipients.

Methods: We prospectively measured anti-HLA IgE antibodies in a cohort of kidney (n=60), liver, heart and lung (n=15 each) transplant recipients before and within one-year after transplantation, employing a single-antigen bead assay for HLA class I and class II antigens. Functional activity of anti-HLA IgE antibodies was assessed by an in vitro mediator release assay. Antibodies of the IgG1-4 subclasses and Th1 and Th2 cytokines were measured in anti-HLA IgE positive patients.

Results: Pre-existing anti-HLA IgE antibodies were detected in 10% of renal recipients (including 3.3% IgE-DSA) and in 4.4% of non-renal solid organ transplant recipients (heart, liver and lung cohort). Anti-HLA IgE occurred only in patients that were positive for anti-HLA IgG, and most IgE positive patients had had a previous transplant. Only a small fraction of patients developed de novo anti-HLA IgE antibodies (1.7% of kidney recipients and 4.4% of non-renal recipients), whereas no de novo IgE-DSA was detected. IgG subclass antibodies showed a distinct pattern in patients who were positive for anti-HLA IgE. Moreover, patients with anti-HLA IgE showed elevated Th2 and also Th1 cytokine levels. Serum from IgE positive recipients led to degranulation of basophils in vitro, demonstrating functionality of anti-HLA IgE.

Discussion: These data demonstrate that anti-HLA IgE antibodies occur at low frequency in kidney, liver, heart and lung transplant recipients. Anti-HLA IgE development is associated with sensitization at the IgG level, in particular through previous transplants and distinct IgG subclasses. Taken together, HLA specific IgE sensitization is a new phenomenon in solid organ transplant recipients whose potential relevance for allograft injury requires further investigation.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:14

Enthalten in:

Frontiers in immunology - 14(2023) vom: 21., Seite 1179036

Sprache:

Englisch

Beteiligte Personen:

Mucha, Jasmin [VerfasserIn]
Cho, Ara [VerfasserIn]
Weijler, Anna Marianne [VerfasserIn]
Muckenhuber, Moritz [VerfasserIn]
Hofmann, Amun Georg [VerfasserIn]
Wahrmann, Markus [VerfasserIn]
Heinzel, Andreas [VerfasserIn]
Linhart, Birgit [VerfasserIn]
Gattinger, Pia [VerfasserIn]
Valenta, Rudolf [VerfasserIn]
Berlakovich, Gabriela [VerfasserIn]
Zuckermann, Andreas [VerfasserIn]
Jaksch, Peter [VerfasserIn]
Oberbauer, Rainer [VerfasserIn]
Wekerle, Thomas [VerfasserIn]

Links:

Volltext

Themen:

37341-29-0
Antibody-mediated rejection
Antilymphocyte Serum
Clinical
Donor-specific antibodies (DSA)
IgE
Immunoglobulin E
Immunoglobulin G
Immunology
Immunosuppressive Agents
Journal Article
Kidney transplantation
Organ transplantation
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 22.09.2023

Date Revised 22.09.2023

published: Electronic-eCollection

Citation Status MEDLINE

doi:

10.3389/fimmu.2023.1179036

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM362282250