LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 6 of total 6

Search options

  1. Article: Cell-free Chromatin Immunoprecipitation to detect molecular pathways in Physiological and Disease States.

    Jang, Moon K / Markowitz, Tovah E / Andargie, Temesgen E / Apalara, Zainab / Kuhn, Skyler / Agbor-Enoh, Sean

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Patient monitoring is a cornerstone in clinical practice to define disease phenotypes and guide clinical management. Unfortunately, this is often reliant on invasive and/or less sensitive methods that do not provide deep phenotype assessments of disease ... ...

    Abstract Patient monitoring is a cornerstone in clinical practice to define disease phenotypes and guide clinical management. Unfortunately, this is often reliant on invasive and/or less sensitive methods that do not provide deep phenotype assessments of disease state to guide treatment. This paper examined plasma cell-free DNA chromatin immunoprecipitation sequencing (cfChIP-seq) to define molecular gene sets in physiological and heart transplant patients taking immunosuppression medications. We show cfChIP-seq reliably detect gene signals that correlate with gene expression. In healthy controls and in heart transplant patients, cfChIP-seq reliably detected housekeeping genes. cfChIP-seq identified differential gene signals of the relevant immune and non-immune molecular pathways that were predominantly downregulated in immunosuppressed heart transplant patients compared to healthy controls. cfChIP-seq also identified tissue sources of cfDNA, detecting greater cell-free DNA from cardiac, hematopoietic, and other non-hematopoietic tissues such as the pulmonary, digestive, and neurological tissues in transplant patients than healthy controls. cfChIP-seq gene signals were reproducible between patient populations and blood collection methods. cfChIP-seq may therefore be a reliable approach to provide dynamic assessments of molecular pathways and tissue injury associated to disease.
    Language English
    Publishing date 2023-01-25
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.01.24.525414
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  2. Article ; Online: Cell-free DNA reveals distinct pathology of multisystem inflammatory syndrome in children.

    Andargie, Temesgen E / Roznik, Katerina / Redekar, Neelam / Hill, Tom / Zhou, Weiqiang / Apalara, Zainab / Kong, Hyesik / Gordon, Oren / Meda, Rohan / Park, Woojin / Johnston, Trevor S / Wang, Yi / Brady, Sheila / Ji, Hongkai / Yanovski, Jack A / Jang, Moon K / Lee, Clarence M / Karaba, Andrew H / Cox, Andrea L /
    Agbor-Enoh, Sean

    The Journal of clinical investigation

    2024  Volume 134, Issue 1

    Language English
    Publishing date 2024-01-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI178008
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  3. Article ; Online: The SIRPα-CD47 immune checkpoint in NK cells.

    Deuse, Tobias / Hu, Xiaomeng / Agbor-Enoh, Sean / Jang, Moon K / Alawi, Malik / Saygi, Ceren / Gravina, Alessia / Tediashvili, Grigol / Nguyen, Vinh Q / Liu, Yuan / Valantine, Hannah / Lanier, Lewis L / Schrepfer, Sonja

    The Journal of experimental medicine

    2021  Volume 218, Issue 3

    Abstract: Here we report on the existence and functionality of the immune checkpoint signal regulatory protein α (SIRPα) in NK cells and describe how it can be modulated for cell therapy. NK cell SIRPα is up-regulated upon IL-2 stimulation, interacts with target ... ...

    Abstract Here we report on the existence and functionality of the immune checkpoint signal regulatory protein α (SIRPα) in NK cells and describe how it can be modulated for cell therapy. NK cell SIRPα is up-regulated upon IL-2 stimulation, interacts with target cell CD47 in a threshold-dependent manner, and counters other stimulatory signals, including IL-2, CD16, or NKG2D. Elevated expression of CD47 protected K562 tumor cells and mouse and human MHC class I-deficient target cells against SIRPα+ primary NK cells, but not against SIRPα- NKL or NK92 cells. SIRPα deficiency or antibody blockade increased the killing capacity of NK cells. Overexpression of rhesus monkey CD47 in human MHC-deficient cells prevented cytotoxicity by rhesus NK cells in a xenogeneic setting. The SIRPα-CD47 axis was found to be highly species specific. Together, the results demonstrate that disruption of the SIRPα-CD47 immune checkpoint may augment NK cell antitumor responses and that elevated expression of CD47 may prevent NK cell-mediated killing of allogeneic and xenogeneic tissues.
    MeSH term(s) Animals ; CD47 Antigen/metabolism ; Cells, Cultured ; Cytokines/pharmacology ; Cytotoxicity, Immunologic/drug effects ; Endothelial Cells/drug effects ; Endothelial Cells/metabolism ; Histocompatibility Antigens Class I/metabolism ; Humans ; Immune Checkpoint Inhibitors ; Killer Cells, Natural/drug effects ; Killer Cells, Natural/metabolism ; Macaca mulatta ; Macrophages/drug effects ; Macrophages/metabolism ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Protein Binding/drug effects ; Receptors, Immunologic/metabolism ; Species Specificity ; Mice
    Chemical Substances CD47 Antigen ; Cytokines ; Histocompatibility Antigens Class I ; Immune Checkpoint Inhibitors ; Ptpns1 protein, mouse ; Receptors, Immunologic
    Language English
    Publishing date 2021-01-08
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 218343-2
    ISSN 1540-9538 ; 0022-1007
    ISSN (online) 1540-9538
    ISSN 0022-1007
    DOI 10.1084/jem.20200839
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  4. Article ; Online: Cell-free DNA reveals distinct pathology of multisystem inflammatory syndrome in children.

