Article
Medicine, Research & Experimental
Aaditya Khatri, Jamie L. . Todd, Fran L. . Kelly, Andrew Nagler, Zhicheng Ji, Vaibhav Jain, Simon G. Gregory, Kent J. Weinhold, Scott M. Palmer
Summary: Chronic lung allograft dysfunction (CLAD), characterized by decline in pulmonary function and bronchiolitis obliterans, lacks approved therapies. Single-cell RNA-Seq and spatial transcriptomic analysis identified the important role of JAK-STAT signaling in airway epithelial cells in CLAD. Activation of JAK-STAT signaling leads to upregulation of MHC-I in airway basal cells, resulting in cytotoxic T cell-mediated basal cell death. This study provides mechanistic insight and potential therapeutic strategy for CLAD.
Article
Hematology
Yifan Pang, Ananth Charya, Michael B. Keller, Arlene Sirajuddin, Yi-Ping Fu, Noa G. Holtzman, Steven Z. Pavletic, Sean Agbor-Enoh
Summary: This study adapted the 2019 International Society for Heart and Lung Transplantation criteria to define novel phenotypes of pulmonary chronic graft-versus-host disease (PcGVHD) and compared its performance with the NIH criteria in identifying high-risk PcGVHD patients. The adapted criteria were found to be effective in identifying high-risk PcGVHD patients that were missed by the NIH criteria.
Article
Medicine, General & Internal
Jesper Romhild Davidsen, Christian B. Laursen, Mikkel Hojlund, Thomas Kromann Lund, Klaus Nielsen Jeschke, Martin Iversen, Anna Kalhauge, Elisabeth Bendstrup, Jorn Carlsen, Michael Perch, Daniel Pilsgaard Henriksen, Hans Henrik Lawaetz Schultz
Summary: This study found that pleural thickening identified by lung ultrasound may serve as a potential surrogate marker to distinguish restrictive allograft syndrome (RAS) from bronchiolitis obliterans syndrome (BOS) in chronic lung allograft dysfunction (CLAD) patients after lung transplant. This discovery provides a new method for clinical diagnosis of CLAD patients post lung transplant.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Jens Gottlieb, Geert M. Verleden, Michael Perchl, Christina Valtin, Alexander Vallee, Olivier Brugiere, Carlos Bravo
Summary: The poor outcomes of the two specific CLAD phenotypes suggest the urgent need for future therapeutic randomized trials. The high number of missing values in a potential trial is most frequently attributed to death. Survival may be used as an endpoint in clinical trials in these distinct phenotypes, and imputation techniques are relevant if graft function is used as a surrogate of disease progression in future trials.
Article
Respiratory System
Micheal C. McInnis, Jin Ma, Gauri Rani Karur, Christian Houbois, Liran Levy, Jan Havlin, Eyal Fuchs, Jussi Tikkanen, Chung-Wai Chow, Ella Huszti, Tereza Martinu
Summary: In this study, a machine learning computed tomography (CT) lung texture analysis tool was used for phenotyping and prognostication of chronic lung allograft dysfunction (CLAD) in lung transplant recipients. The results showed that machine learning could effectively distinguish different CLAD phenotypes, and the associated parameters were able to predict the risk of graft failure.
EUROPEAN RESPIRATORY JOURNAL
(2022)
Article
Surgery
Naofumi Miyahara, Alberto Benazzo, Felicitas Oberndorfer, Akinori Iwasaki, Viktoria Laszlo, Balasz Dome, Mir Ali Hoda, Peter Jaksch, Walter Klepetko, Konrad Hoetzenecker
Summary: miR-21 expression was higher in restrictive allograft syndrome (RAS) than in bronchiolitis obliterans syndrome (BOS) specimens, with a significant increase in serum concentration over time in RAS patients. Vimentin, NICD, and p-SMAD 2/3 were positive in a higher proportion of BOS patients compared to RAS cases.
