ArticleClinical & translational immunology2023
The contribution of the alternative pathway in complement activation on cell surfaces depends on the strength of classical pathway initiation.
Article in Clinical & translational immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Reducing sialylation in melanoma increases classical pathway-mediated complement activation.iScience · 2026Article
- Advances in Complement Research: from Pathophysiology to Precision Medicine.Physiology (Bethesda, Md.) · 2026Review
- The Complosome: An Emerging Intracellular Complement Network in Cancer Development and Therapy.International journal of molecular sciences · 2026Review
- Innate immune response to AAV-based gene therapy vectors: Mechanisms of complement activation and cytokine release.Molecular therapy. Methods & clinical development · 2025Article
- The immune system in cardiovascular diseases: from basic mechanisms to therapeutic implications.Signal transduction and targeted therapy · 2025Review
- Complement Factor B Deficiency Is Dispensable for Female Fertility but Affects Microbiome Diversity and Complement Activity.International journal of molecular sciences · 2025Article
- Factor B as a therapeutic target for the treatment of complement-mediated diseases.Frontiers in immunology · 2025Review
- The role of complement in the immunopathogenesis of acetylcholine receptor antibody-positive generalized myasthenia gravis: bystander or key player?Frontiers in immunology · 2025Review
- Article
- Complement Activation in Nephrotic Glomerular Diseases.Biomedicines · 2024Review
- Inhibition of the C1s Protease and the Classical Complement Pathway by 6-(4-Phenylpiperazin-1-yl)Pyridine-3-Carboximidamide and Chemical Analogs.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Natural Modulators of Key Signaling Pathways in Skin Inflammageing.Clinical, cosmetic and investigational dermatology · 2024Review
- Heme Interactions as Regulators of the Alternative Pathway Complement Responses and Implications for Heme-Associated Pathologies.Current issues in molecular biology · 2023Review
- Factors affecting IgG4-mediated complement activation.Frontiers in immunology · 2023Article
- Unleashing the power of complement activation: unraveling renal damage in human anti-glomerular basement membrane disease.Frontiers in immunology · 2023Review
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Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Objectives: The complement system is an important component of innate immunity. The alternative pathway (AP) amplification loop is considered an essential feed forward mechanism for complement activation. However, the role of the AP in classical pathway (CP) activation has only been studied in ELISA settings. Here, we investigated its contribution on physiologically relevant surfaces of human cells and bacterial pathogens and in antibody-mediated complement activation, including in autoimmune haemolytic anaemia (AIHA) setting with autoantibodies against red blood cells (RBCs). Methods: We evaluated the contribution of the AP to complement responses initiated through the CP on human RBCs by serum of AIHA patients and recombinant antibodies. Moreover, we studied complement activation on Results: We show that the amplification loop is redundant when efficient CP activation takes place. This is independent of the presence of membrane-bound complement regulators. The role of the AP may become significant when insufficient CP complement activation occurs, but this depends on antibody levels and (sub)class. Our data indicate that therapeutic intervention in the amplification loop will most likely not be effective to treat antibody-mediated diseases. Conclusion: The AP can be bypassed through efficient CP activation. The AP amplification loop has a role in complement activation during conditions of modest activation via the CP, when it can allow for efficient complement-mediated killing.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.