Article
Immunology
Irene Gomez Delgado, Fernando Corvillo, Pilar Nozal, Emilia Arjona, Alvaro Madrid, Marta Melgosa, Juan Bravo, Agnes Szilagyi, Dorottya Csuka, Nora Veszeli, Zoltan Prohaszka, Pilar Sanchez-Corral
Summary: SP-HUS is a clinically well-known disease that may have a worse prognosis than HUS associated with E. coli infections. Studies suggest that risk variants in the CFH-CFHR3-CFHR1 region could contribute to disease-predisposition to SP-HUS, and transient desialylation of complement FH by the pneumococcal neuraminidase may play a role in disease pathogenesis.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Medicine, General & Internal
Mini Michael, Arvind Bagga, Sarah E. Sartain, Richard J. H. Smith
Summary: Haemolytic uraemic syndrome (HUS) is a group of diseases that cause thrombotic microangiopathy, characterized by non-immune microangiopathic haemolytic anaemia, thrombocytopenia, and acute kidney injury. The most common cause of HUS discussed in this review is Shiga toxin-producing Escherichia coli HUS. Identifying the trigger of thrombotic microangiopathy is crucial for personalized treatment. Complement-mediated HUS, once associated with high mortality, can now be treated with anti-complement therapies. However, the high cost of these therapies limits their use in low-income countries.
Review
Medicine, General & Internal
Dan Pugh, Eoin D. O'Sullivan, Fiona Ai Duthie, Philip Masson, David Kavanagh
Summary: AHUS is a rare disorder characterized by abnormal complement regulatory proteins, leading to kidney failure and death in the past. However, new therapies such as terminal complement inhibition show promising outcomes, although based on very low-quality evidence from single-arm studies. Careful consideration of future data is needed for better understanding of treatment duration and adverse outcomes.
COCHRANE DATABASE OF SYSTEMATIC REVIEWS
(2021)
Article
Transplantation
Mendy ter Avest, Romy N. Bouwmeester, Caroline Duineveld, Kioa L. Wijnsma, Elena B. Volokhina, Lambertus P. W. J. van den Heuvel, David M. Burger, Jack F. M. Wetzels, Nicole C. A. J. van de Kar, Rob ter Heine
Summary: This study evaluated the pharmacokinetics and pharmacodynamics of eculizumab in patients with atypical haemolytic uraemic syndrome (aHUS) and proposed improved dosing strategies. The study found that individualized dosing strategy could improve treatment response and reduce treatment costs by prolonging the dosing interval.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2023)
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
Urology & Nephrology
Irene Gomez Delgado, Josue Gutierrez-Tenorio, Gloria M. Fraga Rodriguez, Teresa Cavero, Emilia Arjona, Pilar Sanchez-Corral
Summary: Dysregulation of the alternative complement pathway plays a major role in the pathogenesis of atypical haemolytic uraemic syndrome (aHUS) and membranoproliferative glomerulonephritis (MPGN). Both a 66-year-old male with chronic hepatitis C virus infection and a 5-year-old boy with aHUS carried similar frameshift variants in the complement CFHR5 gene, resulting in reduced levels of factor H-related 5 (FHR-5). Lower FHR-5 levels may predispose individuals to viral and bacterial infections that trigger different renal phenotypes.
CLINICAL KIDNEY JOURNAL
(2021)
Review
Urology & Nephrology
Justo Sandino-Perez, Eduardo Gutierrez, Fernando Caravaca-Fontan, Enrique Morales, Lucia Aubert-Girbal, Ramon Delgado-Lillo, Manuel Praga
Summary: This study identified four cases of HUS following acute pancreatitis, with a mean age of 30 years and all patients being male, primarily due to excessive alcohol consumption. All patients developed progressive AKI shortly after pancreatitis onset, requiring kidney replacement therapy, but eventually showed good recovery. One patient treated with eculizumab had a faster recovery compared to others.
CLINICAL KIDNEY JOURNAL
(2021)
Article
Medicine, General & Internal
Sarah Dunn, Victoria Brocklebank, Andrew Bryant, Sonya Carnell, Thomas J. Chadwick, Sally Johnson, David Kavanagh, Jan Lecouturier, Michal Malina, Eoin Moloney, Yemi Oluboyede, Christopher Weetman, Edwin Kwan Soon Wong, Len Woodward, Neil Sheerin
Summary: This study aims to investigate the safety of stopping eculizumab treatment in patients with atypical haemolytic uraemic syndrome (aHUS) by monitoring disease activity and tracking thrombotic microangiopathy-related serious adverse events. It evaluates the effectiveness and feasibility of this treatment strategy.
Article
Transplantation
Shuichi Ito, Hiroshi Hataya, Akira Ashida, Riku Hamada, Tomoaki Ishikawa, Yumiko Ishikawa, Akihiko Shimono, Takao Konomoto, Tomoki Miyazawa, Masao Ogura, Kazuki Tanaka, Shoji Kagami
Summary: Eculizumab demonstrated good efficacy and tolerability in pediatric patients with aHUS in a real-world setting in Japan. The treatment led to significant improvements in platelet count, lactate dehydrogenase, and estimated glomerular filtration rate, and achieved complete TMA response, hematologic normalization, and sCr decrease in a high percentage of patients.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2023)
Article
Medicine, General & Internal
Min-Hua Tseng, Wen-Lang Fan, Hsuan Liu, Chia-Yu Yang, Jhao-Jhuang Ding, Hwei-Jen Lee, Shih-Ming Huang, Shih-Hua Lin, Jing-Long Huang
Summary: Renal thrombotic microangiopathy (TMA) in lupus nephritis (LN) patients is associated with complement overactivation and genetic mutations in complement regulatory proteins, leading to poor prognosis. Patients with renal TMA have higher serum urea levels, higher relapse rates, lower remission rates, and increased risks of end-stage renal disease and mortality. Reduced levels of serum complement factor H and plasma ADAMTS13 activity, along with mutations in genes responsible for complement regulation, may contribute to the development of renal TMA in LN patients.
FRONTIERS IN MEDICINE
(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
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)