Anti-citrullinated protein antibodies cause arthritis by cross-reactivity to joint cartilage
| Autor: | Changrong Ge, Dongmei R Tong, Bibo T Liang, Doreen Dobritzsch, Johan Viljanen, Gregg B. Fields, Harald Burkhardt, Alf Kastbom, Erik Lönnblom, Cecilia U Hagert, Thomas Skogh, Jan Kihlberg, Burcu Ayoglu, Peter Nilsson, Roma Stawikowska, Rikard Holmdahl, Nadine Schneider |
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| Přispěvatelé: | Publica |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
musculoskeletal diseases Medicin och hälsovetenskap medicine.drug_class Arthritis ta3111 medicine.disease_cause Monoclonal antibody Medical and Health Sciences Epitope Autoimmunity 03 medical and health sciences 0302 clinical medicine Medicine Biologiska vetenskaper skin and connective tissue diseases 030203 arthritis & rheumatology biology business.industry Cartilage Autoantibody Anti–citrullinated protein antibody General Medicine Biological Sciences ta3121 medicine.disease 3. Good health 030104 developmental biology medicine.anatomical_structure Rheumatoid arthritis Immunology biology.protein business Research Article |
| Popis: | Today, it is known that autoimmune diseases start a long time before clinical symptoms appear. Anti-citrullinated protein antibodies (ACPAs) appear many years before the clinical onset of rheumatoid arthritis (RA). However, it is still unclear if and how ACPAs are arthritogenic. To better understand the molecular basis of pathogenicity of ACPAs, we investigated autoantibodies reactive against the C1 epitope of collagen type II (CII) and its citrullinated variants. We found that these antibodies are commonly occurring in RA. A mAb (ACC1) against citrullinated C1 was found to cross-react with several noncitrullinated epitopes on native CII, causing proteoglycan depletion of cartilage and severe arthritis in mice. Structural studies by X-ray crystallography showed that such recognition is governed by a shared structural motif "RG-TG" within all the epitopes, including electrostatic potential-controlled citrulline specificity. Overall, we have demonstrated a molecular mechanism that explains how ACPAs trigger arthritis. QC 20170811 |
| Databáze: | OpenAIRE |
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