ArticleArthritis and rheumatism2013
Somatic hypermutations confer rheumatoid factor activity in hepatitis C virus-associated mixed cryoglobulinemia.
Article in Arthritis and rheumatism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 48 citations in OpenAlex.
- The Role of Direct-Acting Antivirals (DAAs) in Hepatitis C Virus-Associated Lymphoproliferative Disorders.Cancers · 2026Review
- Autoantibodies in COVID-19: implications for disease severity and clinical outcomes.Frontiers in immunology · 2024Review
- Dual stimulation by autoantigen and CpG fosters the proliferation of exhausted rheumatoid factor-specific CD21Frontiers in immunology · 2023Article
- Rheumatoid Factor: A Novel Determiner in Cancer History.Cancers · 2021Article
- Structural Basis of a Conventional Recognition Mode of IGHV1-69 Rheumatoid Factors.Advances in experimental medicine and biology · 2021Review
- The Role of B Cells in Adult and Paediatric Liver Injury.Frontiers in immunology · 2021Review
- Salivary Gland Mucosa-Associated Lymphoid Tissue-Type Lymphoma From Sjögren's Syndrome Patients in the Majority Express Rheumatoid Factors Affinity-Selected for IgG.Arthritis & rheumatology (Hoboken, N.J.) · 2020Article
- A stereotyped light chain may shape virus-specific B-cell receptors in HCV-dependent lymphoproliferative disorders.Genes and immunity · 2020Article
- Treatment of chronic hepatitis C-associated cryoglobulinemia vasculitis at the era of direct-acting antivirals.Therapeutic advances in gastroenterology · 2020Review
- An MPER antibody neutralizes HIV-1 using germline features shared among donors.Nature communications · 2019Article
- Immunoglobulin gene analysis as a tool for investigating human immune responses.Immunological reviews · 2018Review
- Structure-function analyses of a stereotypic rheumatoid factor unravel the structural basis for germline-encoded antibody autoreactivity.The Journal of biological chemistry · 2018Article
- Structural Determination of the Broadly Reactive Anti-IGHV1-69 Anti-idiotypic Antibody G6 and Its Idiotope.Cell reports · 2017Article
- Persistence of exhaustion in cured hep C.Blood · 2017Article
- Innate and Adaptive Immune Responses in Chronic HCV Infection.Current drug targets · 2017Review
- Identification of a novel stereotypic IGHV4-59/IGHJ5-encoded B-cell receptor subset expressed by various B-cell lymphomas with high affinity rheumatoid factor activity.Haematologica · 2016Article
- Diagnostics and treatment of cryoglobulinaemia: it takes two to tango.Clinical reviews in allergy & immunology · 2014Review
- Immune control and failure in HCV infection--tipping the balance.Journal of leukocyte biology · 2014Review
- Regulation of B lymphocytes and plasma cells by innate immune mechanisms and stromal cells in rheumatoid arthritis.Expert review of clinical immunology · 2014Review
- Useful biomarkers for assessment of hepatitis C virus infection-associated autoimmune disorders.World journal of gastroenterology · 2014Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
objectiveHepatitis C virus (HCV) is the most frequent cause of mixed cryoglobulinemia (MC), which is characterized by endothelial deposition of rheumatoid factor (RF)-containing immune complexes and end-organ vasculitis. MC is a lymphoproliferative disorder in which B cells express RF-like Ig, yet its precise antigenic stimulus is unknown. We have proposed that IgG-HCV immune complexes stimulate B cell expansion and somatic hypermutation (SHM)-induced affinity maturation in part via engagement of an RF-like B cell receptor. This study was undertaken to test the hypothesis that SHM augments RF activity.
methodsRFs cloned from single B cells from 4 patients with HCV-associated MC (HCV-MC) were expressed as IgM, IgG, or IgG Fab. Selected Ig were reverted to germline. RF activity of somatically mutated Ig and germline-reverted Ig was determined by enzyme-linked immunosorbent assay.
resultsIg with SHM had RF activity, with the preference for binding being highest for IgG1, followed by IgG2 and IgG4, and lowest for IgG3, where there was no detectable binding. In contrast, reverted germline IgG exhibited markedly diminished RF activity. Competition with 1 μg/ml of protein A abrogated RF activity, suggesting specificity for IgG Fc. Swapping of mutated heavy-chain pairs and light-chain pairs also abrogated RF activity, suggesting that context-specific pairing of appropriate IgH and Igκ, in addition to SHM, is necessary for RF activity.
conclusionSHM significantly contributes to RF activity in HCV-MC patients, suggesting that autoreactivity in these patients arises through antigen-dependent SHM, as opposed to nondeletion of autoreactive germline Ig.
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