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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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Article ; Online: Polyclonal antibodies selectively inhibit tumor growth and invasion and synergize with immune checkpoint inhibitors.

Ciron, Carine / Morice, Pierre / Rousse, Juliette / Roy, Patrice / Royer, Pierre-Joseph / Gauthier, Olivier / Brouard, Sophie / Duvaux, Odile / Bassissi, Firas / Vanhove, Bernard

JCI insight

2024 Volume 9, Issue 3

Abstract: Heterologous polyclonal antibodies (pAb) were shown to possess oncolytic properties a century ago with reported clinical responses. More recent preclinical models confirmed pAb efficacy, though their ability to tackle complex target antigens reduces ... ...

Abstract	Heterologous polyclonal antibodies (pAb) were shown to possess oncolytic properties a century ago with reported clinical responses. More recent preclinical models confirmed pAb efficacy, though their ability to tackle complex target antigens reduces susceptibility to tumor escape. Owing to the recent availability of glyco-humanized pAb (GH-pAb) with acceptable clinical toxicology profile, we revisited use of pAb in oncology and highlighted their therapeutic potential against multiple cancer types. Murine antitumor pAb were generated after repeated immunization of rabbits with murine tumor cell lines from hepatocarcinoma, melanoma, and colorectal cancers. Antitumor pAb recognized and showed cytotoxicity against their targets without cross-reactivity with healthy tissues. In vivo, pAb are effective alone; moreover, these pAb synergize with immune checkpoint inhibitors like anti-PD-L1 in several cancer models. They elicited an antitumor host immune response and prevented metastases. The anticancer activity of pAb was also confirmed in xenografted NMRI nude mice using GH-pAb produced by repeated immunization of pigs with human tumor cell lines. In conclusion, the availability of bioengineered GH-pAb allows for revisiting of passive immunotherapy with oncolytic pAb to fight against solid tumor and cancer metastasis.
MeSH term(s)	Humans ; Rabbits ; Animals ; Mice ; Swine ; Immune Checkpoint Inhibitors ; Mice, Nude ; Immunization ; Melanoma/therapy ; Cell Line, Tumor ; Antibodies, Neoplasm/pharmacology
Chemical Substances	Immune Checkpoint Inhibitors ; Antibodies, Neoplasm
Language	English
Publishing date	2024-02-08
Publishing country	United States
Document type	Journal Article
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.166231
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Article ; Online: XAV-19 a Glyco-Humanized polyclonal antibody targeting SARS-CoV-2 accelerates the recovery of mild to moderate COVID-19 patients and keeps its neutralizing activity against Omicron and its subvariants

Poulakou, Garyfallia / Royer, Pierre-Joseph / Evgeniev, Nikolai / Evanno, Gwénaëlle / Shneiker, Françoise / Vanhove, Bernard / Duvaux, Odile / Marot, Stéphane / Calvez, Vincent

medRxiv

Abstract: Background: XAV-19 is a glyco-humanized swine polyclonal antibody targeting SARS-CoV-2. The safety and clinical efficacy of XAV-19 was investigated in patients with a WHO score of 2 to 4 in the WHO 7-point ordinal scale. The activity of XAV-19 against ... ...

Abstract	Background: XAV-19 is a glyco-humanized swine polyclonal antibody targeting SARS-CoV-2. The safety and clinical efficacy of XAV-19 was investigated in patients with a WHO score of 2 to 4 in the WHO 7-point ordinal scale. The activity of XAV-19 against Omicron and its subvariants was assessed in vitro. Methods: A phase II/III, multicentric randomized double-blind placebo-controlled, clinical trial was conducted to evaluate the safety and clinical efficacy of XAV-19 in inpatients with COVID-19 requiring or not oxygen therapy and outpatients not requiring oxygen (EUROXAV trial, NCT04928430). Most patients were not vaccinated. The primary endpoint was the proportion of patients with an aggravation of COVID-19 within 8 days after treatment. Binding and neutralization of Omicron or its subvariants by XAV-19 was investigated by ELISA or with a whole virus neutralization assay. Results: Patients received either 150mg of XAV-19 (N=139) or placebo (N=140). Low enrolment forced the premature trial termination. XAV-19 was well tolerated. No difference in the primary endpoint, nor in the proportion with an improvement at day 8 (secondary endpoint) was observed between the 2 groups. For patients not requiring oxygen therapy, XAV-19 reduced the time to improvement significantly (7 days vs 14 days p=0.0159). Neutralizing activity against Omicron and BA.2, BA2.12.1, BA.4/5 and BQ1.1 subvariants was shown in vitro. Conclusions: XAV-19 did not reduce the aggravation in COVID-19 patients. While it did not bring any benefit to patients requiring oxygen, it reduced the time to improvement for patients not requiring oxygen (WHO score 2 or 3). These preliminary clinical data might indicate a therapeutic potential for patients with mild to moderate COVID-19 requiring supplementation with anti-SARS-CoV-2 neutralizing antibodies.
Keywords	covid19
Language	English
Publishing date	2023-10-19
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2023.10.09.23296726
Database	COVID19

