Marie Carbonnel, Maxime Petit, Nadine Tarantino, Veronique Morin, Aurélien Corneau, Morgan Tourne, Justine Gueguan, Johann Mölne, Randa Akouri, Verena Broecker, Angélique Vinit, Catherine Racowsky, Mats Brännström, Jean-Marc Ayoubi, Vincent Vieillard
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引用次数: 0
Abstract
Background: Uterus transplantation (UTx) is an emerging therapy for women with uterine infertility. However, critical questions remain with this procedure including the mechanisms involved in graft rejection.
Methods: In this study, we analyzed the immune profile of ectocervical biopsies from 5 patients after UTx before and during their first episode of rejection using RNA sequencing, quantitative polymerase chain reaction, and imaging mass cytometry.
Results: We identified 530 upregulated and 207 downregulated genes associated with graft rejection. Enrichment databases revealed abnormalities of skin-associated genes and the immune system, in particular activation of T and B lymphocytes, and macrophages. Imaging mass cytometry confirmed these observations; in cervical biopsies of 3 women, rejection was associated with the presence of B-cell structures linked to tertiary lymphoid structures, and 2 biopsies from 1 woman with severe rejection episodes and poor prognosis of graft function (repeated miscarriage and implantation failures) were associated with an accumulation of HLA-DR- macrophages, producing granzyme B at the surface of the epithelium.
Conclusions: We showed that rejection of a UTx graft was associated with major alterations of immune markers including the involvement of tertiary lymphoid structures, the most organized of which may be a sign of chronic rejection, and with an increase in HLA-DR- macrophages expressing granzyme B in the case of grade 3 rejection episodes according Mölne's classification. We identified potential emerging biomarkers to predict or diagnose graft rejection (Keratin 1 granzyme B, IL1β). These findings could lead to development of improved strategies for the identification, prevention, and/or treatment of uterus graft rejection.
期刊介绍：
The official journal of The Transplantation Society, and the International Liver Transplantation Society, Transplantation is published monthly and is the most cited and influential journal in the field, with more than 25,000 citations per year.
Transplantation has been the trusted source for extensive and timely coverage of the most important advances in transplantation for over 50 years. The Editors and Editorial Board are an international group of research and clinical leaders that includes many pioneers of the field, representing a diverse range of areas of expertise. This capable editorial team provides thoughtful and thorough peer review, and delivers rapid, careful and insightful editorial evaluation of all manuscripts submitted to the journal.
Transplantation is committed to rapid review and publication. The journal remains competitive with a time to first decision of fewer than 21 days. Transplantation was the first in the field to offer CME credit to its peer reviewers for reviews completed.
The journal publishes original research articles in original clinical science and original basic science. Short reports bring attention to research at the forefront of the field. Other areas covered include cell therapy and islet transplantation, immunobiology and genomics, and xenotransplantation.
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