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Article ; Online: Clinical Pig Heart Xenotransplantation-Where Do We Go From Here?

Cooper, David K C / Cozzi, Emanuele

Transplant international : official journal of the European Society for Organ Transplantation

2024 Volume 37, Page(s) 12592

MeSH term(s)	Animals ; Swine ; Transplantation, Heterologous ; Animals, Genetically Modified ; Graft Rejection ; Heart ; Thorax
Language	English
Publishing date	2024-02-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	639435-8
ISSN	1432-2277 ; 0934-0874
ISSN (online)	1432-2277
ISSN	0934-0874
DOI	10.3389/ti.2024.12592
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Article ; Conference proceedings: Proceedings of the joint meeting of the International Pancreas and Islet Transplant Association and the International Xenotransplantation Association, IPITA - IXA

Cozzi, Emanuele

Transplantation proceedings 42 ,6, S. 1999 - 2263 : Ill., graph. Darst.

October 12 - 17, 2009, Venice, Italy

2010

Institution	International Pancreas and Islet Transplant Association International Xenotransplantation Association
Author's details	guest ed. Emanuele Cozzi
Collection	Transplantation proceedings
Language	English
Publishing place	New York, NY
Publishing country	United States
Document type	Article ; Conference proceedings
HBZ-ID	HT016693252
Database	Catalogue ZB MED Medicine, Health

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Zs A 835 -42-

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Article ; Online: Current challenges in xenotransplantation.

Vadori, Marta / Cozzi, Emanuele

Current opinion in organ transplantation

2024

Abstract: Purpose of review: In recent years, the xenotransplantation science has advanced tremendously, with significant strides in both preclinical and clinical research. This review intends to describe the latest cutting-edge progress in knowledge and ... ...

Abstract	Purpose of review: In recent years, the xenotransplantation science has advanced tremendously, with significant strides in both preclinical and clinical research. This review intends to describe the latest cutting-edge progress in knowledge and methodologies developed to overcome potential obstacles that may preclude the translation and successful application of clinical xenotransplantation. Recent findings: Preclinical studies have demonstrated that it is now possible to extend beyond two years survival of primate recipients of life saving xenografts. This has been accomplished thanks to the utilization of genetic engineering methodologies that have allowed the generation of specifically designed gene-edited pigs, a careful donor and recipient selection, and appropriate immunosuppressive strategies.In this light, the compassionate use of genetically modified pig hearts has been authorized in two human recipients and xenotransplants have also been achieved in human decedents. Although encouraging the preliminary results suggest that several challenges have yet to be fully addressed for a successful clinical translation of xenotransplantation. These challenges include immunologic, physiologic and biosafety aspects. Summary: Recent progress has paved the way for the initial compassionate use of pig organs in humans and sets the scene for a wider application of clinical xenotransplantation.
Language	English
Publishing date	2024-03-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	1390429-2
ISSN	1531-7013 ; 1087-2418
ISSN (online)	1531-7013
ISSN	1087-2418
DOI	10.1097/MOT.0000000000001146
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Zs.A 5609: Show issues

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Article ; Online: Challenging the Role of Diet-Induced Anti-Neu5Gc Antibodies in Human Pathologies.

Soulillou, Jean-Paul / Cozzi, Emanuele / Bach, Jean-Marie

Frontiers in immunology

2020 Volume 11, Page(s) 834

MeSH term(s)	Antibodies/immunology ; Antigens/immunology ; Asthma/immunology ; Diet/adverse effects ; Humans ; Infertility/immunology ; Multiple Sclerosis/immunology ; Neoplasms/immunology ; Neuraminic Acids/administration & dosage ; Neuraminic Acids/immunology ; Vascular Diseases/immunology
Chemical Substances	Antibodies ; Antigens ; Neuraminic Acids ; N-glycolylneuraminic acid (1113-83-3)
Language	English
Publishing date	2020-06-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.00834
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Article ; Online: C1q-binding donor-specific antibody assays help define risk and prognosis in antibody-mediated rejection.

Cozzi, Emanuele / Biancone, Luigi

Kidney international

2018 Volume 94, Issue 4, Page(s) 657–659

Abstract: Antibody-mediated rejection represents the first cause of graft loss in renal transplant recipients, and it is imperative to identify appropriate tools to enable risk stratification of such patients. Lately, the usefulness of measuring complement-binding ...

