Over recent years, great attention has been paid to the role of the complement system in the pathogenesis of age-related macular degeneration (AMD). In particular, several studies have highlighted a link between AMD development and complement dysregulation, which can probably be explained as a complement cascade hyperactivation resulting from the presence of a series of risk factors such as aging; smoking; obesity; alcohol consumption; exposure to pesticides, industrial chemicals, or pollution; and other causes of oxidative stress. This hypothesis has been mainly supported by the presence of complement mediators as constituents of drusen, representing one of the earliest and most characteristic signs of retinal damage in AMD. Additionally, activated complement mediators and some complement regulators, such as vitronectin, have been found not only in the drusen and adjacent retinal areas but also in the peripheral blood of patients with AMD. Therefore, we aim to provide a review of recently studied complement factors to highlight their role in the pathogenesis of AMD and to evaluate new potential therapeutic strategies.
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http://dx.doi.org/10.1007/s40266-021-00914-x | DOI Listing |
Pharmaceutics
January 2025
Department of General and Transplant Surgery, Poznan University of Medical Sciences, 60-355 Poznan, Poland.
: Chronic antibody-mediated rejection (cAMR) constitutes a serious challenge in the long-term success of organ transplantation. It is associated with donor-specific antibodies (DSAs) which activate a complement pathway in response to the presence of human leukocyte antigens (HLAs) on the graft, which results in chronic inflammation and leads to graft dysfunction. One of the recent promising methods of cAMR treatment is a recombinant humanized anti-interleukin-6 receptor (IL-6R) monoclonal antibody referred to as Tocilizumab (TCZ).
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Immunology Department, University Hospital Marqués de Valdecilla, 39008 Santander, Spain.
The human leukocyte antigen (HLA) system plays a critical role in transplant immunology, influencing outcomes through various immune-mediated rejection mechanisms. Hyperacute rejection is driven by preformed donor-specific antibodies (DSAs) targeting HLAs, leading to complement activation and graft loss within hours to days. Acute rejection typically occurs within six months post-transplantation, involving cellular and humoral responses, including the formation of de novo DSAs.
View Article and Find Full Text PDFClin Pharmacol Ther
January 2025
Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.
Iptacopan, a first-in-class complement factor B inhibitor acting proximally in the alternative complement pathway, has been shown to be safe and effective for patients with complement-mediated diseases. Iptacopan selectively binds with high affinity to factor B, a soluble, plasma-based, hepatically produced protein. Factor B is abundant in the circulation but can be saturated at the iptacopan clinical dose of 200 mg twice daily.
View Article and Find Full Text PDFEur J Immunol
January 2025
Molecular Horizons and School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, Australia.
P2X7 is an extracellular adenosine 5'-triphosphate (ATP)-gated cation channel that plays various roles in inflammation and immunity. P2X7 is present on peripheral blood monocytes, dendritic cells (DCs), and innate and adaptive lymphocytes. The anti-human P2X7 monoclonal antibody (mAb; clone L4), used for immunolabelling P2X7 or blocking P2X7 activity, is a murine IgG2 antibody, but its ability to mediate complement-dependent cytotoxicity (CDC) is unknown.
View Article and Find Full Text PDFCurr Issues Mol Biol
January 2025
Children & Adolescent Hematology-Oncology Unit, Second Department of Pediatrics, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
Immune thrombocytopenia (ITP) in pediatric patients is a common cause of isolated thrombocytopenia. Various pathophysiological mechanisms are implicated in ITP pathogenesis, including the production of autoantibodies against components of platelets (PLTs) by B-cells, the activation of the complement system, phagocytosis by macrophages mediated by Fcγ receptors, the dysregulation of T cells, and reduced bone marrow megakaryopoiesis. ITP is commonly manifested with skin and mucosal bleeding, and it is a diagnosis of exclusion.
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