ArticleProceedings of the National Academy of Sciences of the United States of America2009
Tumor-associated and microbial proteases compromise host IgG effector functions by a single cleavage proximal to the hinge.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 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.
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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.
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Who cites it
49 citing papers in PubMed, 97 citations in OpenAlex.
- Trial
- 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
- Impact of cellular proteases on the function of antiviral antibodies.Journal of virology · 2026Review
- 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
- Novel assays to assess the prevalence and neutralizing potential of anti-IdeS antibodies in healthy humans.Frontiers in immunology · 2026Article
- Proteases in intestinal health and disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- 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
- Optimizing Anti-PD1 Immunotherapy: An Overview of Pharmacokinetics, Biomarkers, and Therapeutic Drug Monitoring.Cancers · 2025Review
- Neutralizing Antibodies vs. Viruses: Interacting Mechanisms and Escape Tactics.Microorganisms · 2025Review
- Outsmarting Pathogens with Antibody Engineering.Annual review of chemical and biomolecular engineering · 2023Review
- Article
- Extensive substrate recognition by the streptococcal antibody-degrading enzymes IdeS and EndoS.Nature communications · 2022Article
- Impairment of IgG Fc functions promotes tumor progression and suppresses NK cell antitumor actions.Communications biology · 2022Article
- Imlifidase for the treatment of anti-HLA antibody-mediated processes in kidney transplantation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2022Review
- An Introduction to Bacterial Biofilms and Their Proteases, and Their Roles in Host Infection and Immune Evasion.Biomolecules · 2022Review
- Transient proteolysis reduction ofFrontiers in plant science · 2022Article
- Article
- Antibody-Dependent Enhancement of Bacterial Disease: Prevalence, Mechanisms, and Treatment.Infection and immunity · 2021Review
- A structure-based engineering approach to abrogate pre-existing antibody binding to biotherapeutics.PloS one · 2021Article
- Structural features of bovine colostral immunoglobulin that confer proteolytic stability in a simulated intestinal fluid.The Journal of biological chemistry · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The successful elimination of pathogenic cells and microorganisms by the humoral immune system relies on effective interactions between host immunoglobulins and Fc gamma receptors on effector cells, in addition to the complement system. Essential Ig motifs that direct those interactions reside within the conserved IgG lower hinge/CH2 interface. We noted that a group of tumor-related and microbial proteases cleaved human IgG1s in that region, and the "nick" of just one of the heavy chains profoundly inhibited IgG1 effector functions. We focused on IgG1 monoclonal antibodies (mAbs) since IgG1 is the most abundant human subclass and demonstrates robust Fc-mediated effector functions. The loss of Fc-mediated cell killing activities was correlated with diminished binding to the Fc gamma family of receptors, but a similar decrease in affinity was not observed toward the FcRn receptor that maintains IgG in circulation. Endogenous human IgG cleavage products of comparable size to mAbs with the single cleavage were detected by Western blot analysis in synovial fluid from patients with rheumatoid arthritis and in breast carcinoma extracts. Their detection is problematic under physiological conditions, since there is no loss of structure, and antigen-binding capability is unaffected. These findings suggest that within the hostile proteolytic microenvironments associated with many diseases, key effector functions of host IgGs, or therapeutic Abs, may be compromised.
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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.