Article
Multidisciplinary Sciences
Ji Lei, Maria M. Coronel, Esma S. Yolcu, Hongping Deng, Orlando Grimany-Nuno, Michael D. Hunckler, Vahap Ulker, Zhihong Yang, Kang M. Lee, Alexander Zhang, Hao Luo, Cole W. Peters, Zhongliang Zou, Tao Chen, Zhenjuan Wang, Colleen S. McCoy, Ivy A. Rosales, James F. Markmann, Haval Shirwan, Andres J. Garcia
Summary: We report a strategy of cotransplanting allogeneic islets and streptavidin (SA)-FasL-presenting microgels to the omentum under transient rapamycin monotherapy, which resulted in robust glycemic control, sustained C-peptide levels, and graft survival in diabetic nonhuman primates. This localized immunomodulatory strategy shows translational potential in beta cell replacement for treating type 1 diabetes.
Article
Cell Biology
Reem Alkhayer, Viviane Ponath, Miriam Frech, Till Adhikary, Johannes Graumann, Andreas Neubauer, Elke Pogge von Strandmann
Summary: This study identifies the transcription factor KLF4 as associated with the MICA promoter, and demonstrates that pharmacological activation of KLF4 leads to increased expression of MICA in AML cells. The small compound APTO253, which activates KLF4, also inhibits MYC expression and causes DNA damage in AML cells. The induction of MICA expression renders AML cells more susceptible to NK cell-mediated killing, suggesting a potential therapeutic approach for targeting AML cells.
CELL COMMUNICATION AND SIGNALING
(2023)
Article
Cardiac & Cardiovascular Systems
Richard C. Daly, Andrew N. Rosenbaum, Joseph A. Dearani, Alfredo L. Clavell, Naveen L. Pereira, Barry A. Boilson, Robert P. Frantz, Atta Behfar, Shannon M. Dunlay, Richard J. Rodeheffer, John A. Schirger, Timucin Taner, Manish J. Gandhi, Julie K. Heimbach, Charles B. Rosen, Brooks S. Edwards, Sudhir S. Kushwaha
Summary: This study demonstrates the successful transplantation using a heart-after-liver transplantation protocol, which provides profound immunologic protection and prevents adverse immunological outcomes in highly sensitized patients requiring combined heart-liver transplantation. The results show near-elimination of donor specific antibodies and minimal rejection episodes, leading to favorable long-term patient and graft outcomes.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Philip F. Halloran, Katelynn Madill-Thomsen, Arezu Z. Aliabadi-Zuckermann, Martin Cadeiras, Marisa G. Crespo-Leiro, Eugene C. Depasquale, Mario Deng, Johannes Gokler, Daniel H. Kim, Jon Kobashigawa, Peter Macdonald, Luciano Potena, Keyur Shah, Josef Stehlik, Andreas Zuckermann
Summary: This study extended the MMDx system to classify heart transplant endomyocardial biopsies into a new Minor category characterized by low-level inflammation and ABMR-related gene expression. The results suggest that low-level ABMR-related molecular stress may be operating in more hearts than previously estimated.
JOURNAL OF HEART AND LUNG TRANSPLANTATION
(2022)
Article
Hematology
Pedro Henrique Alves da Silva, Samantha Xing, Andriana G. Kotini, Eirini P. Papapetrou, Xiaoyu Song, Kai W. Wucherpfennig, John Mascarenhas, Lucas Ferrari de Andrade
Summary: The MICA/B antibody 7C6 effectively inhibits the growth of Acute myeloid leukemia (AML) and triggers macrophage-dependent phagocytosis of AML cells. Romidepsin, a selective histone deacetylase inhibitor, increases MICB mRNA in AML cells and stabilizes the translated protein by 7C6. The combination of 7C6 and romidepsin promotes macrophage-driven immunity against AML, leading to a reduction in leukemia burden. These findings provide the rationale for clinical testing of this combination therapy for AML treatment.
Article
Surgery
Taichi Kanzawa, Daisuke Tokita, Kan Saiga, Takafumi Yamakawa, Hidetoshi Ishigooka, Hironori Fukuda, Haruki Katsumata, Satoshi Miyairi, Rumi Ishii, Toshihito Hirai, Toshio Imai, Masayoshi Okumi, Kazunari Tanabe
Summary: This study demonstrated the importance of the FKN-CX3CR1 axis in ischemia reperfusion injury-related rejection. Blocking this axis could potentially improve transplantation outcomes.
TRANSPLANT INTERNATIONAL
(2022)
Article
Immunology
Ute Saunders, Mao Li, Srinivasa R. Boddeda, Sonya Maher, Jessica Ghere, Irina Kaptsan, Ravi Dhital, Victoria Velazquez, Lingling Guo, Bo Chen, Qiang Zeng, Trenton R. Schoeb, Rachel Cianciolo, Masako Shimamura
Summary: This study found that complement-fixing antibodies can deposit into MCMV-infected renal allografts, leading to tissue damage and potentially induce cytotoxic effects on renal tubular epithelial cells.
