ArticleArthritis research & therapy2021
Evolution of anti-modified protein antibody responses can be driven by consecutive exposure to different post-translational modifications.
Article in Arthritis research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
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- Complement Activation by Post-Translationally Modified Proteins: Links to Chronic Inflammation and Autoimmunity.Immunological reviews · 2026Review
- Anti-Modified Protein Antibodies in Rheumatoid Arthritis: Pathogenic, Protective, or Passive Bystander?Immunological reviews · 2026Review
- Beyond Sequence: Posttranslational Remodeling of Antigens in Autoimmunity.Immunological reviews · 2026Review
- Synovial microenvironment and fluorescence imaging for early rheumatoid arthritis diagnosis.Journal of pharmaceutical analysis · 2026Review
- Cross-Reactivity of Antiphospholipid Antibodies with Gut Commensal Proteins in Antiphospholipid Syndrome.TH open : companion journal to thrombosis and haemostasis · 2026Article
- Regulators and Conductors of Immunity: Natural Immune System in Health and Autoimmunity.International journal of molecular sciences · 2025Review
- Anti-Modified Peptide Antibodies (AMPAs) in Rheumatoid Arthritis: Study of the Diagnostic Value of Citrullinated, Homocitrullinated, and Acetylated Fibrin/Filaggrin Chimeric Peptides.Diagnostics (Basel, Switzerland) · 2024Article
- Multi-Autoantibody Testing Identifies Expansion of Reactivity to Targeted Antigens Before a Diagnosis of Rheumatoid Arthritis.ACR open rheumatology · 2024Article
- Acetylated bacterial proteins as potent antigens inducing an anti-modified protein antibody response.RMD open · 2024Article
- Sequential immunotherapy: towards cures for autoimmunity.Nature reviews. Drug discovery · 2024Review
- Significance of Type II Collagen Posttranslational Modifications: From Autoantigenesis to Improved Diagnosis and Treatment of Rheumatoid Arthritis.International journal of molecular sciences · 2023Review
- Modifiable risk factors linked to the development of rheumatoid arthritis: evidence, immunological mechanisms and prevention.Frontiers in immunology · 2023Review
- Vaccine Can Induce CD4-Mediated Responses to Homocitrullinated PeptidesFrontiers in immunology · 2022Article
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10 authors.
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Abstract
backgroundBesides anti-citrullinated protein antibodies (ACPA), rheumatoid arthritis patients (RA) often display autoantibody reactivities against other post-translationally modified (PTM) proteins, more specifically carbamylated and acetylated proteins. Immunizing mice with one particular PTM results in an anti-modified protein antibody (AMPA) response recognizing different PTM-antigens. Furthermore, human AMPA, isolated based on their reactivity to one PTM, cross-react with other PTMs. However, it is unclear whether the AMPA-reactivity profile is "fixed" in time or whether consecutive exposure to different PTMs can shape the evolving AMPA response towards a particular PTM.
methodsLongitudinally collected serum samples of 8 human individuals at risk of RA and 5 with early RA were tested with ELISA, and titers were analyzed to investigate the evolution of the AMPA responses over time. Mice (13 per immunization group in total) were immunized with acetylated (or carbamylated) protein (ovalbumin) twice or cross-immunized with an acetylated and then a carbamylated protein (or vice versa) and their serum was analyzed for AMPA responses.
resultsHuman data illustrated dynamic changes in AMPA-reactivity profiles in both individuals at risk of RA and in early RA patients. Mice immunized with either solely acetylated or carbamylated ovalbumin (AcOVA or CaOVA) developed reactivity against both acetylated and carbamylated antigens. Irrespective of the PTM-antigen used for the first immunization, a booster immunization with an antigen bearing the other PTM resulted in increased titers to the second/booster PTM. Furthermore, cross-immunization skewed the overall AMPA-response profile towards a relatively higher reactivity against the "booster" PTM.
conclusionsThe relationship between different reactivities within the AMPA response is dynamic. The initial exposure to a PTM-antigen induces cross-reactive responses that can be boosted by an antigen bearing this or other PTMs, indicating the formation of cross-reactive immunological memory. Upon subsequent exposure to an antigen bearing another type of PTM, the overall reactivity pattern can be skewed towards better recognition of the later encountered PTM. These data might explain temporal differences in the AMPA-response profile and point to the possibility that the PTM responsible for the initiation of the AMPA response may differ from the PTM predominantly recognized later in time.
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