Abstract	Antibody-mediated rejection represents the first cause of graft loss in renal transplant recipients, and it is imperative to identify appropriate tools to enable risk stratification of such patients. Lately, the usefulness of measuring complement-binding anti-human leukocyte antigen (HLA) donor-specific antibodies (DSAs) in renal transplantation has been intensely debated. While the jury is still out, recent data suggest that monitoring complement-binding DSAs may help to recognize high-risk patients and possibly trigger more effective interventions in selected patients.
MeSH term(s)	Graft Rejection ; Graft Survival ; HLA Antigens ; Humans ; Kidney Transplantation ; Prognosis ; Tissue Donors
Chemical Substances	HLA Antigens
Language	English
Publishing date	2018-09-19
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	120573-0
ISSN	1523-1755 ; 0085-2538
ISSN (online)	1523-1755
ISSN	0085-2538
DOI	10.1016/j.kint.2018.06.032
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Zs.A 797: Show issues

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Article ; Online: European Consensus on the Management of Sensitized Kidney Transplant Recipients: A Delphi Study.

Furian, Lucrezia / Bestard, Oriol / Budde, Klemens / Cozzi, Emanuele / Diekmann, Fritz / Mamode, Nizam / Naesens, Maarten / Pengel, Liset H M / Schwartz Sorensen, Soren / Vistoli, Fabio / Thaunat, Olivier

Transplant international : official journal of the European Society for Organ Transplantation

2024 Volume 37, Page(s) 12475

Abstract: An increasing number of sensitized patients awaiting transplantation face limited options, leading to fatalities during dialysis and higher costs. The absence of established evidence highlights the need for collaborative consensus. Donor-specific ... ...

Abstract	An increasing number of sensitized patients awaiting transplantation face limited options, leading to fatalities during dialysis and higher costs. The absence of established evidence highlights the need for collaborative consensus. Donor-specific antibodies (DSA)-triggered antibody-mediated rejection (AMR) significantly contributes to kidney graft failure, especially in sensitized patients. The European Society for Organ Transplantation (ESOT) launched the ENGAGE initiative, categorizing sensitized candidates by AMR risk to improve patient care. A systematic review assessed induction and maintenance regimens as well as antibody removal strategies, with statements subjected to the Delphi methodology. A Likert-scale survey was distributed to 53 European experts (Nephrologists, Transplant surgeons and Immunologists) with experience in kidney transplant recipient care. A rate ≥75% with the same answer was considered consensus. Consensus was achieved in 95.3% of statements. While most recommendations aligned, two statements related to complement inhibitors for AMR prophylaxis lacked consensus. The ENGAGE consensus presents contemporary recommendations for desensitization and immunomodulation strategies, grounded in predefined risk categories. The adoption of tailored, patient-specific measures is anticipated to streamline the care of sensitized recipients undergoing renal allografts. While this approach holds the promise of enhancing transplant accessibility and fostering long-term success in transplantation outcomes, its efficacy will need to be assessed through dedicated studies.
MeSH term(s)	Humans ; Kidney Transplantation ; Delphi Technique ; Graft Rejection/prevention & control ; Graft Rejection/immunology ; Consensus ; Europe ; Isoantibodies/immunology ; Transplant Recipients
Chemical Substances	Isoantibodies
Language	English
Publishing date	2024-04-11
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Editorial
ZDB-ID	639435-8
ISSN	1432-2277 ; 0934-0874
ISSN (online)	1432-2277
ISSN	0934-0874
DOI	10.3389/ti.2024.12475
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Zs.A 2358: Show issues

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Article ; Online: Can we extrapolate from a

Soulillou, Jean-Paul / Cozzi, Emanuele / Galli, Cesare / Bach, Jean-Marie

Proceedings of the National Academy of Sciences of the United States of America

2020 Volume 117, Issue 4, Page(s) 1845–1846

MeSH term(s)	Animals ; Atherosclerosis ; Humans ; Mice ; Mixed Function Oxygenases ; Receptors, LDL
Chemical Substances	Receptors, LDL ; Mixed Function Oxygenases (EC 1.-) ; CMPacetylneuraminate monooxygenase (EC 1.14.18.2)
Language	English
Publishing date	2020-01-21
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1915658117
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Zs.A 1148: Show issues

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Article ; Online: First-in-human Study With LIS1, a Next-generation Porcine Low Immunogenicity Antilymphocyte Immunoglobulin in Kidney Transplantation.

Viklicky, Ondrej / Slatinska, Janka / Janousek, Libor / Rousse, Juliette / Royer, Pierre-Joseph / Toutain, Pierre-Louis / Cozzi, Emanuele / Galli, Cesare / Evanno, Gwenaelle / Duvaux, Odile / Bach, Jean-Marie / Soulillou, Jean-Paul / Giral, Magali / Vanhove, Bernard / Blancho, Gilles

Transplantation

2024

Abstract: Background: Polyclonal rabbit antithymocyte globulins (ATGs) are commonly used in organ transplantation as induction. Anti-N-glycolylneuraminic acid carbohydrate antibodies which develop in response to rabbit carbohydrate antigens might lead to unwanted ...