    Andargie, Temesgen E / Roznik, Katerina / Redekar, Neelam / Hill, Tom / Zhou, Weiqiang / Apalara, Zainab / Kong, Hyesik / Gordon, Oren / Meda, Rohan / Park, Woojin / Johnston, Trevor S / Wang, Yi / Brady, Sheila / Ji, Hongkai / Yanovski, Jack A / Jang, Moon K / Lee, Clarence M / Karaba, Andrew H / Cox, Andrea L /
    Agbor-Enoh, Sean

    The Journal of clinical investigation

    2023  Volume 133, Issue 21

    Abstract: Multisystem inflammatory syndrome in children (MIS-C) is a rare but life-threatening hyperinflammatory condition induced by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes pediatric COVID-19 (pCOVID-19). The ... ...

    Abstract Multisystem inflammatory syndrome in children (MIS-C) is a rare but life-threatening hyperinflammatory condition induced by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes pediatric COVID-19 (pCOVID-19). The relationship of the systemic tissue injury to the pathophysiology of MIS-C is poorly defined. We leveraged the high sensitivity of epigenomics analyses of plasma cell-free DNA (cfDNA) and plasma cytokine measurements to identify the spectrum of tissue injury and glean mechanistic insights. Compared with pediatric healthy controls (pHCs) and patients with pCOVID-19, patients with MIS-C had higher levels of cfDNA primarily derived from innate immune cells, megakaryocyte-erythroid precursor cells, and nonhematopoietic tissues such as hepatocytes, cardiac myocytes, and kidney cells. Nonhematopoietic tissue cfDNA levels demonstrated significant interindividual variability, consistent with the heterogenous clinical presentation of MIS-C. In contrast, adaptive immune cell-derived cfDNA levels were comparable in MIS-C and pCOVID-19 patients. Indeed, the cfDNA of innate immune cells in patients with MIS-C correlated with the levels of innate immune inflammatory cytokines and nonhematopoietic tissue-derived cfDNA, suggesting a primarily innate immunity-mediated response to account for the multisystem pathology. These data provide insight into the pathogenesis of MIS-C and support the value of cfDNA as a sensitive biomarker to map tissue injury in MIS-C and likely other multiorgan inflammatory conditions.
    MeSH term(s) Humans ; Child ; COVID-19/genetics ; SARS-CoV-2 ; Cell-Free Nucleic Acids/genetics ; Cytokines
    Chemical Substances Cell-Free Nucleic Acids ; Cytokines
    Language English
    Publishing date 2023-11-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI171729
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  5. Article ; Online: Clinical features and allograft failure rates of pulmonary antibody-mediated rejection categories.

    Charya, Ananth V / Ponor, Ileana L / Cochrane, Adam / Levine, Deborah / Philogene, Mary / Fu, Yi-Ping / Jang, Moon K / Kong, Hyesik / Shah, Pali / Bon, Ann Mary / Krishnan, Aravind / Mathew, Joby / Luikart, Helen / Khush, Kiran K / Berry, Gerald / Marboe, Charles / Iacono, Aldo / Orens, Jonathan B / Nathan, Steven D /
    Agbor-Enoh, Sean

    The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation

    2022  Volume 42, Issue 2, Page(s) 226–235

    Abstract: Background: Pulmonary antibody-mediated rejection (AMR) consensus criteria categorize AMR by diagnostic certainty. This study aims to define the clinical features and associated outcomes of these recently defined AMR categories.: Methods: ... ...

