ReviewFrontiers in immunology2016
Alternative Pathway Dysregulation and the Conundrum of Complement Activation by IgG4 Immune Complexes in Membranous Nephropathy.
Review in Frontiers in immunology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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
32 citing papers in PubMed, 52 citations in OpenAlex.
- Distinct Complement Activation Profiles Between NELL1- and PLA2R-Associated Membranous Nephropathy: A Clinicopathological and Proteomic Study.Nephrology (Carlton, Vic.) · 2026Article
- Early kinetics of anti-PLA2R-IgG4 predicts rituximab response in membranous nephropathy: a prospective biomarker study.Scientific reports · 2026Article
- Perlecan is a novel target of autoantibodies in anti-glomerular basement membrane disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Article
- Case report: Coexistence of optic neuritis and primary anti-PLA2R-positive membranous nephropathy.BMC neurology · 2025Article
- The role of B lymphocyte subsets in nephrotic syndrome: functions, mechanisms, clinical significance and future perspectives.Frontiers in immunology · 2025Review
- Factor H-related 1 and heparan sulfate architecture contribute to complement dysregulation in C3 glomerulopathy.Frontiers in immunology · 2025Article
- Clinicopathological characteristics and outcomes of PLA2R related idiopathic membranous nephropathy in patients with seronegative PLA2R antibodies.Renal failure · 2024Article
- Current progress in CAR-based therapy for kidney disease.Frontiers in immunology · 2024Review
- Kidney diseases.Immunological reviews · 2023Review
- The Role of Anti-PLAInternational journal of environmental research and public health · 2022Review
- Clinical Evaluation of Antiphospholipase A2 Receptor IgG4 level and Its IgG4-to-IgG Ratio Based on Quantitative Immunoassays in Idiopathic Membranous Nephropathy.BioMed research international · 2022Article
- Hypercholesterolemia Correlates With Glomerular Phospholipase A2 Receptor Deposit and Serum Anti-Phospholipase A2 Receptor Antibody and Predicts Proteinuria Outcome in Idiopathic Membranous Nephropathy.Frontiers in immunology · 2022Article
- Identification of Hub Genes and Immune-Related Pathways for Membranous Nephropathy by Bioinformatics Analysis.Frontiers in physiology · 2022Article
- The Alternative Pathway Is Necessary and Sufficient for Complement Activation by Anti-THSD7A Autoantibodies, Which Are Predominantly IgG4 in Membranous Nephropathy.Frontiers in immunology · 2022Article
- Membranous nephropathy: Systems biology-based novel mechanism and traditional Chinese medicine therapy.Frontiers in pharmacology · 2022Review
- Inhibition of the Wnt/β-catenin signaling pathway reduces autophagy levels in complement treated podocytes.Experimental and therapeutic medicine · 2021Article
- Clinical significance of glomerular C3 deposition in primary membranous nephropathy.Journal of nephrology · 2021Article
- Altered glycosylation of IgG4 promotes lectin complement pathway activation in anti-PLA2R1-associated membranous nephropathy.The Journal of clinical investigation · 2021Article
- Membranous nephropathy: diagnosis, treatment, and monitoring in the post-PLA2R era.Pediatric nephrology (Berlin, Germany) · 2021Review
- How Times Have Changed! A Cornucopia of Antigens for Membranous Nephropathy.Frontiers in immunology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author at 1 institution in 1 country.
Funding
Abstract
Membranous nephropathy (MN), a major cause of nephrotic syndrome, is a non-inflammatory immune kidney disease mediated by IgG antibodies that form glomerular subepithelial immune complexes. In primary MN, autoantibodies target proteins expressed on the podocyte surface, often phospholipase A2 receptor (PLA2R1). Pathology is driven by complement activation, leading to podocyte injury and proteinuria. This article overviews the mechanisms of complement activation and regulation in MN, addressing the paradox that anti-PLA2R1 and other antibodies causing primary MN are predominantly (but not exclusively) IgG4, an IgG subclass that does not fix complement. Besides immune complexes, alterations of the glomerular basement membrane (GBM) in MN may lead to impaired regulation of the alternative pathway (AP). The AP amplifies complement activation on surfaces insufficiently protected by complement regulatory proteins. Whereas podocytes are protected by cell-bound regulators, the GBM must recruit plasma factor H, which inhibits the AP on host surfaces carrying certain polyanions, such as heparan sulfate (HS) chains. Because HS chains present in the normal GBM are lost in MN, we posit that the local complement regulation by factor H may be impaired as a result. Thus, the loss of GBM HS in MN creates a micro-environment that promotes local amplification of complement activation, which in turn may be initiated via the classical or lectin pathways by subsets of IgG in immune complexes. A detailed understanding of the mechanisms of complement activation and dysregulation in MN is important for designing more effective therapies.
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.