ArticleJournal of translational medicine2019
Complement factors C3a and C5a mimick a proinflammatory microenvironment and increase HBV IGRA sensitivity.
Article in Journal of translational medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.
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Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it, 10 citations in OpenAlex.
- A bibliometric analysis of immunotherapy for chronic hepatitis B: trends and hotspots prediction.Frontiers in immunology · 2026Pooled it
- Pneumocystis Jirovecii Pneumonia: The Potential of KEX1, MSG1, and MSG2 as Key Antigens in Cytokine Release Assays.Diagnostics (Basel, Switzerland) · 2025Article
- Evaluation of three novel antigens and costimulatory agents for improvement of M. Tuberculosis specific interferon gamma release assays.BMC infectious diseases · 2025Article
- Identification of Adipsin as a Biomarker of Beta Cell Function in Patients with Type 2 Diabetes.Journal of clinical medicine · 2024Article
- The complement C3a-C3aR and C5a-C5aR pathways promote viability and inflammation of human retinal pigment epithelium cells by targeting NF-κB signaling.Experimental and therapeutic medicine · 2022Article
- The role of complement in the clinical course of hepatocellular carcinoma.Immunity, inflammation and disease · 2022Article
- New Insights into the Role of the Complement System in Human Viral Diseases.Biomolecules · 2022Review
- Hepatitis B Virus Infection Among Leprosy Patients: A Case for Polymorphisms Compromising Activation of the Lectin Pathway and Complement Receptors.Frontiers in immunology · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundHepatitis B virus (HBV) infections represent a global health problem and chronic hepatitis B (CHB) leads to liver cirrhosis and hepatocellular carcinoma. Thus, timely diagnosis of hepatitis B is crucial to ensure adequate treatment. We developed a powerful and rapid whole blood-based cytokine release assay assessing cellular immune responses to HBV antigens. IL-2 and IFNγ release in this assay depicts hepatitis B vaccination status. Of note, CHB goes along with elevated C5a concentrations in plasma. We aim at mimicking the proinflammatory microenvironment associated with HBV infection to enhance the diagnostic quality of our HBV specific cytokine release assay. We specifically investigated the potential of the complement factors C3a and C5a as costimulators and analyzed their potential effects on activation marker expression on T cells and antigen presenting cells.
resultsWhole blood from 87 healthy individuals (n = 59 hepatitis B vaccinated, n = 28 unvaccinated) was stimulated with HBV surface antigen (HBsAg) in presence or absence of C3a or C5a, respectively. Further, C3a and C5a were used in combination to investigate potential synergistic effects. IL-2 and IFNγ levels in plasma were quantified using ELISA. Complement factor C5a specifically enhances HBsAg-mediated IL-2 (690.3 ± 195.4 pg/ml vs. 789.4 ± 216.5 pg/ml) and IFNγ (146.0 ± 43.1 pg/ml vs. 336.7 ± 67.9 pg/ml) responses in whole blood. Similar cytokine levels were measured when both C3a and C5a were used. With a diagnostic specificity of 90% the IFNγ release assay reached a diagnostic sensitivity of 49.2% upon whole blood stimulation with HBsAg alone, but of 78.9% when HBsAg was combined with C3a and C5a.
conclusionsInnate signals mediated via complement pathways contribute to HBV-specific cellular immune responses. The massively improved diagnostic sensitivity of the IFNγ release assay after addition of C3a and C5a demonstrates that these effects render whole blood-based cytokine release assays even more potent as screening tools in HBV immunology and HBV vaccination studies.
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