A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Anti-citrullinated protein antibodies cause arthritis by cross-reactivity to joint cartilage
Tekijät: Ge CR, Tong DM, Liang BB, Lonnblom E, Schneider N, Hagert C, Viljanen J, Ayoglu B, Stawikowska R, Nilsson P, Fields GB, Skogh T, Kastbom A, Kihlberg J, Burkhardt H, Dobritzsch D, Holmdahl R, Holmdahl R
Kustantaja: AMER SOC CLINICAL INVESTIGATION INC
Julkaisuvuosi: 2017
Journal: JCI Insight
Tietokannassa oleva lehden nimi: JCI INSIGHT
Lehden akronyymi: JCI INSIGHT
Artikkelin numero: ARTN e93688
Vuosikerta: 2
Numero: 13
Sivujen määrä: 19
ISSN: 2379-3708
DOI: https://doi.org/10.1172/jci.insight.93688
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/26036558
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.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
