Anti-citrullinated protein antibodies cause arthritis by cross-reactivity to joint cartilage

• DOI: 10.1172/jci.insight.93688
• Publication Date: 2017-07-05T15:26:07Z
• Authors: Changrong Ge; Dongmei Tong; Bibo Liang; Erik Lönnblom; Nadine Schneider; Cecilia Hagert; Johan Viljanen; Burcu Ayoglu; Roma Stawikowska; Peter Nilsson; Gregg B. Fields; Thomas Skogh; Alf Kastbom; Jan Kihlberg; Harald Burkhardt; Doreen Dobritzsch; Rikard Holmdahl
• Keywords: Citrullination

Today, it is known that autoimmune diseases start a long time before clinical symptoms appear. Anti-citrullinated protein antibodies (ACPAs) appear many years the onset of rheumatoid arthritis (RA). However, still unclear if and how ACPAs are arthritogenic. To better understand molecular basis pathogenicity ACPAs, we investigated autoantibodies reactive against C1 epitope collagen type II (CII) its citrullinated variants. We found these commonly occurring in RA. A mAb (ACC1) was to cross-react with several noncitrullinated epitopes on native CII, causing proteoglycan depletion cartilage severe mice. Structural studies by X-ray crystallography showed such recognition governed shared structural motif "RG-TG" within all epitopes, including electrostatic potential-controlled citrulline specificity. Overall, have demonstrated mechanism explains trigger arthritis.