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Article ; Online: Corrigendum: XAV-19, a swine glyco-humanized polyclonal antibody against SARS-CoV-2 spike receptor-binding domain, targets multiple epitopes and broadly neutralizes variants.

Vanhove, Bernard / Marot, Stéphane / So, Ray T / Gaborit, Benjamin / Evanno, Gwénaëlle / Malet, Isabelle / Lafrogne, Guillaume / Mevel, Edwige / Ciron, Carine / Royer, Pierre-Joseph / Lheriteau, Elsa / Raffi, François / Bruzzone, Roberto / Mok, Chris Ka Pun / Duvaux, Odile / Marcelin, Anne-Geneviève / Calvez, Vincent

Frontiers in immunology

2023 Volume 14, Page(s) 1208705

Abstract: This corrects the article DOI: 10.3389/fimmu.2021.761250.]. ...

Abstract	[This corrects the article DOI: 10.3389/fimmu.2021.761250.].
Language	English
Publishing date	2023-04-28
Publishing country	Switzerland
Document type	Published Erratum
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1208705
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Article ; Online: LIS1, a glyco-humanized swine polyclonal anti-lymphocyte globulin, as a novel induction treatment in solid organ transplantation.

Rousse, Juliette / Royer, Pierre-Joseph / Evanno, Gwénaëlle / Lheriteau, Elsa / Ciron, Carine / Salama, Apolline / Shneiker, Françoise / Duchi, Roberto / Perota, Andrea / Galli, Cesare / Cozzi, Emmanuele / Blancho, Gilles / Duvaux, Odile / Brouard, Sophie / Soulillou, Jean-Paul / Bach, Jean-Marie / Vanhove, Bernard

Frontiers in immunology

2023 Volume 14, Page(s) 1137629

Abstract: Anti-thymocyte or anti-lymphocyte globulins (ATGs/ALGs) are immunosuppressive drugs used in induction therapies to prevent acute rejection in solid organ transplantation. Because animal-derived, ATGs/ALGs contain highly immunogenic carbohydrate ... ...

Abstract	Anti-thymocyte or anti-lymphocyte globulins (ATGs/ALGs) are immunosuppressive drugs used in induction therapies to prevent acute rejection in solid organ transplantation. Because animal-derived, ATGs/ALGs contain highly immunogenic carbohydrate xenoantigens eliciting antibodies that are associated with subclinical inflammatory events, possibly impacting long-term graft survival. Their strong and long-lasting lymphodepleting activity also increases the risk for infections. We investigated here the
MeSH term(s)	Rabbits ; Animals ; Swine ; Organ Transplantation ; Lymphocytes ; Transplantation, Homologous ; Globulins ; B-Lymphocytes
Chemical Substances	Globulins
Language	English
Publishing date	2023-02-16
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.2023.1137629
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Article ; Online: XAV-19 a Glyco-Humanized polyclonal antibody targeting SARS-CoV-2 accelerates the recovery of mild to moderate COVID-19 patients and keeps its neutralizing activity against Omicron and its subvariants.

Poulakou, Garyfallia / Royer, Pierre-Joseph / Evgeniev, Nikolai / Evanno, Gwenaëlle / Shneiker, Françoise / Marcelin, Anne-Geneviève / Vanhove, Bernard / Duvaux, Odile / Marot, Stéphane / Calvez, Vincent

