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

Frontiers in Immunology

Immunology

Hans Eiskjær¹  Marie Skougaard²  Pernille Koefoed-Nielsen²  Steen Bærentzen³ 

[1] Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark;Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark;Department of Pathology, Aarhus University Hospital, Aarhus, Denmark;

关键词: heart transplantation;    mixed rejection;    HLA;    epitope;    antibody;    case report;   

DOI  :  10.3389/fimmu.2023.1207373

 received in 2023-04-17, accepted in 2023-07-18,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

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Copyright © 2023 Skougaard, Bærentzen, Eiskjær and Koefoed-Nielsen