Abstract	Background: Polyclonal rabbit antithymocyte globulins (ATGs) are commonly used in organ transplantation as induction. Anti-N-glycolylneuraminic acid carbohydrate antibodies which develop in response to rabbit carbohydrate antigens might lead to unwanted systemic inflammation. LIS1, the first new generation of antilymphocyte globulins (ALGs) derived from double knockout swine, lacking carbohydrate xenoantigens was already tested in nonhuman primates and rodent models. Methods: This open-label, single-site, dose escalation, first-in-human, phase 1 study evaluated the safety, T cell depletion, pharmacokinetics, and pharmacodynamics of LIS1. In an ascending dose cohort (n = 5), a primary kidney transplant recipient at low immunologic risk (panel reactive antibody [PRA] < 20%), received LIS1 for 5 d at either 0.6, 1, 3, 6, or 8 mg/kg. After each patient completed treatment, the data safety monitoring board approved respective dose escalation. In the therapeutic dose cohort (n = 5) in patients with PRA <50% without donor specific antibodies, 2 patients received 8 mg/kg and 3 patients 10 mg/kg. Results: CD3+ T cell depletion <100/mm3 at day 2 was observed in all patients who received 6, 8, and 10 mg/kg of LIS1. The terminal half-life of LIS1 was 33.7 d with linearity in its disposition. Lymphocyte repopulation was fast and pretransplant lymphocyte subpopulation counts recovered within 2-4 wk. LIS1 was well tolerated, neither cytokine release syndrome nor severe thrombocytopenia or leukopenia were noticed. Antibodies to LIS1 were not detected. Conclusions: In this first-in-human trial, genome-edited swine-derived polyclonal LIS1 ALG was well tolerated, did not elicit antidrug antibodies, and caused time-limited T cell depletion in low- and medium-risk kidney transplant recipients.
Language	English
Publishing date	2024-02-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	208424-7
ISSN	1534-6080 ; 0041-1337
ISSN (online)	1534-6080
ISSN	0041-1337
DOI	10.1097/TP.0000000000004967
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Zs.A 488: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Association of Angiotensin II Receptor Type 1 and Endothelin-1 Receptor Type A Agonistic Autoantibodies With Adverse Remodeling and Cardiovascular Events After Acute Myocardial Infarction.

Tona, Francesco / Civieri, Giovanni / Vadori, Marta / Masiero, Giulia / Iop, Laura / Marra, Martina Perazzolo / Perin, Valentina / Cuciz, Elisa / Cecere, Annagrazia / Bernava, Giacomo / Tansella, Donatella / Naumova, Nataliia / Grewal, Simran / Cozzi, Emanuele / Iliceto, Sabino

Journal of the American Heart Association

2024 Volume 13, Issue 4, Page(s) e032672

Abstract: Background: The left ventricular remodeling (LVR) process has limited the effectiveness of therapies after myocardial infarction. The relationship between autoantibodies activating AT1R-AAs (angiotensin II receptor type 1-AAs) and ETAR-AAs ( ... ...

Abstract	Background: The left ventricular remodeling (LVR) process has limited the effectiveness of therapies after myocardial infarction. The relationship between autoantibodies activating AT1R-AAs (angiotensin II receptor type 1-AAs) and ETAR-AAs (autoantibodies activating endothelin-1 receptor type A) with myocardial infarction has been described. Among patients with ST-segment-elevation myocardial infarction, we investigated the relationship between these autoantibodies with LVR and subsequent major adverse cardiac events. Methods and results: In this prospective observational study, we included 131 patients with ST-segment-elevation myocardial infarction (61±11 years of age, 112 men) treated with primary percutaneous coronary intervention. Within 48 hours of admission, 2-dimensional transthoracic echocardiography was performed, and blood samples were obtained. The seropositive threshold for AT1R-AAs and ETAR-AAs was >10 U/mL. Patients were followed up at 6 months, when repeat transthoracic echocardiography was performed. The primary end points were LVR, defined as a 20% increase in left ventricular end-diastolic volume index, and major adverse cardiac event occurrence at follow-up, defined as cardiac death, nonfatal re-myocardial infarction, and hospitalization for heart failure. Forty-one (31%) patients experienced LVR. The prevalence of AT1R-AAs and ETAR-AAs seropositivity was higher in patients with versus without LVR (39% versus 11%, Conclusions: AT1R-AAs and ETAR-AAs are associated with LVR in patients with ST-segment-elevation myocardial infarction. AT1R-AAs are also significantly associated with recurrent major adverse cardiac events. These initial observations may set the stage for a better pathophysiological understanding of the mechanisms contributing to LVR and ST-segment-elevation myocardial infarction prognosis.
MeSH term(s)	Male ; Humans ; Aged, 80 and over ; Receptor, Endothelin A ; Myocardial Infarction/therapy ; Prognosis ; Echocardiography ; ST Elevation Myocardial Infarction/diagnostic imaging ; ST Elevation Myocardial Infarction/therapy ; ST Elevation Myocardial Infarction/complications ; Percutaneous Coronary Intervention ; Receptors, Angiotensin ; Ventricular Remodeling/physiology ; Ventricular Function, Left/physiology
Chemical Substances	Receptor, Endothelin A ; Receptors, Angiotensin
Language	English
Publishing date	2024-02-13
Publishing country	England
Document type	Observational Study ; Journal Article
ZDB-ID	2653953-6
ISSN	2047-9980 ; 2047-9980
ISSN (online)	2047-9980
ISSN	2047-9980
DOI	10.1161/JAHA.123.032672
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Article ; Online: Spontaneous coronary artery dissection in women with acute myocardial infarction: is there a new role for autoimmunity?

