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)
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)
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
Ophthalmology
Anita Grover, Sethu Sankaranarayanan, Vidhu Mathur, Poojan Suri, Haiyan Qiu, Yaisa Andrews-Zwilling, Kirsten Mease, Lori K. Taylor, Ellen Cahir-McFarland, Sanjay Keswani, Ted Yednock
Summary: ANX007 is an antibody that blocks the binding of C1q and inhibits the classical complement cascade. It has potential therapeutic effects for neurodegenerative ophthalmic diseases. Experimental studies showed that ANX007 can target and engage with C1q in the retina, supporting its further clinical evaluation.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2023)
Review
Pharmacology & Pharmacy
Michael J. Tolentino, Andrew J. Tolentino
Summary: This paper reviews the pathogenesis of macular degeneration, current and failed therapeutics, therapies undergoing clinical trials and provides a rationale for why certain AMD therapies may succeed or fail.
EXPERT OPINION ON INVESTIGATIONAL DRUGS
(2022)
Review
Pharmacology & Pharmacy
Lorenzo Ferro Desideri, Dmitri Artemiev, Enrico Bernardi, Karin Paschon, Souska Zandi, Martin Zinkernagel, Rodrigo Anguita
Summary: Geographic atrophy (GA), a progressive form of age-related macular degeneration (AMD), leads to severe visual impairment and central vision loss. Targeting the complement system has emerged as a promising strategy for the treatment of GA.
EXPERT OPINION ON INVESTIGATIONAL DRUGS
(2023)
Review
Immunology
Laura Lucientes-Continente, Barbara Marquez-Tirado, Elena Goicoechea de Jorge
Summary: The factor H protein family is a network of proteins that control the fate of the complement alternative pathway and play a role in various diseases. Different members of the FH family have different functions in regulating the complement pathway. Recent research has shed light on their biological roles and pathogenicity.
IMMUNOLOGICAL REVIEWS
(2023)
Article
Ophthalmology
Huixun Jia, Tong LI, Junran Sun, Yuanyuan Gong, Haiyun Liu, Hong Wang, Jieqiong Chen, Wenjia Liu, Shujie Lu, Liqi Feng, Qiuchen Wan, Lei Qian, Fenghua Wang, Xiaoling Liu, Xiaodong Sun
Summary: This study aimed to evaluate the safety, tolerability, and efficacy of efdamrofusp alfa in patients with neovascular age-related macular degeneration (nAMD). The study design was prospective randomized, open-label, multiple ascending-dose, phase 1b. The results showed that intravitreal efdamrofusp alfa dosed up to 4 mg every 4 weeks was well tolerated in nAMD patients with similar vision acuity and anatomic improvements.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2023)
Article
Immunology
Yen-Ling Chiu, Wei-Chou Lin, Kai-Hsiang Shu, Yi-Wen Fang, Fan-Chi Chang, Yu-Hsiang Chou, Ching-Fang Wu, Wen-Chih Chiang, Shuei-Liong Lin, Yung-Ming Chen, Ming-Shiou Wu
Summary: The study found that IgAN patients had higher levels of C5a, factor Ba, and Gd-IgA(1) in plasma compared to healthy controls, with Gd-IgA(1) positively correlated with C5a and factor Ba. Factor Ba and Gd-IgA(1) levels were positively associated with proteinuria, and negatively associated with renal function. Immunosuppressive therapy significantly reduced plasma levels of C5a, factor Ba, and Gd-IgA(1) in patients, leading to decreased proteinuria and stable renal function.
FRONTIERS IN IMMUNOLOGY
(2021)
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
Pallavi Manral, Tiffany N. Caza, Aaron J. Storey, Laurence H. Beck, Dorin-Bogdan Borza
Summary: This study analyzed the serum of patients with THSD7A-associated membranous nephropathy and found that predominantly IgG4 anti-THSD7A antibodies can activate the complement system, but at high IgG4 density and through the alternative pathway.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Hematology
Ayiesha P. Barnes, Sanjay Khandelwal, Simone Sartoretto, Sooho Myoung, Samuel J. Francis, Grace M. Lee, Lubica Rauova, Douglas B. Cines, Jon T. Skare, Charles E. Booth, Brandon L. Garcia, Gowthami M. Arepally
Summary: The alternative pathway plays a minor role in complement activation by HIT immune complexes, while the classical pathway dominates in this process.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
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
Cell Biology
Xinxuan Cheng, Danxue He, Chunyan Liao, Sijie Lin, Liying Tang, Yuan-Liang Wang, Jiaoyue Hu, Wei Li, Zuguo Liu, Yalin Wu, Yi Liao
Summary: The accumulation of all-trans-retinal (atRAL) has been proposed as a pathogenic factor in Stargardt disease type 1 (STGD1) and age-related macular degeneration (AMD). The study showed that atRAL induced complement activation through the alternative pathway in retinal pigment epithelium (RPE) cells, and led to the production of interleukin-1 beta. Inhibition of p38 and c-Jun N-terminal kinase (JNK) signaling pathways ameliorated complement activation in RPE cells, suggesting a potential therapeutic target for macular degeneration.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)