ArticleClinical and experimental immunology2004
The quantitative role of alternative pathway amplification in classical pathway induced terminal complement activation.
Article in Clinical and experimental immunology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 177 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
177 citing papers in PubMed, 1 synthesis or guideline pooled it, 306 citations in OpenAlex.
- Therapeutic Targeting of the Complement System: From Rare Diseases to Pandemics.Pharmacological reviews · 2021Pooled it
- Iptacopan for Immune Thrombocytopenia and Cold Agglutinin Disease: A Global Phase 2 Basket Clinical Trial.American journal of hematology · 2026Trial
- Trial
- Acute heart failure following myocardial infarction: complement activation correlates with the severity of heart failure in patients developing cardiogenic shock.ESC heart failure · 2018Trial
- Advances in Complement Research: from Pathophysiology to Precision Medicine.Physiology (Bethesda, Md.) · 2026Review
- Type 2 and type 1 diabetes have opposing effects on the systemic murine complement alternative pathway.iScience · 2026Article
- Inhibition of Classical and Alternative Complement Pathway by Ravulizumab and Eculizumab.Annals of clinical and translational neurology · 2026Article
- The C-terminal domain of Staphylococcus aureus Efb recruits FHR-2 to C3b, synergistically inhibiting the terminal complement pathway.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Breaking tolerance in the glomerulus: complement as a driver and therapeutic target in IgA nephropathy.Frontiers in medicine · 2026Review
- Point-of-care assessment of complement activation in the ICU: a feasibility study of rapid terminal complement complex detection in critical illness.Frontiers in immunology · 2026Article
- Properdin deficiency or anti-properdin treatment ameliorates disease in the C3 gain-of-function mouse model of atypical haemolytic uraemic syndrome.Frontiers in immunology · 2026Article
- Research Progress in Pharmacological Targeted Therapy for Myasthenia Gravis.Journal of inflammation research · 2026Review
- MUC4 mutations promote a thrombotic phenotype in patients with paroxysmal nocturnal haemoglobinuria by increasing the deposition of terminal complement.Clinical and translational medicine · 2026Article
- CFDFrontiers in immunology · 2026Article
- Association between systemic complement levels and choroidal thickness in advanced non-neovascular age-related macular degeneration.Scientific reports · 2025Article
- Complement factor D (adipsin) mediates pressure-pain hypersensitivity post destabilization of medial meniscus injury.Arthritis research & therapy · 2025Article
- Intercepting the complement amplification loop through podocyte MC5R signaling ameliorates membranous nephropathy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- The role of complement in long COVID pathogenesis.JCI insight · 2025Review
- New and Emerging Biological Therapies for Myasthenia Gravis: A Focussed Review for Clinical Decision-Making.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- Characterization of the colostrum proteome of primiparous Holstein cows and its association with colostrum immunoglobulin G concentrations.Journal of animal science and biotechnology · 2025Article
117 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Complement activation with formation of biologically potent mediators like C5a and the terminal C5b-9 complex (TCC) contributes essentially to development of inflammation and tissue damage in a number of autoimmune and inflammatory conditions. A particular role for complement in the ischaemia/reperfusion injury of the heart, skeletal muscle, central nervous system, intestine and kidney has been suggested from animal studies. Previous experiments in C3 and C4 knockout mice suggested an important role of the classical or lectin pathway in initiation of complement activation during intestinal ischaemia/reperfusion injury while later use of factor D knockout mice showed the alternative pathway to be critically involved. We hypothesized that alternative pathway amplification might play a more critical role in classical pathway-induced C5 activation than previously recognized and used pathway-selective inhibitory mAbs to further elucidate the role of the alternative pathway. Here we demonstrate that selective blockade of the alternative pathway by neutralizing factor D in human serum diluted 1 : 2 with mAb 166-32 inhibited more than 80% of C5a and TCC formation induced by solid phase IgM and solid- and fluid-phase human aggregated IgG via the classical pathway. The findings emphasize the influence of alternative pathway amplification on the effect of initial classical pathway activation and the therapeutic potential of inhibiting the alternative pathway in clinical conditions with excessive and uncontrolled complement activation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.