Seropositivity and Antibody Profiling of Patients Are Dramatically Impacted by the Features of Peptides Used as Immunosorbents: A Lesson from Anti–Citrullinated Protein/Peptide Antibody
Autor: | Cornillet, Martin, Babos, Fruzsina, Magyar, Anna, Sebbag, Mireille, Verrouil, Evelyne, Hudecz, Ferenc, Serre, Guy, Nogueira, Leonor |
---|---|
Přispěvatelé: | Unité différenciation épidermique et auto-immunité rhumatoïde (UDEAR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], Eötvös Loránd University |
Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
MESH: Humans
MESH: Serology / methods MESH: Enzyme-Linked Immunosorbent Assay MESH: Immunosorbents / chemistry MESH: Peptides / immunology MESH: Anti-Citrullinated Protein Antibodies / metabolism MESH: Epitopes / chemistry MESH: Fibrin / immunology MESH: Fibrin / chemistry MESH: Arthritis Rheumatoid / immunology MESH: Epitopes / immunology [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases MESH: Peptides / chemistry MESH: Diagnostic Errors MESH: Immunity Humoral MESH: Citrullination |
Zdroj: | Journal of Immunology Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2018, 201 (11), pp.3211-3217. ⟨10.4049/jimmunol.1800330⟩ |
ISSN: | 0022-1767 1550-6606 |
Popis: | International audience; Quantification of Abs toward a single epitope is critical to understanding immunobiological processes. In autoimmunity, the prognostic value of the serological profiles of patients draws much attention, but the detection of Abs toward a single epitope is not well controlled. Particularly, the rheumatoid arthritis (RA)-specific anti-citrullinated protein/peptide Abs (ACPA) are specific to a two-atom change on arginyl residues and are considered a heterogeneous family of Abs. As a model, we studied ACPA to decipher how peptide features used as immunosorbent impact Ab detection. We synthesized 30 peptides encompassing immunodominant epitopes of citrullinated fibrin differing by their length and biotin location and tested them using ELISA with 120 sera from RA and non-RA rheumatic disease controls, generating over 3000 experimental measurements. We showed that minor molecular changes in peptide chemical structure had dramatic consequences. Even when peptides exhibited the same epitope, measured Ab titers were extremely variable, and patients' seropositivity was discordant in up to 50% of cases. The distance between epitope and biotin was the most critical parameter for efficient Ab detection irrespective of biotin position or peptide length. Finally, we identified a 15-mer peptide bearing a single citrullinated epitope detecting almost all ACPA-positive sera, thus revealing a high degree of homogeneity in RA autoimmune response. This integrative analysis deciphers the dramatic impact of the molecular design of peptide-based technologies for epitope-specific Ab quantification. It provides a model for assay development and highlights that the studies using such technologies can give a wrong perception of biological processes and therefore that medical use of data must be cautious. |
Databáze: | OpenAIRE |
Externí odkaz: |