medRxiv

Abstract	Background: XAV-19 is a glyco-humanized swine polyclonal antibody targeting SARS-CoV-2. The safety and clinical efficacy of XAV-19 was investigated in patients with a WHO score of 2 to 4 in the WHO 7-point ordinal scale. The activity of XAV-19 against Omicron and its subvariants was assessed in vitro. Methods: A phase II/III, multicentric randomized double-blind placebo-controlled, clinical trial was conducted to evaluate the safety and clinical efficacy of XAV-19 in inpatients with COVID-19 requiring or not oxygen therapy and outpatients not requiring oxygen (EUROXAV trial, NCT04928430). Most patients were not vaccinated. The primary endpoint was the proportion of patients with an aggravation of COVID-19 within 8 days after treatment. Binding and neutralization of Omicron or its subvariants by XAV-19 was investigated by ELISA or with a whole virus neutralization assay. Results: Patients received either 150mg of XAV-19 (N=139) or placebo (N=140). Low enrolment forced the premature trial termination. XAV-19 was well tolerated. No difference in the primary endpoint, nor in the proportion with an improvement at day 8 (secondary endpoint) was observed between the 2 groups. For patients not requiring oxygen therapy, XAV-19 reduced the time to improvement significantly (7 days vs 14 days p=0.0159). Neutralizing activity against Omicron and BA.2, BA2.12.1, BA.4/5 and BQ1.1 subvariants was shown in vitro. Conclusions: XAV-19 did not reduce the aggravation in COVID-19 patients. While it did not bring any benefit to patients requiring oxygen, it reduced the time to improvement for patients not requiring oxygen (WHO score 2 or 3). These preliminary clinical data might indicate a therapeutic potential for patients with mild to moderate COVID-19 requiring supplementation with anti-SARS-CoV-2 neutralizing antibodies.
Keywords	covid19
Language	English
Publishing date	2023-10-19
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2023.10.09.23296726
Database	COVID19

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Article ; Online: Anti-SARS-CoV-2 swine glyco-humanized polyclonal antibody XAV-19 retains neutralizing activity against SARS-CoV-2 B.1.1.529 (Omicron)

Vanhove, Bernard / Marot, Stephane Sylvain / Evanno, Gwenaelle / Mallet, Isabelle / Rouvray, Gaetane / Shneiker, Francoise / Mevel, Edwige / Ciron, Carine / Rousse, Juliette / Royer, Pierre-Joseph / Lheriteau, Elsa / Raffi, Francois / Duvaux, Odile / Marcelin, Anne-Genevieve / Calvez, Vincent

bioRxiv

Abstract: B.1.1.529 is the SARS-CoV-2 variant designated Omicron by the WHO in November 2021. It is a highly divergent variant with a high number of mutations, including 26-32 mutations in the spike protein among which 15 in the Receptor Binding Domain (RBD) ... ...

Abstract	B.1.1.529 is the SARS-CoV-2 variant designated Omicron by the WHO in November 2021. It is a highly divergent variant with a high number of mutations, including 26-32 mutations in the spike protein among which 15 in the Receptor Binding Domain (RBD) including at the human angiotensin converting enzyme 2 (ACE-2) receptor interacting interface. Because of a decreased affinity for the ACE-2 receptor and a geometric reorganization of the S1-S2 cleavage site, the Omicron variant is predicted to not have a significant infectivity advantage over the delta variant and to be less pathogenic than Delta. However, in Omicron, neutralizing epitopes are greatly affected, suggesting that current vaccines and neutralizing monoclonal antibodies might confer reduced protection against this variant. In contrast, we and others previously demonstrated that polyclonal antibodies against SARS-CoV-2 RBD obtained from hyperimmunized animal hosts do maintain their neutralizing properties against Alpha to Delta. Here, we confirmed these findings by showing that XAV-19, a swine glyco-humanized polyclonal antibody retains full neutralizing activity against Omicron.
Keywords	covid19
Language	English
Publishing date	2022-01-26
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2022.01.26.477856
Database	COVID19

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Article: Plasma Acute Phase Proteins as Predictors of Chronic Lung Allograft Dysfunction in Lung Transplant Recipients.

Janciauskiene, Sabina / Royer, Pierre-Joseph / Fuge, Jan / Wrenger, Sabine / Chorostowska-Wynimko, Joanna / Falk, Christine / Welte, Tobias / Reynaud-Gaubert, Martine / Roux, Antoine / Tissot, Adrien / Magnan, Antoine

Journal of inflammation research

2020 Volume 13, Page(s) 1021–1028

Abstract: Cumulating reports suggest that acute phase proteins (APPs) have diagnostic and prognostic value in different clinical conditions. Among others, APPs are proposed to serve as markers that help to control the outcome of transplant recipients. Here, we ... ...

