title: Development of synthetic anti-cyclic citrullinated peptide antibody and its arthritogenic role.
abstract: This study was undertaken to develop a novel anti-citrullinated peptide antibody (ACPA) and to investigate its arthritogenicity in a collagen-induced arthritis (CIA) model. The novel ACPA, 12G1, was developed by injecting cyclic citrullinated antigen in mice and subsequently hybridizing the B cells producing citrullinated peptide-specific antibodies with a myeloma cell line. The arthritic joints of mice with CIA and collagen antibody-induced arthritis (CAIA) as well as interleukin-1 receptor antagonist (IL-1Ra) knockout (KO) mice were stained immunohistochemically using the 12G1 antibody. Confocal immunostaining was used to identify colocalization of 12G1 with various citrullinated proteins. 12G1 in the presence or absence of chelating beads was administered to CIA mice on days 21 and 28 after type II collagen (CII) immunization to investigate 12G1 arthritogenecity. 12G1 detected citrullinated proteins in the arthritic joints of all the experimental arthritis models used. Confocal immunostaining showed that 12G1 was colocalized with well-known citrullinated proteins, including vimentin, collagen, anti-immunoglobulin binding protein and fibronectin. Staining of citrullinated proteins using 12G1 was more diffuse in CIA mice compared with CAIA and IL-1Ra KO mice. 12G1 injection apparently acted as a booster of immunization in CIA mice in combination with a single CII immunization, with this effect being abolished when 12G1 was injected with chelating beads. The novel ACPA, 12G1, identified various citrullinated proteins in the arthritic joints of three experimental arthritis models. 12G1-treated mice developed arthritis following a single CII immunization, suggesting an arthritogenic potential for ACPA in CIA mice.
authors.affiliation: CiSTEM Laboratory, Convergent Research Consortium for Immunologic Disease, College of Medicine, Seoul St Mary's Hospital, The Catholic University of Korea , Seoul, Republic of Korea.
authors.forename: Youngkyun
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea , Seoul, Republic of Korea.
authors.forename: Jennifer
authors.identifier: 0000-0001-6873-6629
authors.initials: J
authors.lastname: Lee
authors.affiliation: CiSTEM Laboratory, Convergent Research Consortium for Immunologic Disease, College of Medicine, Seoul St Mary's Hospital, The Catholic University of Korea , Seoul, Republic of Korea.
authors.forename: Hyerin
authors.initials: H
authors.lastname: Jung
authors.affiliation: CiSTEM Laboratory, Convergent Research Consortium for Immunologic Disease, College of Medicine, Seoul St Mary's Hospital, The Catholic University of Korea , Seoul, Republic of Korea.
authors.forename: Hyoju
authors.initials: H
authors.lastname: Yi
authors.affiliation: CiSTEM Laboratory, Convergent Research Consortium for Immunologic Disease, College of Medicine, Seoul St Mary's Hospital, The Catholic University of Korea , Seoul, Republic of Korea.
authors.forename: Yeri Alice
authors.initials: YA
authors.lastname: Rim
authors.affiliation: CiSTEM Laboratory, Convergent Research Consortium for Immunologic Disease, College of Medicine, Seoul St Mary's Hospital, The Catholic University of Korea , Seoul, Republic of Korea ; Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea , Seoul, Republic of Korea.
authors.forename: Seung Min
authors.initials: SM
authors.lastname: Jung
authors.affiliation: CiSTEM Laboratory, Convergent Research Consortium for Immunologic Disease, College of Medicine, Seoul St Mary's Hospital, The Catholic University of Korea , Seoul, Republic of Korea ; Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea , Seoul, Republic of Korea.
authors.forename: Ji Hyeon
authors.initials: JH
authors.lastname: Ju