Background Antibodies against citrullinated peptides are specific to rheumatoid arthritis (RA), although its pathologic relevance has not been clearly understood.
Objectives This study was undertaken to develop a novel anti-citrullinated petide antibody (ACPA) and to investigate the arthritogenecity of the ACPA in collagen-induced arthritis (CIA) model, the commonly used murine model of RA.
Methods The novel ACPA, 12G1 was developed by injecting cyclic citrullinated antigen to mice and subsequently hybridizing the B cells producing citrullinated peptide-specific antibodies with myeloma cell line. Arthritic joints of mice with CIA and collagen antibody induced arthritis (CAIA) and IL-1Ra knockout mice underwent immunohistochemical staining with 12G1 antibody, and the staining pattern was compared. Confocal immunostaining was used to identify co-localization of 12G1 with various citrullinated peptides. 12G1 in the presence or absence of chelating bead was administered to mice with CIA on day 21 and 28 after type II collagen (CII) immunization to investigate the arthritogenecity of 12G1.
Results 12G1 could detect citrullinated peptides in the arthritic joints of various experimental arthritis models. On confocal immunostaining of arthritic joints with 12G1, it was found to be co-localized with well-known citrullintaed peptides including vimentin, collagen, anti-immunoglobulin binding protein (BiP), and fibronectin. There was no difference in the staining pattern of citrullinated peptides between the different arthritis models. The injection 12G1 apparently showed comparable effect of a booster immunization in CIA mice with single immunization of CII, which was abolished when 12G1 was injected with chelating beads.
Conclusions The novel ACPA, 12G1 identified various citrullinated peptides in the arthritic joints of various experimental arthritis models. 12G1-treated mice develop arthritis with single immunization of CII, which suggested arthritogenic potential of ACPA in CIA mice.
Sakkas, L. I., et al. (2014). Anti-citrullinated peptides as autoantigens in rheumatoid arthritis-relevance to treatment. Autoimmun Rev 13(11): 1114-1120.
Vossenaar, E. R., et al. (2003). Citrullination of synovial proteins in murine models of rheumatoid arthritis. Arthritis Rheum 48(9): 2489-2500.
Disclosure of Interest None declared
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