    Abstract Background: Pulmonary antibody-mediated rejection (AMR) consensus criteria categorize AMR by diagnostic certainty. This study aims to define the clinical features and associated outcomes of these recently defined AMR categories.
    Methods: Adjudication committees reviewed clinical data of 335 lung transplant recipients to define clinical or subclinical AMR based on the presence of allograft dysfunction, and the primary endpoints, time from transplant to allograft failure, a composite endpoint of chronic lung allograft dysfunction and/or death. Clinical AMR was subcategorized based on diagnostic certainty as definite, probable or possible AMR if 4, 3, or 2 characteristic features were present, respectively. Allograft injury was assessed via plasma donor-derived cell-free DNA (ddcfDNA). Risk of allograft failure and allograft injury was compared for AMR categories using regression models.
    Results: Over the 38.5 months follow-up, 28.7% of subjects developed clinical AMR (n = 96), 18.5% developed subclinical AMR (n = 62) or 58.3% were no AMR (n = 177). Clinical AMR showed higher risk of allograft failure and ddcfDNA levels compared to subclinical or no AMR. Clinical AMR included definite/probable (n = 21) or possible AMR (n = 75). These subcategories showed similar clinical characteristics, ddcfDNA levels, and risk of allograft failure. However, definite/probable AMR showed greater measures of AMR severity, including degree of allograft dysfunction and risk of death compared to possible AMR.
    Conclusions: Clinical AMR showed greater risk of allograft failure than subclinical AMR or no AMR. Subcategorization of clinical AMR based on diagnostic certainty correlated with AMR severity and risk of death, but not with the risk of allograft failure.
    MeSH term(s) Humans ; Antibodies ; Transplantation, Homologous ; Lung Transplantation ; Lung ; Allografts ; Graft Rejection/diagnosis
    Chemical Substances Antibodies
    Language English
    Publishing date 2022-09-20
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Intramural
    ZDB-ID 1062522-7
    ISSN 1557-3117 ; 1053-2498
    ISSN (online) 1557-3117
    ISSN 1053-2498
    DOI 10.1016/j.healun.2022.09.012
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  6. Article ; Online: Higher levels of allograft injury in black patients early after heart transplantation.

    Doshi, Amar / Shah, Keyur B / Agbor-Enoh, Sean / Tushak, Zackary / Garcia, Victoria / Kong, Hyesik / Jang, Moon K / Hsu, Steven / Feller, Erika D / Rodrigo, Maria E / Najjar, Samer S / Tunc, Ilker / Yang, Yanqin / Lee, Seiyon / Solomon, Michael A / Berry, Gerald / Marboe, Charles / Shah, Palak / Valantine, Hannah A

    The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation

    2021  Volume 41, Issue 7, Page(s) 855–858

    Abstract: Black patients suffer higher rates of antibody-mediated rejection and have worse long-term graft survival after heart transplantation. Donor-derived cell free DNA (ddcfDNA) is released into the blood following allograft injury. This study analyzed % ... ...

    Abstract Black patients suffer higher rates of antibody-mediated rejection and have worse long-term graft survival after heart transplantation. Donor-derived cell free DNA (ddcfDNA) is released into the blood following allograft injury. This study analyzed %ddcfDNA in 63 heart transplant recipients categorized by Black and non-Black race, during the first 200 days after transplant. Immediately after transplant, %ddcfDNA was higher for Black patients (mean [SE]: 8.3% [1.3%] vs 3.2% [1.2%], p = 0.001). In the first week post-transplant, the rate of decay in %ddcfDNA was similar (0.7% [0.68] vs 0.7% [0.11], p = 0.78), and values declined in both groups to a comparable plateau at 7 days post-transplant (0.46% [0.03] vs 0.45% [0.04], p = 0.78). The proportion of Black patients experiencing AMR was higher than non-Black patients (21% vs 9% [hazard ratio of 2.61 [95% confidence interval: 0.651-10.43], p = 0.18). Black patients were more likely to receive a race mismatched organ than non-Black patients (69% vs 35%, p = 0.01), which may explain the higher levels of early allograft injury.
    MeSH term(s) Allografts ; Graft Rejection/epidemiology ; Graft Survival ; Heart Transplantation ; Humans ; Tissue Donors ; Transplantation, Homologous
    Language English
    Publishing date 2021-12-23
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
    ZDB-ID 1062522-7
    ISSN 1557-3117 ; 1053-2498
    ISSN (online) 1557-3117
    ISSN 1053-2498
    DOI 10.1016/j.healun.2021.12.006
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

To top