Mesangial deposition of aberrantly glycosylated IgA1 (agIgA1) and its immune complexes is a key pathogenic mechanism of IgA nephropathy (IgAN). However, treatment of IgAN remains ineffective. We report here that bacteria-derived IgA proteases are capable of degrading these pathogenic agIgA1 and derived immune complexes in vitro and in vivo. By screening 14 different bacterial strains (6 species), we found that 4 bacterial IgA proteases from H. influenzae, N. gonorrhoeae and N. meningitidis exhibited high cleaving activities on serum agIgA1 and artificial galactose-depleted IgA1 in vitro and the deposited agIgA1-containing immune complexes in the mesangium of renal biopsy from IgAN patients and in a passive mouse model of IgAN in vitro. In the modified mouse model of passive IgAN with abundant in situ mesangial deposition of the agIgA-IgG immune complexes, a single intravenous delivery of IgA protease from H. influenzae was able to effectively degrade the deposited agIgA-IgG immune complexes within the glomerulus, demonstrating a therapeutic potential for IgAN. In conclusion, the bacteria-derived IgA proteases are biologically active enzymes capable of cleaving the circulating agIgA and the deposited agIgA-IgG immune complexes within the kidney of IgAN. Thus, the use of such IgA proteases may represent a novel therapy for IgAN.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971536 | PMC |
| http://dx.doi.org/10.1038/srep30964 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Anti-platelet factor 4 antibody-mediated disorders: an updated narrative review.
Semin Thromb Hemost
January 2025
of Medicine, Universita degli Studi di Padova Scuola di Medicina e Chirurgia, Padova, Italy.
Anti-platelet factor 4 (PF4) antibody-mediated disorders are a heterogenous group of diseases characterized by the presence of highly pathogenic immunoglobulins G directed against PF4 and/or PF4/heparin complexes. These antibodies are able to activate platelets, neutrophils and monocytes, thus resulting in thrombocytopenia and a hypercoagulable state. Five different forms of anti-PF4 antibody-mediated disorders have been identified: i) classic heparin-induced thrombocytopenia (cHIT) mediated by heparin and certain polyanionic drugs; ii) autoimmune HIT (aHIT) characterized by the presence of anti-PFA/polyanion antibodies that can strongly activate platelets even in the absence of heparin; iii) spontaneous HIT (spHIT) characterized by thrombocytopenia and thrombosis without proximate exposure to heparin, with two subtypes: (a) post-total knee arthroplasty, and cardiac surgery using cardiopulmonary bypass or extracorporeal membrane oxygenation, and (b) post-infections; iv) vaccine-induced immune thrombotic thrombocytopenia (VITT) characterized by thrombocytopenia, arterial and venous thrombosis, or secondary hemorrhage after receiving adenoviral vector vaccines for COVID-19; v) VITT-like disorders triggered by adenoviral infections.
View Article and Find Full Text PDFanalysis of the effect of HCV genotype-specific polymorphisms in Core, NS3, NS5A, and NS5B proteins on T-cell epitope processing and presentation.
Front Microbiol
January 2025
Department of Biomedical Sciences, Nazarbayev University School of Medicine, Astana, Kazakhstan.
Background: HCV genotypes are 30-35% polymorphic at the nucleotide level, while subtypes within the same genotype differ by nearly 20%. Although previous studies have shown the immune escape potential of several mutations within the HCV proteins, little is known about the effect of genotype/subtype-specific gene polymorphism on T-cell immunity. Therefore, this study employed several methods to examine the impact of genotype/subtype-specific polymorphisms in Core, NS3, NS5A, and NS5B sequences on T cell epitope processing and HLA-epitope interactions.
View Article and Find Full Text PDFMolecular basis of vitamin K driven γ-carboxylation at membrane interface.
Nature
January 2025
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA.
The γ-carboxylation of glutamate residues enables Ca-mediated membrane assembly of protein complexes that support broad physiological functions including hemostasis, calcium homeostasis, immune response, and endocrine regulation. Modulating γ-carboxylation level provides prevalent treatments for hemorrhagic and thromboembolic diseases. This unique posttranslational modification requires vitamin K hydroquinone (KH) to drive highly demanding reactions catalyzed by the membrane-integrated γ-carboxylase (VKGC).
View Article and Find Full Text PDFInnate Immunity Never "NODs" Off: NLRs Regulate the Host Anti-Viral Immune Response.
Immunol Rev
March 2025
Graduate Program in Translational Biology, Medicine, and Health, Virginia Tech, Roanoke, Virginia, USA.
A robust innate immune response is essential in combating viral pathogens. However, it is equally critical to quell overzealous immune signaling to limit collateral damage and enable inflammation resolution. Pattern recognition receptors are critical regulators of these processes.
View Article and Find Full Text PDFObjective: Aim: To investigate the effect of succinic acid on the humoral component of the immune system in rats.
Patients And Methods: Materials and Methods: The study was conducted on two groups of mature non-linear white rats (males) of similar weight (200-270 g, aged 6-8 months), with 5 animals in each group. The control group was fed a standard diet with free access to water throughout the experiment.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!