Article
Immunology
Min Liu, Xiaolei Luo, Qin Xu, Hongbiao Yu, Linbo Gao, Rong Zhou, Tao Wang
Summary: The study found that levels of adipsin, C5a, and sENG were significantly increased in the plasma of pregnant women with preeclampsia before delivery. In healthy pregnant women, levels of adipsin, C5a, and sENG increased from the third trimester and remained stable postpartum, but C3a levels increased in the second trimester and remained stable afterward.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Fernando Corvillo, Laura Gonzalez-Sanchez, Alberto Lopez-Lera, Emilia Arjona, Giovanni Ceccarini, Ferruccio Santini, David Araujo-Vilar, Rebecca J. Brown, Joan Villarroya, Francesc Villarroya, Santiago Rodriguez de Cordoba, Teresa Caballero, Pilar Nozal, Margarita Lopez-Trascasa
Summary: The study found significantly elevated FD levels in BSS patients, with a strong positive correlation between FD and age in BSS. While a positive correlation between FD and C3 was seen in C3G patients, no correlation was detected in BSS. Gene expression studies in BSS adipose tissue showed decreased CFD and C3 levels but elevated C5 transcript levels. This suggests that FD may serve as a reliable diagnostic biomarker for the pathophysiology of BSS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Immunology
Jonathan Barratt, Ilene Weitz
Summary: The complement system is crucial for defending against pathogens, but dysregulation can lead to autoimmune diseases. The alternative complement pathway plays a key role in amplifying activation. Factor D, a serine protease in this pathway, is essential for C3 convertase formation and is a potential therapeutic target for diseases involving excessive complement activation.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Margrethe Flesvig Holt, Annika E. Michelsen, Negar Shahini, Elisabeth Bjorkelund, Christina Holt Bendz, Richard J. Massey, Camilla Schjalm, Bente Halvorsen, Kaspar Broch, Thor Ueland, Lars Gullestad, Per H. Nilsson, Pal Aukrust, Tom Eirik Mollnes, Mieke C. Louwe
Summary: In patients with heart failure, the alternative pathway of the complement system is activated, but not the terminal pathway. Plasma levels of factor B and C3 convertase C3bBbP are elevated in these patients, but not associated with mortality during follow-up.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Wanrong Man, Xinglong Song, Zhenyu Xiong, Jing Gu, Jie Lin, Xiaoming Gu, Duan Yu, Congye Li, Mengyuan Jiang, Xuebin Zhang, Zhi Yang, Yang Cao, Yan Zhang, Xiaofei Shu, Dexi Wu, Haichang Wang, Gang Ji, Dongdong Sun
Summary: This study reveals the important role of Adipsin in cardiovascular diseases, demonstrating its ability to protect cardiomyocytes against ferroptosis and maintain iron homeostasis. The efficient delivery of Adipsin to the heart through exosomes suggests a promising therapeutic strategy to prevent adverse cardiac remodeling following ischemic heart injury.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Review
Immunology
Anna Schubart, Stefanie Flohr, Tobias Junt, Joerg Eder
Summary: Dysregulation of the alternative complement pathway can lead to various diseases, and inhibitors targeting central proteases of the pathway are being developed as therapeutics. These inhibitors have the potential to treat complement-mediated diseases in both systemic and peripheral tissues, and may also be effective in inhibiting complement activation in the central nervous system.
IMMUNOLOGICAL REVIEWS
(2023)
Review
Immunology
Jutamas Shaughnessy, Aleyo Chabeda, Lisa A. Lewis, Sanjay Ram
Summary: The alternative pathway (AP) is an ancient part of the complement system that marks pathogens for elimination by phagocytes. Pathogens have evolved various mechanisms to evade the complement system, such as degrading AP proteins or blocking C3 convertase function. Many microbes recruit the AP inhibitor factor H (FH) by mimicking FH interactions with host cells.
