• Media type: E-Article
  • Title: Prospective assessment of pre-existing and de novo anti-HLA IgE in kidney, liver, lung and heart transplantation
  • Contributor: Mucha, Jasmin; Cho, Ara; Weijler, Anna Marianne; Muckenhuber, Moritz; Hofmann, Amun Georg; Wahrmann, Markus; Heinzel, Andreas; Linhart, Birgit; Gattinger, Pia; Valenta, Rudolf; Berlakovich, Gabriela; Zuckermann, Andreas; Jaksch, Peter; Oberbauer, Rainer; Wekerle, Thomas
  • imprint: Frontiers Media SA, 2023
  • Published in: Frontiers in Immunology
  • Language: Not determined
  • DOI: 10.3389/fimmu.2023.1179036
  • ISSN: 1664-3224
  • Keywords: Immunology ; Immunology and Allergy
  • Origination:
  • Footnote:
  • Description: <jats:sec><jats:title>Introduction</jats:title><jats:p>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 <jats:italic>de novo</jats:italic> anti-HLA IgE antibodies in a cohort of 105 solid organ transplant recipients.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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 <jats:italic>in vitro</jats:italic> mediator release assay. Antibodies of the IgG1-4 subclasses and Th1 and Th2 cytokines were measured in anti-HLA IgE positive patients.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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 <jats:italic>de novo</jats:italic> anti-HLA IgE antibodies (1.7% of kidney recipients and 4.4% of non-renal recipients), whereas no <jats:italic>de novo</jats:italic> 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 <jats:italic>in vitro</jats:italic>, demonstrating functionality of anti-HLA IgE.</jats:p></jats:sec><jats:sec><jats:title>Discussion</jats:title><jats:p>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.</jats:p></jats:sec>
  • Access State: Open Access