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 |
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Erscheinungsjahr: |
2023 |
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Erschienen: |
2023 |
Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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Enthalten in: |
Frontiers in immunology - 14(2023) vom: 21., Seite 1179036 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Mucha, Jasmin [VerfasserIn] |
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Links: |
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Anmerkungen: |
Date Completed 22.09.2023 Date Revised 22.09.2023 published: Electronic-eCollection Citation Status MEDLINE |
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doi: |
10.3389/fimmu.2023.1179036 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM362282250 |
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520 | |a Copyright © 2023 Mucha, Cho, Weijler, Muckenhuber, Hofmann, Wahrmann, Heinzel, Linhart, Gattinger, Valenta, Berlakovich, Zuckermann, Jaksch, Oberbauer and Wekerle. | ||
520 | |a 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 | ||
520 | |a 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 | ||
520 | |a 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 | ||
520 | |a 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 | ||
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650 | 4 | |a donor-specific antibodies (DSA) | |
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650 | 4 | |a organ transplantation | |
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700 | 1 | |a Cho, Ara |e verfasserin |4 aut | |
700 | 1 | |a Weijler, Anna Marianne |e verfasserin |4 aut | |
700 | 1 | |a Muckenhuber, Moritz |e verfasserin |4 aut | |
700 | 1 | |a Hofmann, Amun Georg |e verfasserin |4 aut | |
700 | 1 | |a Wahrmann, Markus |e verfasserin |4 aut | |
700 | 1 | |a Heinzel, Andreas |e verfasserin |4 aut | |
700 | 1 | |a Linhart, Birgit |e verfasserin |4 aut | |
700 | 1 | |a Gattinger, Pia |e verfasserin |4 aut | |
700 | 1 | |a Valenta, Rudolf |e verfasserin |4 aut | |
700 | 1 | |a Berlakovich, Gabriela |e verfasserin |4 aut | |
700 | 1 | |a Zuckermann, Andreas |e verfasserin |4 aut | |
700 | 1 | |a Jaksch, Peter |e verfasserin |4 aut | |
700 | 1 | |a Oberbauer, Rainer |e verfasserin |4 aut | |
700 | 1 | |a Wekerle, Thomas |e verfasserin |4 aut | |
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