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Induction with anti-T-lymphocyte globulins and human immunoglobulins: A strategy for hyperimmunized liver transplant patients
Nada EL-Domiaty, Audrey Coilly, Mylene Sebagh, Jean-Luc Taupin, Wafaa Ibrahim, Sophie-Caroline Sacleux, Philippe Ichai, Lea Duhaut, Gabriella Pittau, Oriana Ciacio, Chady Salloum, Antonio Sa-Cunha, Daniel Azoulay, Cyrille Feray, Daniel Cherqui, Gamal Shiha, Didier Samuel, Faouzi Saliba
Nada EL-Domiaty, Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo 00202, Egypt
Nada EL-Domiaty, Audrey Coilly, Mylene Sebagh, Sophie-Caroline Sacleux, Philippe Ichai, Lea Duhaut, Gabriella Pittau, Oriana Ciacio, Chady Salloum, Antonio Sa-Cunha, Daniel Azoulay, Cyrille Feray, Daniel Cherqui, Didier Samuel, Faouzi Saliba, Hepato-Biliary Centre, Villejuif-France, INSERM UMR 1193 & Université Paris Saclay, AP-HP Hôpital Paul Brousse, Paris 94800, France
Jean-Luc Taupin, Department of Immunology and Histocompatibility, AP-HP Groupe Hospitalier St-Louis Lariboisière, Paris 94800, France
Wafaa Ibrahim, Department of Statistics, Faculty of Economics and Political Science, Cairo University, Cairo 12613, Egypt
Gamal Shiha, Department of Gastroenterology and Hepatology Unit, Department of Internal Medicine, Faculty of Medicine, Mansoura 11001, Egypt
Author contributions: EL-Domiaty N participated in research design, acquisition of data, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript, statistical analysis; Ibrahim W participated in analysis and interpretation of data, statistical analysis; Sebagh M viewed and approved all the pathology and critical revision of the manuscript; Taupin JL participated in measurements and validation of immunological tests and critical revision of the manuscript; Saliba F participated in research design, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript; Coilly A, Sacleux SC, Duhaut L, Ichai P, Pittau G, Ciacio O, Salloum C, Sa-Cunah A, Azoulay D, Feray C, Cherqui D, Shiha G, and Samuel D participated in critical revision and approval of the manuscript.
Institutional review board statement: Data were retrospectively collected from charts and electronic databases after approval by the local institutional review board, in accordance with the International Guidelines for Ethical Review of Epidemiological Studies and principles of the Declaration of Helsinki.
Informed consent statement: The authors declare that the study consisted of a retrospective study to assess whether induction therapy with rabbit anti-T lymphocyte globulin and high-dose intravenous immunoglobulin reduces acute T-cell mediated rejection, antibody-mediated rejection, and graft loss in hyperimmunized patients and was conducted in accordance to the Declaration of Helsinki.
Conflict-of-interest statement: All authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement – checklist of items, and the manuscript was prepared and revised according to the STROBE Statement – checklist of items.
Data sharing statement: No additional data is available.
Corresponding author: Faouzi Saliba, PhD, Professor, Hepato-Biliary Centre, Villejuif-France, INSERM UMR 1193 & Université Paris Saclay, AP-HP Hôpital Paul Brousse, 12, Avenue Paul Vaillant Couturier, Paris 94800, France.
faouzi.saliba@aphp.fr
Received: October 14, 2025
Revised: November 7, 2025
Accepted: January 5, 2026
Published online: March 27, 2026
Processing time: 166 Days and 13.8 Hours
BACKGROUND
Liver transplantation (LT) in hyperimmunized recipients with pre-formed donor-specific antibodies (pDSA) or a positive crossmatch (CM) presents a significant immunological graft challenge.
AIM
To assess whether induction therapy with rabbit anti-T lymphocyte globulin (rATLG) and high-dose intravenous immunoglobulin (IVIG) reduces acute T-cell mediated rejection (TCMR), acute antibody-mediated rejection (aAMR), and graft loss in these patients.
METHODS
This retrospective case-control study, conducted between 2016 and 2022, compared the outcomes of two groups of LT recipients: Forty-six hyperimmunized patients (high-risk, pDSA and/or CM positive at time of LT) were matched with 46 non-immunized (low-risk) recipients. High-risk patients received anti-T lymphocyte globulin/IVIG induction therapy whereas the low-risk patients did not. Patient and graft survival were compared using Kaplan-Meier survival analysis.
RESULTS
The incidence of biopsy-proven TCMR was numerically lower in the high-risk group (19.6%) compared to the low-risk group (26.1%), with all cases classified as Banff mild or moderate. Of these, clinically significant rejections requiring treatment occurred in 10.9% of high-risk and 8.7% of low-risk recipients. A subset of the high-risk group (n = 4, 8.7%) developed aAMR vs none in the low-risk group. The one-year (high-risk: 83.6%, low-risk: 95.6%) and three-year (high-risk: 78.0%, low-risk: 91.2%) survival rates were comparable between the two groups (log-rank P = 0.051). Notably, no grafts were lost due to rejection in either group, and no adverse events were linked to the induction therapy used in the high-risk group.
CONCLUSION
Short course of rATLG and IVIG induction therapy can be a valuable strategy for mitigating early immunological risks in hyperimmunized recipients, leading to comparable outcomes to non-immunized patients.
Core Tip: For hyperimmunized liver transplant recipients with high mean fluorescence intensity titer of pre-formed donor-specific antibodies and/or donor/recipient positive crossmatch, early induction with a short course of rabbit anti-T-lymphocyte globulins combined with high-dose intravenous immune-globulins can be a valuable strategy for mitigating early immunological risks (T-cell mediated rejection, acute antibody-mediated rejection severity and graft loss). If allograft dysfunction is suspected, closer serial donor-specific antibodies monitoring and early liver biopsy should be considered for timely diagnosis and management of antibody-mediated injury.