TRANSPLANT INTERNATIONAL
(2022)
Review
Transplantation
Geert M. Verleden, Laurent Godinas, Robin Vos, Stijn E. Verleden
Summary: New consensus documents on chronic lung allograft dysfunction (CLAD) were published in 2019, defining four different phenotypes. Recent studies have shown that precise phenotyping based on pulmonary function alone can be challenging. Regular chest computed tomography scanning appears to be very helpful in determining the prognosis of CLAD patients. Changes in pulmonary function may not always accurately identify the exact phenotype of CLAD, highlighting the important role of chest imaging in diagnosis and follow-up.
CURRENT OPINION IN ORGAN TRANSPLANTATION
(2022)
Article
Immunology
Tatsuaki Watanabe, Christina Lam, Jillian Oliver, Hisashi Oishi, Grace Teskey, Samuel Beber, Kristen Boonstra, Juan Mauricio Umana, Hifza Buhari, Betty Joe, Zehong Guan, Miho Horie, Shaf Keshavjee, Tereza Martinu, Stephen C. Juvet
Summary: Chronic lung allograft dysfunction (CLAD) is a major obstacle in the survival of lung transplant patients. This study investigated the role of a specific type of dendritic cells (cDC1) in CLAD using a mouse lung transplant model. The results showed that cDC1s accumulated in the transplanted lungs and their activation was enhanced by airway inflammation. Furthermore, the absence of BATF3, a transcription factor essential for cDC1 development, had differential effects on acute rejection and T-cell expansion depending on the presence of airway inflammation.
MUCOSAL IMMUNOLOGY
(2023)
Article
Critical Care Medicine
Jarrod E. Dalton, Carli J. Lehr, Paul R. Gunsalus, Lyla Mourany, Maryam Valapour
Summary: This study examined the performance of models predicting waitlist and posttransplant survival in lung transplant allocation. The results showed that different models had similar performance in predicting waitlist and posttransplant survival, and using alternative modeling strategies and contemporary cohorts did not improve the models' performance in determining access to lung transplant.
Article
Surgery
Kei Matsubara, Shinji Otani, Haruchika Yamamoto, Kohei Hashimoto, Shin Tanaka, Kazuhiko Shien, Ken Suzawa, Kentaroh Miyoshi, Hiromasa Yamamoto, Mikio Okazaki, Seiichiro Sugimoto, Shinichi Toyooka
Summary: This study evaluated the CLAD classification of ISHLT for LDLLT. The results showed that CLAD after bilateral LDLLT does not have a major impact on recipient survival, especially in patients with BOS. The restriction on PFT may predict a particularly poor prognosis in patients with CLAD after bilateral LDLLT.
Article
Pharmacology & Pharmacy
Filippo Patrucco, Elias Allara, Massimo Boffini, Mauro Rinaldi, Cristina Costa, Carlo Albera, Paolo Solidoro
Summary: Chronic lung allograft dysfunction (CLAD) affects the survival of lung transplant patients and includes bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). This study evaluated the 12-month follow-up of renal and lung function in lung transplant patients treated with everolimus, showing improvements in renal function and sustained improvements in lung function for CLAD related to BOS subgroup results, while RAS confirmed a worsening trend over a year.
THERAPEUTIC ADVANCES IN CHRONIC DISEASE
(2021)
Article
Immunology
Vaidehi Kaza, Chengsong Zhu, Lance S. Terada, Li Wang, Fernando Torres, Srinivas Bollineni, Manish Mohanka, Amit Banga, John Joerns, T. Mohanakumar, Quan-Zhen Li
Summary: This study found that pre-existing elevated IgG autoantibodies are significantly correlated with progressive BOS and worse survival in lung transplant recipients. The findings suggest important implications for predicting long term survival after lung transplantation.
