Author/Editor     van Beers, Joyce J. B. C.; Schwarte, Carla M.; Stammen-Vogelzangs, Judith; Oosterink, Els; Božič, Borut; Pruijn, Ger J. M.
Title     The rheumatoid arthritis synovial fluid citrullinome reveals novel citrullinated epitopes in apolipoprotein E, myeloid nuclear differentiation antigen, and ß-actin
Type     članek
Vol. and No.     Letnik 65, št. 1
Publication year     2013
Volume     str. 69-80
ISSN     0004-3591 - Arthritis and rheumatism
Language     eng
Abstract     To generate a catalog of citrullinated proteins that are present inthe synovia of patients with rheumatoid arthritis (RA) and to elucidate their relevance for the anti-citrullinated protein antibody response in RA. Polypeptides isolated from the synovial fluid of patients with RA were identified by mass spectrometry. Three proteins (apolipoprotein E [Apo E], myeloid nuclear differentiation antigen [MNDA], and ß-actin) were studied in more detail, using immunoprecipitation and Western blotting. The presence of autoantibodies to synthetic peptides derived from these proteins in sera from patients with RA, sera from patients with other diseases, and sera from healthy control subjects was studied by enzyme-linked immunosorbent assay (ELISA). Results RA synovial fluid samples displayed several distinct patterns of citrullinated proteins. Using mass spectrometry, (fragments of) 192 proteins were identified, including 53 citrullinated proteins, some of which contained multiple citrullinated residues. In addition to previously reported citrullinated proteins in RA synovia (e.g., vimentin and fibrinogen),a series of novel citrullinated proteins, including Apo E, MNDA, ß-actin, and cyclophilin A, was identified. Immunoprecipitation experiments confirmed the citrullination of Apo E and MNDA. ELISAs demonstrated the presence of autoreactive citrullinated epitopes in Apo E, MNDA, and Ž-actin. Synovial fluid samples from the inflamed joints of patients with RA contain many citrullinated proteins. Citrullinated Apo E, MNDA, and ß-actinare novel antigens identified in RA synovial fluid, and only a limited number of their citrullinated epitopes are targeted by the immune system in RA.
Descriptors     revmatoidni artritis
Keywords     synovial fluid
rheumatoid arthritis
polypeptides
autoimmune disease
avtoimunske bolezni
polipeptidi
sinovialna tekočina