Anti-C1q Antibodies as Occurring in Systemic Lupus Erythematosus Could Be Induced by an Epstein-Barr Virus-Derived Antigenic Site
| Autor: | Csorba, K., Schirmbeck, L.A., Tuncer, E., Ribi, C., Roux-Lombard, P., Chizzolini, C., Huynh-Do, U., Vanhecke, D., Trendelenburg, M. |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Adult
Male lcsh:Immunologic diseases. Allergy Herpesvirus 4 Human Adolescent Immunology anti-C1q antibody chemical and pharmacologic phenomena 610 Medicine & health urologic and male genital diseases Mice Young Adult A08 epitope fluids and secretions systemic lupus erythematosus immune system diseases Animals Humans Lupus Erythematosus Systemic Epstein-Barr virus molecular mimicry skin and connective tissue diseases Original Research Aged Autoantibodies ddc:616 Aged 80 and over C1q deficient mice EBNA-1 autoimmunity Complement C1q Middle Aged Mice Inbred C57BL Epstein-Barr Virus Nuclear Antigens Female lcsh:RC581-607 |
| Zdroj: | Csorba, Kinga; Schirmbeck, Lucia A; Tuncer, Eylul; Ribi, Camillo; Roux-Lombard, Pascale; Chizzolini, Carlo; Huynh-Do, Uyen; Vanhecke, Dominique; Trendelenburg, Marten (2019). Anti-C1q Antibodies as Occurring in Systemic Lupus Erythematosus Could Be Induced by an Epstein-Barr Virus-Derived Antigenic Site. Frontiers in immunology, 10, p. 2619. Frontiers Research Foundation 10.3389/fimmu.2019.02619 Frontiers in Immunology, Vol 10 (2019) Frontiers in Immunology Frontiers in Immunology, Vol. 10 (2019) P. 2619 Frontiers in immunology, vol. 10, pp. 2619 |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2019.02619 |
| Popis: | Previous infection with Epstein-Barr virus (EBV) is believed to trigger autoimmunity and to drive autoantibody generation as occurring in patients with systemic lupus erythematosus (SLE). Complement C1q and autoantibodies targeting it (anti-C1q) are also considered to be involved in the pathogenesis of SLE, independently of the impact of environmental insults. Still, the circumstances under which these autoantibodies arise remain elusive. By studying a major antigenic site of C1q targeted by anti-C1q (A08), we aimed to determine environmental factors and possible mechanisms leading to the development of anti-C1q. First, we determined antigenic residues of A08 that were critical for the binding of anti-C1q; importantly, we found the binding to depend on amino-acid-identity. Anti-C1q of SLE patients targeting these critical antigenic residues specifically cross-reacted with the EBV-related EBNA-1 (Epstein-Barr virus nuclear antigen 1)-derived peptide EBNA348. In a cohort of 180 SLE patients we confirmed that patients that were seropositive for EBV and recognized the EBNA348 peptide had increased levels of anti-A08 and anti-C1q, respectively. The correlation of anti-EBNA348 with anti-A08 levels was stronger in SLE patients than in matched healthy controls. Finally, EBNA348 peptide-immunization of C1q -/- mice induced the generation of cross-reactive antibodies which recognized both the A08 epitope of C1q and intact C1q. These findings suggest that anti-C1q in SLE patients could be induced by an EBV-derived epitope through molecular mimicry, thereby further supporting the pathogenic role of EBV in the development of SLE. Considering the role of C1q and anti-C1q, modifying the anti-EBV response might be a promising strategy to improve the course of the disease. |
| Databáze: | OpenAIRE |
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