Abstract	Cumulating reports suggest that acute phase proteins (APPs) have diagnostic and prognostic value in different clinical conditions. Among others, APPs are proposed to serve as markers that help to control the outcome of transplant recipients. Here, we questioned whether plasma concentrations of APPs mirror the development of chronic lung allograft dysfunction (CLAD). We performed blinded analysis of serial plasma samples retrospectively collected from 35 lung transplanted patients, of whom 25 developed CLAD and 10 remained stable during the follow-up period of 3 to 4.5 years. Albumin (ALB), alpha1-antitrypsin (AAT), high sensitivity C-reactive protein (CRPH), antithrombin-3 (AT3), ceruloplasmin (CER), and alpha2-macroglobulin (A2MG) were measured by the nephelometric method. We found that within the first six months post-transplantation, levels of A2MG, CER and AAT were higher in stable patients relative to those who later developed CLAD. Moreover, in stable patient's plasma CRPH levels decreased during the follow-up period whereas opposite, in those developing CLAD, the CRPH gradually increased. The ALB levels became significantly lower at the end of the follow-up period in CLAD relative to a stable group. A logistic regression model based on A2MG, CER and AT3 at cut-offs levels of ≥175.5 mg/dL, ≥37.8 mg/dL and ≥27.35 mg/dL enabled to discriminate between stable and CLAD patients with a sensitivity of 87.5%, 100% and 62.5%, and specificity of 65.9%, 72.7% and 79.5%, respectively. We identified A2MG (below 175.5 mg/dL) as an independent predictor of CLAD (hazard ratio 11.5, 95% CI (1.5-91.3), p<0.021). Our findings suggest that profiles of certain APPs may help to predict the development of lung dysfunction at the very early stages after transplantation.
Language	English
Publishing date	2020-11-30
Publishing country	New Zealand
Document type	Case Reports ; Clinical Trial
ZDB-ID	2494878-0
ISSN	1178-7031
ISSN	1178-7031
DOI	10.2147/JIR.S272662
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Article ; Online: XAV-19, a Swine Glyco-Humanized Polyclonal Antibody Against SARS-CoV-2 Spike Receptor-Binding Domain, Targets Multiple Epitopes and Broadly Neutralizes Variants.

Frontiers in immunology

2021 Volume 12, Page(s) 761250

Abstract: Amino acid substitutions and deletions in the Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants can reduce the effectiveness of monoclonal antibodies (mAbs). In contrast, heterologous polyclonal antibodies raised ... ...

Abstract	Amino acid substitutions and deletions in the Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants can reduce the effectiveness of monoclonal antibodies (mAbs). In contrast, heterologous polyclonal antibodies raised against S protein, through the recognition of multiple target epitopes, have the potential to maintain neutralization capacities. XAV-19 is a swine glyco-humanized polyclonal neutralizing antibody raised against the receptor binding domain (RBD) of the Wuhan-Hu-1 Spike protein of SARS-CoV-2. XAV-19 target epitopes were found distributed all over the RBD and particularly cover the receptor binding motives (RBMs), in direct contact sites with the angiotensin converting enzyme-2 (ACE-2). Therefore, in Spike/ACE-2 interaction assays, XAV-19 showed potent neutralization capacities of the original Wuhan Spike and of the United Kingdom (Alpha/B.1.1.7) and South African (Beta/B.1.351) variants. These results were confirmed by cytopathogenic assays using Vero E6 and live virus variants including the Brazil (Gamma/P.1) and the Indian (Delta/B.1.617.2) variants. In a selective pressure study on Vero E6 cells conducted over 1 month, no mutation was associated with the addition of increasing doses of XAV-19. The potential to reduce viral load in lungs was confirmed in a human ACE-2 transduced mouse model. XAV-19 is currently evaluated in patients hospitalized for COVID-19-induced moderate pneumonia in phase 2a-2b (NCT04453384) where safety was already demonstrated and in an ongoing 2/3 trial (NCT04928430) to evaluate the efficacy and safety of XAV-19 in patients with moderate-to-severe COVID-19. Owing to its polyclonal nature and its glyco-humanization, XAV-19 may provide a novel safe and effective therapeutic tool to mitigate the severity of coronavirus disease 2019 (COVID-19) including the different variants of concern identified so far.
MeSH term(s)	Animals ; Antibodies, Heterophile/immunology ; Antibodies, Heterophile/therapeutic use ; Antibodies, Viral/immunology ; Antibodies, Viral/therapeutic use ; Antigenic Variation ; Broadly Neutralizing Antibodies/immunology ; Broadly Neutralizing Antibodies/therapeutic use ; COVID-19/therapy ; COVID-19/virology ; Disease Models, Animal ; Epitopes ; Humans ; Immunization, Passive ; Lung/drug effects ; Lung/virology ; Mice ; Protein Interaction Domains and Motifs ; SARS-CoV-2/immunology ; Spike Glycoprotein, Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/immunology ; Swine ; Viral Load/drug effects ; COVID-19 Serotherapy
Chemical Substances	Antibodies, Heterophile ; Antibodies, Viral ; Broadly Neutralizing Antibodies ; Epitopes ; Spike Glycoprotein, Coronavirus ; XAV-19 ; spike protein, SARS-CoV-2
Language	English
Publishing date	2021-11-15
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.761250
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Article: Systems prediction of chronic lung allograft dysfunction: Results and perspectives from the Cohort of Lung Transplantation and Systems prediction of Chronic Lung Allograft Dysfunction cohorts.