Review
Medicine, General & Internal
Trieu-Nghi Hoang-Thi, Guillaume Chassagnon, Thong Hua-Huy, Veronique Boussaud, Anh-Tuan Dinh-Xuan, Marie-Pierre Revel
Summary: Quantitative imaging methods play a key role in early identification and prognostic estimation of CLAD, with the need for novel approaches to predict, understand, and identify CLAD in its early stages. However, there are limitations to be addressed in quantitative imaging for evaluating CLAD.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Medicine, General & Internal
Christophe Pison, Adrien Tissot, Eric Bernasconi, Pierre-Joseph Royer, Antoine Roux, Angela Koutsokera, Benjamin Coiffard, Benjamin Renaud-Picard, Jerome Le Pavec, Pierre Mordant, Xavier Demant, Thomas Villeneuve, Jean-Francois Mornex, Simona Nemska, Nelly Frossard, Olivier Brugiere, Valerie J. Siroux, Benjamin Marsland, Aurore Foureau, Karine Botturi, Eugenie Durand, Johann Pellet, Richard Danger, Charles Auffray, Sophie Brouard, Laurent Nicod, Antoine Magnan
Summary: SysCLAD is a research aiming to predict chronic lung allograft dysfunction (CLAD), which involves investigating various factors including clinical data, assessment of airway microbiota, air pollution studies, activation of immune cells, secretion of matrix metalloproteinase-9 by T cells, subpopulations of T and B cells, genome polymorphisms, blood transcriptome, plasma proteome studies, and MSK1 expression to develop predictors of CLAD.
FRONTIERS IN MEDICINE
(2023)
Article
Immunology
Jaideep Vazirani, David Routledge, Greg Snell, Doug Watson, Miranda Paraskeva, Glen P. Westall, Simon J. Harrison
Summary: In a retrospective audit of 12 LTx recipients with CLAD receiving rescue ECP, 67% responded positively to therapy. Factors such as sex, pre-ECP neutrophil count, and prior exposure to anti-thymocyte globulin may impact the response to ECP in CLAD patients, highlighting the need for further clinical trials to confirm efficacy and guide treatment decisions.
TRANSPLANTATION PROCEEDINGS
(2021)
Article
Immunology
Kellie J. Goodlet, Sandhya Bansal, Ashwini Arjuna, Michael D. Nailor, Bhuvin Buddhdev, Hesham Abdelrazek, Hesham Mohamed, Ashraf Omar, Rajat Walia, Thalachallour Mohanakumar, Sofya Tokman
Summary: Exosomes isolated from plasma of lung transplant recipients contain lung self-antigens and HLA molecules, which can be used to monitor allograft injury. Analysis of exosomes allows for detection of transplant injury mediated by rejection and infection, including viral proteins.
TRANSPLANT INFECTIOUS DISEASE
(2021)
Article
Immunology
Yoshihiro Itabashi, Ranjithkumar Ravichandran, Sandhya Bansal, Ankit Bharat, Ramsey Hachem, Ross Bremner, Michael Smith, T. Mohanakumar
Summary: The study found that lung transplant recipients with BOS had lower CCSP levels up to 9 months before BOS diagnosis, and those with SAgs antibodies 1 year post-transplant also developed DSA and had lower CCSP. Exosomes from BOS contained increased SAgs, NK cells markers, and cytotoxic molecules.
Article
Biophysics
Jessica Bodea, Kristen Beebe, Courtney Campbell, Dana Salzberg, Holly Miller, Roberta Adams, Lucia Mirea, Paul Castillo, Biljana Horn, Sandhya Bansal, Thalachallour Mohanakumar, Alexander Ngwube
Summary: The study showed that high-dose oral vitamin D therapy (Stoss therapy) is a safe and effective treatment option for vitamin D deficiency in children undergoing HSCT, allowing for quicker attainment of adequate vitamin D levels compared to standard of care.
BONE MARROW TRANSPLANTATION
(2021)
Article
Cardiac & Cardiovascular Systems
Hadi Javan, Ling Li, Christin L. Schaaf, Young Sook Lee, Mohamed E. Salama, Charles A. Dinarello, Craig H. Selzman
Summary: IL-1 blockade prevents the progression of heart failure associated with acute pressure overload by reducing fibrosis, cellular infiltration, and cytokine production. These findings provide mechanistic insights and may drive future investigations in patients with pressure-overload-based cardiomyopathies.