Civieri, Giovanni / Vadori, Marta / Masiero, Giulia / Iop, Laura / Tansella, Donatella / Pergola, Valeria / Cozzi, Emanuele / Iliceto, Sabino / Tona, Francesco

European heart journal. Acute cardiovascular care

2023 Volume 12, Issue 12, Page(s) 856–861

Abstract: Aims: Spontaneous coronary artery dissection (SCAD) is an uncommon cause of acute myocardial infarction in women and has an unclear pathophysiology. Autoantibodies (AAs) targeting angiotensin-II receptor type 1 (AT1R) and endothelin-1 receptor type A ( ... ...

Abstract	Aims: Spontaneous coronary artery dissection (SCAD) is an uncommon cause of acute myocardial infarction in women and has an unclear pathophysiology. Autoantibodies (AAs) targeting angiotensin-II receptor type 1 (AT1R) and endothelin-1 receptor type A (ETAR) have known detrimental effects on endothelial function. We investigated the prevalence of these AAs in SCAD-affected female patients. Methods and results: Female patients diagnosed at coronary angiography with myocardial infarction and SCAD were consecutively enrolled. Autoantibodies targeting angiotensin-II receptor type 1 and ETAR-AA titres and seropositivity prevalence were compared between SCAD patients, ST-elevation myocardial infarction (STEMI) patients, and healthy women. Ten women with SCAD and 20 age-matched controls (10 women with STEMI and 10 healthy women) were included. Six out of 10 (60%) women with myocardial infarction and SCAD were seropositive for AT1R-AAs and ETAR-AAs. In contrast, only one (10%) healthy woman and one (10%) STEMI patient were seropositive for AT1R-AAs (P = 0.03 and P = 0.03, respectively). One STEMI patient was seropositive for ETAR-AAs, while none of the healthy women was found to be seropositive (P = 0.03 and P = 0.01, respectively). The median AA titre was significantly higher in SCAD patients than in healthy women (P = 0.01 for AT1R-AAs; P = 0.02 for ETAR-AAs) and STEMI patients (P < 0.001 for AT1R-AAs; P = 0.002 for ETAR-AAs). Conclusion: Autoantibodies targeting angiotensin-II receptor type 1 and ETAR-AA seropositivity is significantly higher in SCAD women with myocardial infarction than in healthy women or female patients with STEMI. Our findings, corroborated by previous data in the literature and biological plausibility, suggest a possible role for AT1R-AAs and ETAR-AAs in the pathophysiology of SCAD in women with acute myocardial infarction and should warrant further studies with larger sample sizes.
MeSH term(s)	Humans ; Female ; Male ; ST Elevation Myocardial Infarction/complications ; ST Elevation Myocardial Infarction/diagnosis ; Autoimmunity ; Coronary Vessels/diagnostic imaging ; Retrospective Studies ; Vascular Diseases/diagnosis ; Myocardial Infarction/complications ; Coronary Angiography ; Autoantibodies ; Coronary Vessel Anomalies/complications ; Coronary Vessel Anomalies/diagnosis ; Coronary Vessel Anomalies/epidemiology ; Angiotensins
Chemical Substances	Autoantibodies ; Angiotensins
Language	English
Publishing date	2023-06-30
Publishing country	England
Document type	Journal Article
ZDB-ID	2663340-1
ISSN	2048-8734 ; 2048-8726
ISSN (online)	2048-8734
ISSN	2048-8726
DOI	10.1093/ehjacc/zuad070
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