Pison, Christophe / Tissot, Adrien / Bernasconi, Eric / Royer, Pierre-Joseph / Roux, Antoine / Koutsokera, Angela / Coiffard, Benjamin / Renaud-Picard, Benjamin / Le Pavec, Jérôme / Mordant, Pierre / Demant, Xavier / Villeneuve, Thomas / Mornex, Jean-Francois / Nemska, Simona / Frossard, Nelly / Brugière, Olivier / Siroux, Valérie / Marsland, Benjamin J / Foureau, Aurore /

Botturi, Karine / Durand, Eugenie / Pellet, Johann / Danger, Richard / Auffray, Charles / Brouard, Sophie / Nicod, Laurent / Magnan, Antoine

Frontiers in medicine

2023 Volume 10, Page(s) 1126697

Abstract: Background: Chronic lung allograft dysfunction (CLAD) is the leading cause of poor long-term survival after lung transplantation (LT). Systems prediction of Chronic Lung Allograft Dysfunction (SysCLAD) aimed to predict CLAD.: Methods: To predict CLAD, ...

Abstract	Background: Chronic lung allograft dysfunction (CLAD) is the leading cause of poor long-term survival after lung transplantation (LT). Systems prediction of Chronic Lung Allograft Dysfunction (SysCLAD) aimed to predict CLAD. Methods: To predict CLAD, we investigated the clinicome of patients with LT; the exposome through assessment of airway microbiota in bronchoalveolar lavage cells and air pollution studies; the immunome with works on activation of dendritic cells, the role of T cells to promote the secretion of matrix metalloproteinase-9, and subpopulations of T and B cells; genome polymorphisms; blood transcriptome; plasma proteome studies and assessment of MSK1 expression. Results: Clinicome: the best multivariate logistic regression analysis model for early-onset CLAD in 422 LT eligible patients generated a ROC curve with an area under the curve of 0.77. Exposome: chronic exposure to air pollutants appears deleterious on lung function levels in LT recipients (LTRs), might be modified by macrolides, and increases mortality. Our findings established a link between the lung microbial ecosystem, human lung function, and clinical stability post-transplant. Immunome: a decreased expression of CLEC1A in human lung transplants is predictive of the development of chronic rejection and associated with a higher level of interleukin 17A; Immune cells support airway remodeling through the production of plasma MMP-9 levels, a potential predictive biomarker of CLAD. Blood CD9-expressing B cells appear to favor the maintenance of long-term stable graft function and are a potential new predictive biomarker of BOS-free survival. An early increase of blood CD4 + CD57 + ILT2+ T cells after LT may be associated with CLAD onset. Genome: Donor Club cell secretory protein G38A polymorphism is associated with a decreased risk of severe primary graft dysfunction after LT. Transcriptome: blood POU class 2 associating factor 1, T-cell leukemia/lymphoma domain, and B cell lymphocytes, were validated as predictive biomarkers of CLAD phenotypes more than 6 months before diagnosis. Proteome: blood A2MG is an independent predictor of CLAD, and MSK1 kinase overexpression is either a marker or a potential therapeutic target in CLAD. Conclusion: Systems prediction of Chronic Lung Allograft Dysfunction generated multiple fingerprints that enabled the development of predictors of CLAD. These results open the way to the integration of these fingerprints into a predictive handprint.
Language	English
Publishing date	2023-03-09
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2023.1126697
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