IMMUNOLOGICAL REVIEWS
(2023)
Article
Immunology
Francesca Granata, Lorena Duca, Valentina Brancaleoni, Silvia Fustinoni, Giacomo De Luca, Irene Motta, Giovanna Graziadei, Elena Di Pierro
Summary: The study found that levels of CS proteins in patients with protoporphyria were higher than the control group in both summer and winter, with a more significant increase in summer. The main factors of the AP increased over the season, confirming the involvement of the AP in relation to light exposure. The systemic response could justify the general malaise of patients after long light exposure.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Erica Daina, Monica Cortinovis, Giuseppe Remuzzi
Summary: Dysregulation and accelerated activation of the alternative pathway of complement play important roles in kidney diseases, and complement-directed therapies have shown potential for treatment. Although there have been successful cases, incorporating these therapies into clinical practice still faces challenges.
IMMUNOLOGICAL REVIEWS
(2023)
Article
Immunology
Alexandra Gerogianni, Jordan D. Dimitrov, Alessandra Zarantonello, Victoria Poillerat, Satheesh Chonat, Kerstin Sandholm, Karin E. McAdam, Kristina N. Ekdahl, Tom E. Mollnes, Camilla Mohlin, Lubka T. Roumenina, Per H. Nilsson
Summary: Hemolysis leads to an excess of cell-free heme and consumption of heme-scavenger proteins, which is linked to the activation of the inflammatory system. This study investigates the influence of heme on the regulatory function of the complement system and finds that heme promotes uncontrolled amplification of the complement alternative pathway by interfering with factor I's regulatory capacity. Reduced levels of heme-scavenger proteins and heme-scavenger protein-factor I complexes during hemolytic crisis increase the risk of heme-mediated factor I inhibition.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Emma Ispasanie, Lukas Muri, Anna Schubart, Christine Thorburn, Natasa Zamurovic, Thomas Holbro, Michael Kammuller, Gerd Pluschke
Summary: The study examined the protective effect of vaccination against invasive meningococcal disease in patients treated with alternative pathway inhibitors. The findings suggest that while alternative pathway inhibitors can impact the killing of meningococci, vaccination can still provide protection against invasive disease.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Federica Defendi, Corentin Leroy, Olivier Epaulard, Giovanna Clavarino, Antoine Vilotitch, Marion Le Marechal, Marie-Christine Jacob, Tatiana Raskovalova, Martine Pernollet, Audrey Le Gouellec, Jean-Luc Bosson, Pascal Poignard, Matthieu Roustit, Nicole Thielens, Chantal Dumestre-Perard, Jean-Yves Cesbron
Summary: The study analyzed the complement activation pathways and components in COVID-19 patients, identifying two distinct patient clusters: one with activation of alternative and lectin pathways, low antigenic levels of complement components, and higher mortality and need for oxygen or ICU care; the other with high classical pathway activity, higher antigenic levels of complement components, lower need for ICU care, and no deaths.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Janina Niederreiter, Christine Eck, Tajana Ries, Arndt Hartmann, Bruno Maerkl, Maike Buettner-Herold, Kerstin Amann, Christoph Daniel
Summary: Complement deposition is increased in the lungs and kidneys of critically ill COVID-19 patients, suggesting its involvement in exacerbating the inflammatory response.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Binshan Zhang, Guolan Xing
Summary: This study found that TMA is an independent risk factor for renal survival in LN patients, and the activation of complement lectin pathway and alternative pathway are involved in the pathogenesis of LN-associated TMA.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Ziwan Ji, Zhongming Cai, Shuming Gu, Yucang He, Zikai Zhang, Tian Li, Qing Wei, Jingping Wang, Chen Ke, Liqun Li
Summary: The study found that adipose-derived exosomes (ADEs) can inhibit adipogenic differentiation of adipose-derived stem cells by activating the Hedgehog (Hh) signaling pathway, thereby reducing the adverse effects of obesity on wound healing.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2021)
Review
Medicine, Research & Experimental
Anuja Java, Anthony J. Apicelli, M. Kathryn Liszewski, Ariella Coler-Reilly, John P. Atkinson, Alfred H. J. Kim, Hrishikesh S. Kulkarni
Article
Obstetrics & Gynecology
A. Lokki, L. Teirila, M. Triebwasser, E. Daly, A. Bhattacharjee, L. Uotila, M. Llort Asens, M. Kurki, M. Perola, K. Auro, J. E. Salmon, M. Daly, J. P. Atkinson, H. Laivuori, S. Fagerholm, S. Meri, Finnpec
Summary: This study investigated genetic variants in complement receptors CR3 and CR4 in relation to pre-eclampsia and found that changes in complement-facilitated phagocytosis are associated with the disease. Further research is needed to determine if aberrant activity of CR3 and CR4 leads to altered immune responses in individuals carrying these variants, and their role in pre-eclampsia pathogenesis.
BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY
(2021)
Article
Biochemistry & Molecular Biology
O. McMahon, T. M. Hallam, S. Patel, C. L. Harris, A. Menny, W. M. Zelek, R. Widjajahakim, A. Java, T. E. Cox, N. Tzoumas, D. H. W. Steel, V. G. Shuttleworth, K. Smith-Jackson, V Brocklebank, H. Griffiths, A. J. Cree, J. P. Atkinson, A. J. Lotery, D. Bubeck, B. P. Morgan, K. J. Marchbank, J. M. Seddon, D. Kavanagh
Summary: Age-related macular degeneration is a complex neurodegenerative eye disease leading to irreversible vision loss among elderly Caucasians. Genetic variants in the complement pathway play a significant role in the disease, with the rare C9 P167S variant associated with low plasma levels of C9 and increased polymerization and hemolytic activity. This finding provides a basis for gene therapy trials targeting the terminal pathway of complement in AMD.
HUMAN MOLECULAR GENETICS
(2021)
Article
Rheumatology
Xin Duan, Lei Cai, Christine T. N. Pham, Yousef Abu-Amer, Hua Pan, Robert H. Brophy, Samuel A. Wickline, Muhammad Farooq Rai
Summary: IA delivery of a periostin-siRNA nanocomplex successfully inhibited periostin expression in posttraumatic OA in mice and reduced cartilage damage severity. Mechanistically, it was found that periostin-induced MMP-13 expression was abolished by SC-514, indicating a link between periostin and NF-kappa B.
ARTHRITIS & RHEUMATOLOGY
(2021)
Review
Virology
Romchat Kraivong, Nuntaya Punyadee, M. Kathryn Liszewski, John P. Atkinson, Panisadee Avirutnan
Summary: Dengue is a mosquito-borne viral disease that can lead to significant health and economic burdens globally. The dengue virus has four serotypes, with primary infections often being asymptomatic or causing mild symptoms, while secondary infections with a different serotype can result in severe disease. The complement system and lectin pathway play key roles in the pathogenesis of dengue, with differences in viral glycan recognition influencing the efficiency of virus binding and neutralization.
Article
Multidisciplinary Sciences
Yun-Rak Choi, Kelsey H. Collins, Luke E. Springer, Lara Pferdehirt, Alison K. Ross, Chia-Lung Wu, Franklin T. Moutos, Natalia S. Harasymowicz, Jonathan M. Brunger, Christine T. N. Pham, Farshid Guilak
Summary: By using CRISPR-Cas9 genome editing and tissue engineering, a synthetic gene circuit has been created in cells that can trigger a specific therapeutic response based on changing levels of inflammatory cytokines. These bioengineered implants demonstrate rapid activation and recovery in vitro or in vivo, and show significant anti-inflammatory effects. This combination application offers new possibilities for treating chronic diseases.
Review
Immunology
M. Kathryn Liszewski, John P. Atkinson
Summary: Membrane cofactor protein CD46 plays a crucial role as a complement regulatory protein, but also functions in human reproduction, autophagy, T cell modulation, and as a receptor for pathogens. Deficiencies in CD46 contribute to inflammatory disorders, while its overexpression in cancers and as a receptor for viruses has implications in targeted therapies.
CURRENT OPINION IN IMMUNOLOGY
(2021)
Article
Chemistry, Physical
Megan S. Michie, Baogang Xu, Gail Sudlow, Luke E. Springer, Christine T. N. Pham, Samuel Achilefu
Summary: In this study, NIR dye-peptide conjugates were synthesized and it was found that a peptide-driven strategy can alter the aggregation states of molecular probes in aqueous solutions, leading to effective imaging of inflammatory arthritis joints. The results suggest that peptide plays a dominant role in controlling the photophysical properties of these bioconjugates.
