Development of synthetic anti‐cyclic citrullinated peptide antibody and its arthritogenic role. Issue 11 (27th November 2015)

• Record Type: Journal Article
• Authors: Kim, Youngkyun; Lee, Jennifer; Jung, Hyerin; Yi, Hyoju; Rim, Yeri Alice; Jung, Seung Min; Ju, Ji Hyeon
• Is Part Of: Clinical & translational immunology. Volume 4:Issue 11 (2015)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2015-11-27
• Subjects: Immunologic diseases -- Periodicals; Immunology -- Periodicals; Clinical medicine -- Periodicals; Immune System Diseases -- therapy; Immunotherapy; Immunologic Factors -- therapeutic use; Translational Medical Research; Molecular Targeted Therapy; Clinical medicine; Immunologic diseases; Immunology; Periodicals; Periodicals; Fulltext; Internet Resources; Periodicals; 616.079
• DOI: 10.1038/cti.2015.24
• Languages: English
• ISSNs: 2050-0068

Abstract

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. Rheumatoid arthritis: A new insight into autoimmunity: Antibodies against modified proteins appear to play a role in rheumatoid arthritis, an autoimmune disease. Citrullinated proteins, in which the amino acid arginine is converted into citrulline, occur in most joints affected by rheumatoid arthritis. Antibodies against these proteins are also found in the joints, but it is not known if these antibodies are a cause or a result of the disease. To clarify this issue, Ji Hyeon Ju and co‐workers at the Catholic University of Korea generated a synthetic antibody against citrullinated proteins and injected it into a mouse model of rheumatoid arthritis. While probably unable to induce arthritis on its own, the antibody was able to exacerbate the pre‐existing arthritis in the mice. Therapies that interfere with the antibodies directed against citrullinated proteins might offer a promising new approach to managing rheumatoid arthritis.