Article
Immunology
Eva Karpati, Mariann Kremlitzka, Noemi Sandor, David Hajnal, Andrea E. Schneider, Mihaly Jozsi
Summary: Studies have shown that proteins from the factor H family have diverse effects on monocytes and neutrophils beyond modulating complement activation, altering key immune functions such as cell adhesion and inflammatory cytokine secretion. This suggests that FH-based complement inhibitors may have additional effects that could be utilized in infection protection and vaccine development.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Natalia Ruiz -Molina, Juliana Parsons, Eva L. Decker, Ralf Reski
Summary: Human complement is crucial for defense against pathogens and tissue homeostasis. Factor H (FH) and Factor H-related protein 1 (FHR1) are important complement regulators. The structure of synthetic regulators based on FH and FHR1 were modeled using AlphaFold2, and the interactions between C3 fragments, MAC components (C5, C7, and C9), and various regulators were studied using AlphaFold-Multimer (AFM). The findings provide insights into the molecular mechanisms of complement regulation and can guide the development of complement-based therapies.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Review
Immunology
Sara R. Moore, Smrithi S. Menon, Claudio Cortes, Viviana P. Ferreira
Summary: The complement system plays a crucial role in both innate and adaptive immunity, with three pathways that can be triggered spontaneously or in response to danger. Pathogens often evade this system by hijacking host complement regulators, such as Factor H, to protect themselves from immune attack. Understanding how pathogens interact with complement regulators like Factor H can provide insights into developing treatment strategies to target pathogen evasion mechanisms.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Urology & Nephrology
Brandon Renner, Jennifer Laskowski, Felix Poppelaars, Viviana P. Ferreira, Judith Blaine, Alexandra H. Antonioli, Jonathan P. Hannan, James M. Kovacs, Cees Van Kooten, Zhiying You, Matthew C. Pickering, V. Michael Holers, Joshua M. Thurman
Summary: This study demonstrates that the Factor H-related proteins have unique effects on different cell types within the kidney, with FHR E causing glomerular complement dysregulation in vivo. This has important implications for understanding the pathogenesis of glomerular diseases.
KIDNEY INTERNATIONAL
(2022)
Article
Immunology
Ola Kamala, Talat H. Malik, Thomas M. Hallam, Thomas E. Cox, Yi Yang, Falguni Vyas, Saimir Luli, Chloe Connelly, Beth Gibson, Kate Smith-Jackson, Harriet Denton, Isabel Y. Pappworth, Lei Huang, David Kavanagh, Matthew C. Pickering, Kevin J. Marchbank
Summary: The study demonstrated that using a murine version of homodimeric mini-FH for treating C3G in murine models showed higher affinity and avidity, as well as enhanced complement regulatory function. Delivery of mini-FH constructs through gene therapy can enhance complement regulation in vivo, supporting its application as a novel treatment strategy for diseases like C3G.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Engineering, Biomedical
Clement Bechtler, Sophia Koutsogiannaki, Ekaterina Umnyakova, Amal Hamid, Avneesh Gautam, Yiannis Sarigiannis, Richard B. Pouw, Christina Lamers, Said Rabbani, Christoph Q. Schmidt, John D. Lambris, Daniel Ricklin
Summary: The use of biomaterials in modern medicine has advanced drug delivery strategies and reduced morbidity and mortality. However, immune reactions remain a serious complication.
ACTA BIOMATERIALIA
(2023)
Article
Immunology
Markus A. Loeven, Marissa L. Maciej-Hulme, Cansu Yanginlar, Melanie C. Hubers, Edwin Kellenbach, Mark de Graaf, Toin H. van Kuppevelt, Jack Wetzels, Ton J. Rabelink, Richard J. H. Smith, Johan van der Vlag
Summary: Complement dysregulation is a key characteristic of renal diseases like aHUS and C3G, where mutations in proteins like FH and FHRs can lead to complement activation. This study found that 2-O-desulfated heparin derivatives could potentially serve as therapeutics for dysregulated complement diseases by competitively inhibiting FHR1 and FHR5 binding to HSGlx, reducing C3b deposition.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Ophthalmology
Robyn M. Biggs, Elisavet Makou, Scott Lauder, Andrew P. Herbert, Paul N. Barlow, Suresh K. Katti
Summary: This study compares the functional differences between a control version of Factor H (FH) and 21 macular degeneration-associated FH variants. The results show minimal functional differences in some variants, while others underperform. The study also identifies two potentially pathogenic variants located in the center of the molecule.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Article
Immunology
Wei Tang, Hongyang Liu, Lixian Chen, Ke Zhao, Yaoyao Zhang, Ke Zheng, Cheng Zhu, Tiansheng Zheng, Jiahong Liu, Dandan Wang, Lingfang Yu, Xinyu Fang, Chen Zhang, Kuan-Pin Su
Summary: The study revealed that patients with anhedonia in major depressive disorder exhibit different inflammatory characteristics compared to patients without anhedonia. Elevated plasma CFH levels may serve as a potential biomarker for anhedonia in subtyping MDD.
