ReviewmAbs
Cleavage of IgGs by proteases associated with invasive diseases: an evasion tactic against host immunity?
Review in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
What it found
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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
79 citing papers in PubMed, 146 citations in OpenAlex.
- Tisagenlecleucel immunogenicity in relapsed/refractory acute lymphoblastic leukemia and diffuse large B-cell lymphoma.Blood advances · 2021Trial
- Higher mucosal antibody concentrations in women with genital tract inflammation.Scientific reports · 2021Trial
- Trial
- Specificity of human anti-variable heavy (VH ) chain autoantibodies and impact on the design and clinical testing of a VH domain antibody antagonist of tumour necrosis factor-α receptor 1.Clinical and experimental immunology · 2015Trial
- Autoantibodies to variable heavy (VH) chain Ig sequences in humans impact the safety and clinical pharmacology of a VH domain antibody antagonist of TNF-α receptor 1.Journal of clinical immunology · 2013Trial
- The expanding role of protease therapeutics (2012-2026): from replacement therapies to immune system modulation and beyond.The Biochemical journal · 2026Review
- Identification and Characterization of Novel Human IgG-Degrading Enzymes.Biochemistry · 2026Article
- Translational insights into manufacturability and stability of broadly neutralizing antibodies for pediatric HIV prevention: lessons from plant-produced CAP256-VRC26.25.Frontiers in pediatrics · 2026Article
- Therapeutic IgG- and IgM-specific proteases disarm the acetylcholine receptor autoantibodies that drive myasthenia gravis pathology.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Porous Silicon Nanoparticle Hydrogel Formulation for Topical Delivery of Flightless I Neutralizing Antibody and Improved Diabetic Wound Healing.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
- Structural and functional characterization of IdeC, a novel IgG-specific protease ofInfection and immunity · 2025Article
- Tumor Proteolytic Activity in Esophageal Cancer.Bulletin of experimental biology and medicine · 2025Article
- Current status and future prospects of cancer-derived immunoglobulins in pancreatic cancer.Journal of Cancer · 2025Review
- Enhancing the Therapeutic Potential of Peptide Antibiotics Using Bacteriophage Mimicry Strategies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Research Progress on Immune Evasion ofMicroorganisms · 2024Review
- Circulating IgG Fragments for Gastric Cancer and Esophageal Cancer.Diagnostics (Basel, Switzerland) · 2024Article
- Guiding antibiotics towards their target using bacteriophage proteins.Nature communications · 2024Article
- Direct Comparison of the Hinge-Cleaving Proteases IgdE and BdpK for LC-MS-Based IgG1 Clonal Profiling.Analytical chemistry · 2024Article
- Critical Analysis of Thrombocytopenia Associated With Glycoprotein IIb/IIIa Inhibitors and Potential Role of Zalunfiban, a Novel Small Molecule Glycoprotein Inhibitor, in Understanding the Mechanism(s).Journal of the American Heart Association · 2023Review
- Prediction of anti-TNF therapy failure in ulcerative colitis patients by ensemble machine learning: A prospective study.Heliyon · 2023Article
19 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
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The effective functioning of immunoglobulins and IgG mAbs in removing pathological cells requires that the antigen binding regions and the Fc (effector) domain act in concert. The hinge region that connects these domains itself presents motifs that engage Fc receptors on immune effector cells to achieve cell lysis. In addition, sequences in the lower hinge/CH2 and further down the CH2 region are involved in C1q binding and complement-mediated cell killing. Proteolytic enzymes of little relevance to human physiology were successfully used for decades to generate fragments of IgGs for reagent and therapeutic use. It was subsequently noted that tumor-related and microbial proteases also cleaved human IgG specifically in the hinge region. We have shown previously that the "nick" of just one of the lower hinge heavy chains of IgG unexpectedly prevented many effector functions without impacting antigen binding. Of interest, related single-cleaved IgG breakdown products were detected in breast carcinoma extracts. This suggested a pathway by which tumors might avoid host immune surveillance under a cloak of proteolytically-generated, dysfunctional antibodies that block competent IgG binding. The host immune system cannot be blind to this pathway since there exists a widespread, low-titer incidence of anti-hinge (cleavage-site) antibodies in the healthy population. The prevalence of anti-hinge reactivity may reflect an ongoing immune recognition of normal IgG catabolism. Tumor growth and bacterial infections potentially generate hostile proteolytic environments that may pose harsh challenges to host immunity. Recent findings involving physiologically-relevant proteases suggest that the potential loss of key effector functions of host IgGs may result from subtle and limited proteolytic cleavage of IgGs and that such events may facilitate the incursion of invasive cells in local proteolytic settings.
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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.