ANNALS OF THORACIC SURGERY
(2022)
Article
Cardiac & Cardiovascular Systems
Ranjithkumar Ravichandran, Yoshihiro Itabashi, Wei Liu, Sandhya Bansal, Mohammad Rahman, Christin Poulson, Timothy Fleming, Ross M. Bremner, Michael Smith, Thalachallour Mohanakumar
Summary: The study explored the mechanisms by which a decline in CCSP contributes to chronic lung allograft rejection in mouse models. It was found that induction of exosomes led to immune responses to donor MHC and lung self-antigens, resulting in CCSP decline, NK cell infiltration, and release of exosomes from NK cells. The results suggest a novel role for exosomes derived from NK cells in the pathogenesis of chronic lung allograft rejection.
JOURNAL OF HEART AND LUNG TRANSPLANTATION
(2021)
Article
Surgery
Mohammad Rahman, Ranjithkumar Ravichandran, Sandhya Bansal, Kristina Sanborn, Sara Bowen, Jennifer Eschbacher, Angara Sureshbabu, Timothy Fleming, Ankit Bharat, Rajat Walia, Ramsey Hachem, Ross M. Bremner, Michael A. Smith, Thalachallour Mohanakumar
Summary: The study investigates the role of LKB1 in the development of CLAD following lung transplantation, revealing that downregulation of LKB1 is associated with EMT occurrence. Exosomes from lungs undergoing chronic rejection are linked to inactivation of LKB1, leading to EMT and the pathogenesis of CLAD.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Article
Cardiac & Cardiovascular Systems
Deepika Razia, Sumeet K. Mittal, Sandhya Bansal, Ranjithkumar Ravichandran, Luca Giulini, Michael A. Smith, Rajat Walia, Thalachallour Mohanakumar, Ross M. Bremner
SEMINARS IN THORACIC AND CARDIOVASCULAR SURGERY
(2022)
Article
Transplantation
Deepika Razia, Sumeet K. Mittal, Sandhya Bansal, Ranjithkumar Ravichandran, Michael A. Smith, Rajat Walia, Ross M. Bremner, Thalachallour Mohanakumar, Sofya Tokman
Summary: This study found that pre-lung transplant gastroesophageal reflux (GER) or circulating antibodies against lung self-antigens (SAbs) may increase the risk of chronic lung allograft dysfunction (CLAD) in recipients. The association suggests that GER may cause an immune response to lung-associated self-antigens, leading to ongoing lung injury.
TRANSPLANTATION DIRECT
(2022)
Article
Surgery
Ranjithkumar Ravichandran, Yoshihiro Itabashi, Timothy Fleming, Sandhya Bansal, Sara Bowen, Christin Poulson, Ankit Bharat, Ross Bremner, Michael Smith, Thalachallour Mohanakumar
Summary: Low-dose IL-2 treatment delays chronic cardiac allograft rejection and induces the generation of regulatory cells and circulating exosomes with immunoregulatory molecules.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Review
Microbiology
Pramod Yadav, Raja Singh, Souvik Sur, Sandhya Bansal, Uma Chaudhry, Vibha Tandon
Summary: Moonlighting proteins (MLPs) are ubiquitous and provide a unique advantage to bacteria performing multiple functions. Targeting MLPs is considered as a hopeful approach to combat drug resistance in bacteria.
CRITICAL REVIEWS IN MICROBIOLOGY
(2023)
Article
Immunology
Yoshihiro Itabashi, Ranjithkumar Ravichandran, Sandhya Bansal, Chiahsuan Chin, Christin Poulson, Angara Sureshbabu, Sumi Sukumaran Nair, Sudhir Perincheri, T. Mohanakumar
Summary: This study investigates the role of exosomes in chronic immune injury following renal transplantation. The results suggest that exosomes may induce immune and autoimmune responses to allo- and self-antigens, leading to the development of chronic immune injury.
TRANSPLANT IMMUNOLOGY
(2022)
Meeting Abstract
Cardiac & Cardiovascular Systems
R. Ravichandran, Y. Itabashi, W. Liu, C. Poulson, T. Fleming, T. Mohanakumar
JOURNAL OF HEART AND LUNG TRANSPLANTATION
(2021)