BRAIN BEHAVIOR AND IMMUNITY
(2021)
Article
Immunology
Alexandra Gerogianni, Laura M. Baas, Dick J. Sjostrom, Nicole C. A. J. van de Kar, Marit Pullen, Siem J. van de Peppel, Per H. Nilsson, Lambertus P. van den Heuvel
Summary: This study evaluated the functional impact of eight recombinant FI genetic variants found in patients. The results demonstrated that mutations in the FIMAC and SP domains significantly reduced FI's protease activity, while mutations in the LDLRA2 domain did not have a profound effect. Different analytical assays showed a strong positive correlation, and combining different methods and co-factors was necessary to observe activity differences in certain genetic variants.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Douwe Jan Dijkstra, A. Inkeri Lokki, Lobke Marijn Gierman, Nicole Veronique Borggreven, Carin van der Keur, Michael Eikmans, Kyra Andrea Gelderman, Hannele Laivuori, Ann-Charlotte FINNPEC Core Investigator Grp, Ann-Charlotte Iversen, Marie-Louise P. van der Hoorn, Leendert Adrianus Trouw
Summary: Preeclampsia (PE) may be associated with decreased levels of C1q and FH, which are related to placental dysfunction and immune response.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Genetics & Heredity
Yuka Sugawara, Hideki Kato, Masao Nagasaki, Yoko Yoshida, Madoka Fujisawa, Naoko Minegishi, Masayuki Yamamoto, Masaomi Nangaku
Summary: We identified two aHUS patients with no CFH antibodies or causative variants of aHUS-related genes, but their plasma showed increased hemolysis levels, suggesting CFH-related abnormalities. CNV analysis revealed CFH-CFHR1 hybrid genes in these patients. Our study highlights the importance of integrated analysis based on clinical examination, functional analysis, and detailed genetic investigation for suspected aHUS patients.
JOURNAL OF HUMAN GENETICS
(2023)
Review
Pharmacology & Pharmacy
Christine Skerka, Gabriele Pradel, Luke D. Halder, Peter F. Zipfel, Svante L. H. Zipfel, Olaf Strauss
Summary: FHR-1, a member of the factor H protein family, plays a crucial role in regulating innate immune complement reactions. Recent studies have shown its involvement in various diseases and potential role in inflammation induced by necrosis. This review provides insights into the role of FHR-1 in pathology and identifies it as a potential therapeutic target for inflammatory diseases.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Review
Immunology
Felix Poppelaars, Elena Goicoechea de Jorge, Ilse Jongerius, Antje J. Baeumner, Mark-Steven Steiner, Mihaly Jozsi, Erik J. M. Toonen, Diana Pauly
Summary: The human Factor H (FH) family is linked to various diseases, with controversies and discrepancies in its functional roles and quantification, requiring interdisciplinary collaboration to address these challenges.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Ashley L. Marcinkiewicz, Kalvis Brangulis, Alan P. Dupuis, Thomas M. Hart, Maxime Zamba -Campero, Tristan A. Nowak, Jessica L. Stout, Inara Akopjana, Andris Kazaks, Janis Bogans, Alexander T. Ciota, Peter Kraiczy, Sergios-Orestis Kolokotronis, Yi-Pin Lin
Summary: Modern infectious disease outbreaks often involve changes in host tropism. The Lyme disease-causing bacterium Bb is an ideal model to investigate the molecular mechanisms of host tropism. Our research shows that minor sequence variation in the bacterial outer surface protein CspZ may confer dramatic differences in host-specific infectivity. We also identified the evolutionary mechanisms driving host tropism emergence.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Immunology
Amit Nair, Laia Coromina Hernandez, Shimul Shah, Xaralambos Zervos, Michael Zimmerman, Kazunari Sasaki, Teresa Diago, Koji Hashimoto, Masato Fujiki, Federico Aucejo, Jessica Bollinger, Tiffany L. Kaiser, Charles M. Miller, Cristiano Quintini, John J. Fung, Bijan Eghtesad
Summary: In liver transplantation, delaying the initiation of calcineurin inhibitors (CNI) and using induction rabbit antithymocyte globulin (rATG) may help preserve early kidney function, especially when CNI initiation is delayed beyond 10 days or target tacrolimus levels are lower.
Article
Surgery
Angelica Perez-Gutierrez, Umar Siddiqi, Gene Kim, Govind Rangrass, Aalok Kacha, Valluvan Jeevanandam, Yolanda Becker, Lisa Potter, John Fung, Talia B. Baker
Summary: This paper presents the best practices for successful execution of combined heart-liver-kidney transplantation, including patient selection, perioperative planning, and coordination among transplant teams. By careful selection and collaboration, this highly challenging operation can be successfully performed.
