ArticleProceedings of the National Academy of Sciences of the United States of America2014
Translocalized IgA mediates neutralization and stimulates innate immunity inside infected cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- A systematic review and meta-analysis of the IgA seroprevalence in COVID-19 patients: Is there a role for IgA in COVID-19 diagnosis or severity?Microbiological research · 2022Pooled it
- Pulmonary Myeloid Cells in Mild Cases of COVID-19 Upregulate the Intracellular Fc ReceptorInternational journal of molecular sciences · 2025Article
- Profile of Humoral Immunity and B Cell Pool in Infection with the SARS-CoV-2 Prototype Strain and AZD1222 (ChAdOx nCoV-19) Vaccination.Vaccines · 2025Article
- TRIM21 regulation of IRF-mediated type I interferon signaling in systemic autoimmune diseases.Frontiers in immunology · 2025Review
- Role of IgA1 protease-producing bacteria in SARS-CoV-2 infection and transmission: a hypothesis.mBio · 2024Article
- TRIM21 and Fc-engineered antibodies: decoding its complex antibody binding mode with implications for viral neutralization.Frontiers in immunology · 2024Article
- Negative impact of immunoparesis in response to anti-SARS-CoV-2 mRNA vaccination of patients with multiple myeloma.International journal of hematology · 2024Article
- Roles of TRIM21/Ro52 in connective tissue disease-associated interstitial lung diseases.Frontiers in immunology · 2024Review
- Review
- Multiple Roles of TRIM21 in Virus Infection.International journal of molecular sciences · 2023Review
- Article
- Antibody Fc-chimerism and effector functions: When IgG takes advantage of IgA.Frontiers in immunology · 2023Review
- Drop the Needle; A Temperature Stable Oral Tablet Vaccine Is Protective against Respiratory Viral Pathogens.Vaccines · 2022Review
- B cell class switching in intestinal immunity in health and disease.Scandinavian journal of immunology · 2022Review
- Current Advances in Paper-Based Biosensor Technologies for Rapid COVID-19 Diagnosis.Biochip journal · 2022Review
- The emerging roles of TRIM21 in coordinating cancer metabolism, immunity and cancer treatment.Frontiers in immunology · 2022Review
- Point-of-care COVID-19 diagnostics powered by lateral flow assay.Trends in analytical chemistry : TRAC · 2021Review
- Rab11-FIP1 and Rab11-FIP5 Regulate pIgR/pIgA Transcytosis through TRIM21-Mediated Polyubiquitination.International journal of molecular sciences · 2021Article
- Serological assessment of SARS-CoV-2 infection during the first wave of the pandemic in Louisville Kentucky.Scientific reports · 2021Article
- Gastrointestinal mucosal immunity and COVID-19.World journal of gastroenterology · 2021Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
IgA is the most prevalent antibody type on mucosal surfaces and the second most prevalent antibody in circulation, yet its role in immune defense is not fully understood. Here we show that IgA is carried inside cells during virus infection, where it activates intracellular virus neutralization and innate immune signaling. Cytosolic IgA-virion complexes colocalize with the high-affinity antibody receptor tripartite motif-containing protein 21 (TRIM21) and are positive for lysine-48 ubiquitin chains. IgA neutralizes adenovirus infection in a TRIM21- and proteasome-dependent manner in both human and mouse cells. Translocated IgA also potently activates NF-κB signaling pathways in cells expressing TRIM21, whereas viral infection in the absence of antibody or TRIM21 is undetected. TRIM21 recognizes an epitope in IgG Fc that is not conserved in IgA; however, fluorescence anisotropy experiments demonstrate that direct binding to IgA is maintained. We use molecular modeling to show that TRIM21 forms a nonspecific hydrophobic seal around a β-loop structure that is present in IgG, IgM, and IgA, explaining how TRIM21 achieves such remarkable broad antibody specificity. The findings demonstrate that the antiviral protection afforded by IgA extends to the intracellular cytosolic environment.
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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.