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Eosinophilic infiltration as the initial trace of acute mixed cellular and antibody mediated rejection in a heart transplant patient with concomitant immense epitope-associated HLA-antibody production: a case report
Acute mixed cellular and antibody-mediated rejection (MR) has an estimated prevalence of 7.8%. However, knowledge of MR immune pathogenesis in cardiac graft rejection remains sparse. We report a case of acute MR in a heart transplant patient with a mutation in the MYH7 gene encoding the protein β-my...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10516220/ https://www.ncbi.nlm.nih.gov/pubmed/37744343 http://dx.doi.org/10.3389/fimmu.2023.1207373 |
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author | Skougaard, Marie Bærentzen, Steen Eiskjær, Hans Koefoed-Nielsen, Pernille |
author_facet | Skougaard, Marie Bærentzen, Steen Eiskjær, Hans Koefoed-Nielsen, Pernille |
author_sort | Skougaard, Marie |
collection | PubMed |
description | Acute mixed cellular and antibody-mediated rejection (MR) has an estimated prevalence of 7.8%. However, knowledge of MR immune pathogenesis in cardiac graft rejection remains sparse. We report a case of acute MR in a heart transplant patient with a mutation in the MYH7 gene encoding the protein β-myosin heavy chain, resulting in familial hypertrophic cardiomyopathy. The patient presented with substantial eosinophilic infiltration and extensive production of Human Leukocyte Antigen (HLA)-antibodies associated with shared epitopes. Eosinophilic infiltration in the endo- and myocardium was diagnosed in routine post-transplant biopsies stained with hematoxylin-eosin on day 6 after transplantation. On day 27, the patient presented with dyspnea, weight gain, increased pro-brain natriuretic peptide, and was hospitalized due to suspected acute rejection. Endomyocardial biopsies showed eosinophils in endo- and myocardium with additional lymphocytes and hyperplastic endothelium. Immunohistochemistry, including CD31/CD68 double stain confirmed endothelium-associated macrophages in capillaries and severe C4d positivity in the capillaries and endocardial endothelium. Lymphocytes were identified as primarily CD45+/CD3+ T cells with a concomitant few CD45+/CD20+ B cells. HLA-antibody analysis demonstrated a significant increase in 13 HLA-antibodies present in pre-transplant-serum, of which anti-B7 was donor-specific, and 23 strong de-novo HLA-class I antibodies of which anti-B62 was donor-specific. 72% of HLA-antibodies, including the two donor-specific antibodies, shared the same HLA antigen epitope; 43P+69A or 163L+167W. This is a case reporting both HLA-antibody and pathohistological data indicating the need for better understanding of interactions between cellular and antibody-mediated immune response mechanisms in graft rejection, and the significance of pre-transplant donor-specific antibodies during immunological pre-transplant risk assessment. |
format | Online Article Text |
id | pubmed-10516220 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-105162202023-09-23 Eosinophilic infiltration as the initial trace of acute mixed cellular and antibody mediated rejection in a heart transplant patient with concomitant immense epitope-associated HLA-antibody production: a case report Skougaard, Marie Bærentzen, Steen Eiskjær, Hans Koefoed-Nielsen, Pernille Front Immunol Immunology Acute mixed cellular and antibody-mediated rejection (MR) has an estimated prevalence of 7.8%. However, knowledge of MR immune pathogenesis in cardiac graft rejection remains sparse. We report a case of acute MR in a heart transplant patient with a mutation in the MYH7 gene encoding the protein β-myosin heavy chain, resulting in familial hypertrophic cardiomyopathy. The patient presented with substantial eosinophilic infiltration and extensive production of Human Leukocyte Antigen (HLA)-antibodies associated with shared epitopes. Eosinophilic infiltration in the endo- and myocardium was diagnosed in routine post-transplant biopsies stained with hematoxylin-eosin on day 6 after transplantation. On day 27, the patient presented with dyspnea, weight gain, increased pro-brain natriuretic peptide, and was hospitalized due to suspected acute rejection. Endomyocardial biopsies showed eosinophils in endo- and myocardium with additional lymphocytes and hyperplastic endothelium. Immunohistochemistry, including CD31/CD68 double stain confirmed endothelium-associated macrophages in capillaries and severe C4d positivity in the capillaries and endocardial endothelium. Lymphocytes were identified as primarily CD45+/CD3+ T cells with a concomitant few CD45+/CD20+ B cells. HLA-antibody analysis demonstrated a significant increase in 13 HLA-antibodies present in pre-transplant-serum, of which anti-B7 was donor-specific, and 23 strong de-novo HLA-class I antibodies of which anti-B62 was donor-specific. 72% of HLA-antibodies, including the two donor-specific antibodies, shared the same HLA antigen epitope; 43P+69A or 163L+167W. This is a case reporting both HLA-antibody and pathohistological data indicating the need for better understanding of interactions between cellular and antibody-mediated immune response mechanisms in graft rejection, and the significance of pre-transplant donor-specific antibodies during immunological pre-transplant risk assessment. Frontiers Media S.A. 2023-09-08 /pmc/articles/PMC10516220/ /pubmed/37744343 http://dx.doi.org/10.3389/fimmu.2023.1207373 Text en Copyright © 2023 Skougaard, Bærentzen, Eiskjær and Koefoed-Nielsen https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Skougaard, Marie Bærentzen, Steen Eiskjær, Hans Koefoed-Nielsen, Pernille Eosinophilic infiltration as the initial trace of acute mixed cellular and antibody mediated rejection in a heart transplant patient with concomitant immense epitope-associated HLA-antibody production: a case report |
title | Eosinophilic infiltration as the initial trace of acute mixed cellular and antibody mediated rejection in a heart transplant patient with concomitant immense epitope-associated HLA-antibody production: a case report |
title_full | Eosinophilic infiltration as the initial trace of acute mixed cellular and antibody mediated rejection in a heart transplant patient with concomitant immense epitope-associated HLA-antibody production: a case report |
title_fullStr | Eosinophilic infiltration as the initial trace of acute mixed cellular and antibody mediated rejection in a heart transplant patient with concomitant immense epitope-associated HLA-antibody production: a case report |
title_full_unstemmed | Eosinophilic infiltration as the initial trace of acute mixed cellular and antibody mediated rejection in a heart transplant patient with concomitant immense epitope-associated HLA-antibody production: a case report |
title_short | Eosinophilic infiltration as the initial trace of acute mixed cellular and antibody mediated rejection in a heart transplant patient with concomitant immense epitope-associated HLA-antibody production: a case report |
title_sort | eosinophilic infiltration as the initial trace of acute mixed cellular and antibody mediated rejection in a heart transplant patient with concomitant immense epitope-associated hla-antibody production: a case report |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10516220/ https://www.ncbi.nlm.nih.gov/pubmed/37744343 http://dx.doi.org/10.3389/fimmu.2023.1207373 |
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