Article
Immunology
Yi Chen, Wenmin Zhang, Hui Bao, Wubing He, Lihong Chen
Summary: The study found that HMGB1 expression is upregulated in liver allografts during acute rejection, leading to increased inflammatory cell infiltration and DC maturation, ultimately promoting T cell proliferation and differentiation. Inhibition of HMGB1 with glycyrrhizic acid during liver preservation was shown to reduce inflammation, hepatocyte damage, and prolong allograft survival time, suggesting a potential therapeutic target to prevent acute rejection in liver transplantation.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Xiaoxiao Du, Weitao Que, Xin Hu, Xiao Yu, Wen-Zhi Guo, Shuijun Zhang, Xiao-Kang Li
Summary: Oridonin has the potential to prolong the survival of completely mismatched cardiac allografts in vivo and improve transplant tolerance by inhibiting the NF-kappa B/NLRP3 signaling pathway, reducing IL-1 beta and IL-18 production, suppressing Th1 cell differentiation and proliferation, and expanding regulatory T cell populations.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Edward J. Filippone, John L. Farber
Summary: T cell-mediated rejection (TCMR) is a common cause of kidney allograft loss and can be indirect or direct. Banff defined acute TCMR should be treated with antirejection therapy and maintenance immunosuppression. Isolated interstitial inflammation or tubulitis does not require treatment. Gene expression analysis can assist in diagnosis. Borderline lesions may require treatment and close follow-up. Surveillance protocol biopsies and blood-borne assays are useful for monitoring stable patients. Treatment for acute TCMR involves corticosteroids with lymphocyte depleting antibodies. The optimal treatment for chronic active TCMR is uncertain and requires further trials.
Article
Medicine, General & Internal
Reuben D. Sarwal, Wanzin Yazar, Nicholas Titzler, Jeremy Wong, Chih-hung Lai, Christopher Chin, Danielle Krieger, Jeff Stoll, Francisco Dias Lourenco, Minnie M. Sarwal, Srinka Ghosh
Summary: The development of QSant has become necessary due to the suboptimal sensitivity and specificity of current allograft monitoring methodologies. Q-Score enables prediction of injury and rejection risk, capturing the trajectory of rejection through changes in the score. The clinical utility of QSant in early diagnosis of allograft injury and rejection across the alloimmunity gradient of 32-100 is explored in this publication.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Medicine, General & Internal
Dmitry Rychkov, Swastika Sur, Marina Sirota, Minnie M. Sarwal
Summary: This prognostic study utilized public kidney transplant data to develop an Instability Score based on gene expression data, which identified immune heterogeneity in histologically stable kidney allografts. The findings suggest that integrating the Instability Score into clinical care could improve the accuracy of estimating patient clinical outcomes.
Article
Pathology
Hidetoshi Tsuda, Nina Dvorina, Karen S. Keslar, Jessica Nevarez-Mejia, Nicole M. Valenzuela, Elaine F. Reed, Robert L. Fairchild, William M. Baldwin
Summary: This article reports a novel model for studying antibody-mediated cardiac allograft vasculopathy (CAV) after heart transplantation. By decreasing T-cell-mediated graft injury and promoting antibody-mediated injury, the transplant developed CAV with intense C4d deposition and macrophage infiltration, revealing key molecular mechanisms involved in the pathology.
AMERICAN JOURNAL OF PATHOLOGY
(2022)
Article
Respiratory System
Tomoyuki Nakagiri, Sabine Wrenger, Kokilavani Sivaraman, Fabio Ius, Tobias Goecke, Patrick Zardo, Veronika Grau, Tobias Welte, Axel Haverich, Ann-Kathrin Knofel, Sabina Janciauskiene
Summary: Therapy with AAT suppresses acute rejection after LuTx in a mouse model, with beneficial effects involving anti-protease and immunomodulatory activities of AAT.
RESPIRATORY RESEARCH
(2021)
Article
Multidisciplinary Sciences
Yuta Asano, Joe Daccache, Dharmendra Jain, Kichul Ko, Andrew Kinloch, Margaret Veselits, Donald Wolfgeher, Anthony Chang, Michelle Josephson, Patrick Cunningham, Anat Tambur, Aly A. Khan, Shiv Pillai, Anita S. Chong, Marcus R. Clark
Summary: Intrarenal B cells in human renal allografts are indicative of poor prognosis and may be innate B cells reactive to renal-specific or inflammation-associated antigens, leading to rejection. The authors used single cell RNA sequencing to investigate this relationship and found evidence supporting this hypothesis.
NATURE COMMUNICATIONS
(2021)