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY A-CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Qingyu Zhou, Justin Doherty, Antonina Akk, Luke E. Springer, Ping Fan, Ivan Spasojevic, Ganesh V. Halade, Huanghe Yang, Christine T. N. Pham, Samuel A. Wickline, Hua Pan
Summary: In this study, the potential of rapamycin perfluorocarbon (PFC) nanoparticles to mitigate cisplatin-induced acute kidney injury was demonstrated with a single preventative dose. The pharmacokinetics and biodistribution of rapamycin were improved by the PFC nanoparticle delivery system. The safety of rapamycin PFC nanoparticles was also confirmed in both in vitro and in vivo experiments.
Article
Medicine, General & Internal
Zhen Ren, Stephen J. Perkins, Latisha Love-Gregory, John P. Atkinson, Anuja Java
Summary: Genetic testing in a kidney transplant cohort revealed rare variants in complement proteins associated with TMA and C3G, with approximately 50% classified as variants of uncertain significance. Structural and functional analysis of identified variants in complement factor H were conducted, determining both deleterious and normal functional activity. The study highlights the importance of functional analysis of genetic variants in complex clinicopathologic scenarios, providing insights for clinical decision making after kidney transplantation.
FRONTIERS IN MEDICINE
(2021)
Letter
Biophysics
Sonia Elhadad, Amy Chadburn, Cynthia Magro, Koen Van Besien, Elisha D. O. Roberson, John P. Atkinson, Hunter Terry, June Greenberg, Whitney Reid, John Chapin, Dennis Copertino, Sahar Geramfard, Lizamarie Bachier Rodriguez, Nina Orfali, Usama Gerghis, Tsiporah Shore, Sebastian Mayer, Jasimuddin Ahamed, Jeffrey Laurence
BONE MARROW TRANSPLANTATION
(2022)
Review
Immunology
M. Kathryn Liszewski, John P. Atkinson
Summary: The alternative pathway (AP) is an important immune response mechanism, but its amplification and sustained activation may lead to diseases and harm human health. Genetic factors related to complement and chronic inflammatory processes are found to be associated with many diseases. Therefore, understanding the alternative pathway and developing novel therapeutic approaches is crucial for human health.
IMMUNOLOGICAL REVIEWS
(2023)
Article
Biochemistry & Molecular Biology
Qingyu Zhou, James D. Quirk, Ying Hu, Huimin Yan, Joseph P. Gaut, Christine T. N. Pham, Samuel A. Wickline, Hua Pan
Summary: Researchers have discovered that using rapamycin-loaded perfluorocarbon nanoparticles (PFC NP) can effectively deliver the drug to the injured kidneys, mitigating cisplatin-induced acute kidney injury and preserving renal function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Polymer Science
Kelsey H. H. Collins, Lara Pferdehirt, Leila S. S. Saleh, Alireza Savadipour, Luke E. E. Springer, Kristin L. L. Lenz, Dominic M. M. Thompson Jr, Sara J. J. Oswald, Christine T. N. Pham, Farshid Guilak
Summary: Biologic therapies have greatly changed the treatment options for rheumatoid arthritis, but their long-term use may result in adverse effects. To address this issue, researchers developed induced pluripotent stem cells (iPSCs) that can express an IL-1 inhibitor in response to disease flares. These iPSCs were implanted using subcutaneously injected agarose hydrogels, showing significant therapeutic efficacy in a model of inflammatory arthritis. This minimally invasive cell-based drug delivery strategy has the potential to be used in the treatment of other autoimmune or chronic diseases.
Article
Virology
Jack R. Hemsath, A. Manuel Liaci, Jeffrey D. Rubin, Brian J. Parrett, Shao-Chia Lu, Tien Nguyen, Mallory A. Turner, Christopher Y. Chen, Karolina Cupelli, Vijay S. Reddy, Thilo Stehle, M. Kathryn Liszewski, John P. Atkinson, Michael A. Barry
Summary: This study investigates the usage of CD46 receptor by Ad26 virus in different administration routes and its impact on infection efficiency. The results show that Ad26 can use CD46 as a receptor but its usage varies depending on the administration route. Ectopic expression of CD46 on cells enhances Ad26 infection, while tumor injection or intravenous injection shows lower infection efficiency. High-dose intravenous injection of Ad26 induces liver enzyme release and reduces white blood cell counts but does not cause thrombocytopenia.
JOURNAL OF VIROLOGY
(2022)