title: The rheumatoid arthritis-associated autoantigen hnRNP-A2 (RA33) is a major stimulator of autoimmunity in rats with pristane-induced arthritis.
abstract: A single intradermal injection of the mineral oil pristane in susceptible DA.1F rats induces erosive arthritis closely mimicking rheumatoid arthritis (RA). Pristane-induced arthritis (PIA) is driven by autoreactive T cells but no autoantigen has been identified to date. We therefore analyzed B and T cell responses to autoantigens potentially involved in the pathogenesis of RA, including IgG, citrullinated proteins, stress proteins, glucose-6-phosphate isomerase, and heterogeneous nuclear ribonucleoprotein (hnRNP)-A2 (RA33). IgG and IgM autoantibodies to hnRNP-A2 were detectable in sera of pristane-primed DA.1F rats already 1 wk before disease onset, reached maximum levels during the acute phase, and correlated with arthritis severity. Apart from rheumatoid factor, autoantibodies to other Ags were not observed. CD4(+) lymph node cells isolated 10 days after pristane injection produced IFN-gamma but not IL-4 in response to stimulation with hnRNP-A2, whereas none of the other candidate Ags elicited cytokine secretion. Surprisingly, hnRNP-A2 also stimulated lymph node cells of naive animals to produce inflammatory cytokines in a MyD88-dependent manner. Furthermore, hnRNP-A2 was highly overexpressed in the joints of rats injected with pristane. Overexpression coincided with the appearance of anti-RA33 Abs and preceded the onset of clinical symptoms of PIA by several days. Taken together, these data suggest hnRNP-A2 to be among the primary inducers of autoimmunity in PIA. Therefore, this Ag might play a pivotal role in the pathogenesis of PIA and possibly also human RA.
authors.affiliation: Department of Rheumatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Markus H
authors.initials: MH
authors.lastname: Hoffmann
authors.forename: Jonatan
authors.initials: J
authors.lastname: Tuncel
authors.forename: Karl
authors.initials: K
authors.lastname: Skriner
authors.forename: Makiyeh
authors.initials: M
authors.lastname: Tohidast-Akrad
authors.forename: Birgit
authors.initials: B
authors.lastname: Türk
authors.forename: Serafin
authors.initials: S
authors.lastname: Pinol-Roma
authors.forename: Guy
authors.initials: G
authors.lastname: Serre
authors.forename: Georg
authors.initials: G
authors.lastname: Schett
authors.forename: Josef S
authors.initials: JS
authors.lastname: Smolen
authors.forename: Rikard
authors.initials: R
authors.lastname: Holmdahl
authors.forename: Günter
authors.initials: G
authors.lastname: Steiner
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001324:Autoantigens / Q000235:genetics / Q000276:immunology; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000235:genetics / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D051381:Rats; D017207:Rats, Sprague-Dawley; D013601:T-Lymphocytes / Q000276:immunology; D013729:Terpenes
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D013729:Terpenes; C439768:hnRNP A2; C009042:pristane; D007371:Interferon-gamma