CLINICAL TRANSPLANTATION
(2022)
Article
Immunology
Omar K. Jamil, Burhaneddin Sandikci, Nolan Faust, Thomas G. Cotter, Sonali Paul, Diego di Sabato, John Fung, Michael Charlton
Summary: NASH has become a more frequent indication for liver transplantation, but patients with NASH have poorer long-term outcomes compared to other indications, especially for those undergoing simultaneous liver kidney transplantation.
Editorial Material
Gastroenterology & Hepatology
John Fung, Diego DiSabato, Chih-Yi Liao, Osmanuddin Ahmed, Anjana Pillai
HEPATOBILIARY & PANCREATIC DISEASES INTERNATIONAL
(2023)
Article
Oncology
Aditya Juloori, Rohan R. Katipally, Jeffrey M. Lemons, Anurag K. Singh, Renuka Iyer, Jared R. Robbins, Ben George, William A. Hall, Sean P. Pitroda, Fauzia Arif, John Fung, Anjana Pillai, Chih-Yi Liao, Manish Sharma, Stanley L. Liauw
Summary: This study investigated the safety and efficacy of stereotactic body radiation therapy (SBRT) with immunotherapy in patients with hepatocellular carcinoma (HCC). The results showed that the combination of SBRT with nivolumab plus ipilimumab had better survival and efficacy compared to immunotherapy alone in HCC patients, suggesting the need for further investigation.
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Osman Ahmed, Qian Yu, Mikin Patel, Gloria Hwang, Anjana Pillai, Chih-yi Liao, John Fung, Talia Baker
Summary: A combination therapy of yttrium-90 transarterial radioembolization (TARE) and systemic gemcitabine, cisplatin, and capecitabine is safe and effective for the first-line treatment of locally advanced intrahepatic cholangiocarcinoma (iCCA), resulting in high rates of downstaging and favorable overall survival.
JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY
(2023)
Review
Medicine, General & Internal
Kumar Jayant, Thomas G. Cotter, Isabella Reccia, Francesco Virdis, Mauro Podda, Nikolaos Machairas, Ramesh P. Arasaradnam, Diego Di Sabato, John C. LaMattina, Rolf N. Barth, Piotr Witkowski, John J. Fung
Summary: This study compared the outcomes of high-MELD and low-MELD living-donor liver transplant recipients and found no significant differences in patient survival, graft survival, and most complications between the two groups. However, the high-MELD group had a higher risk of pulmonary infection, abdominal fluid collection, and prolonged ICU stay.
JOURNAL OF CLINICAL MEDICINE
(2023)
Meeting Abstract
Immunology
Mateusz Ogledzinski, Piotr J. Bachul, Braden Juengel, Yaser Al-Salmay, Jayant Kumar, Angelica Perez-Gutierrez, Lindsay Basto, Laurencia Perea, Ling-Jia Wang, Martin Tibudan, Rolf Barth, John Fung, Piotr Witkowski
Meeting Abstract
Immunology
Diego Di Sabato, Thomas G. Cotter, Matthew A. Odenwald, Angelica Perez-Gutierrez, Jayant Kumar, Michael Charlton, John Fung
Meeting Abstract
Immunology
Jayant Kumar, Yaser Al-Salmay, Piotr Bachul, John Lamattina, Rolf Barth, John Fung, Diego di Sabato
Meeting Abstract
Immunology
Jayant Kumar, Yaser Al-Salmay, Mauro Podda, Isabella Reccia, Francesco Virdis, Piotr Witkowski, John Lamattina, Rolf Barth, John Fung, Diego Di Sabato, Ramesh Arasadnam
Meeting Abstract
Gastroenterology & Hepatology
Tiffany C. L. Wong, Shirley T. L. Chiu, James Fung, Chung Mau Lo
Meeting Abstract
Surgery
Angelica Perez-Gutierrez, Piotr Bachul, Yaser AlSalmay, Piotr Witkowski, Rolf Barth, Diego DiSabato, John Fung, Yolanda Becker
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Meeting Abstract
Surgery
Piotr Bachul, Angelica Perez-Guetierrez, Yaser Al-Salmay, Braden Juengel, Kumar Jayant, Lindsay Basto, Ling-Jia Wang, Laurencia Perea, Martin Tibudan, Celeste Thomas, Rolf Barth, John Fung, Piotr Witkowski
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Meeting Abstract
Surgery
Angelica Perez-Gutierrez, Thomas Cotter, Mathew Odenwald, Kumar Jayant, Diego DiSabato, Michael Charlton, John Fung
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Article
Engineering, Biomedical
Lin-Lin Luo, Jie Xu, Bing-Qiao Wang, Chen Chen, Xi Chen, Qiu-Mei Hu, Yu-Qiu Wang, Wan-Yun Zhang, Wan-Xiang Jiang, Xin-Ting Li, Hu Zhou, Xiao Xiao, Kai Zhao, Sen Lin
Summary: A novel AAV serotype, AAVYC5, introduced in this study, showed more efficient transduction into multiple retinal layers compared to AAV2, and enabled successful delivery of anti-angiogenic molecules in mice and non-human primates.
