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The rheumatoid arthritis-associated autoantigen hnRNP-A2 (RA33) is a major stimulator of autoimmunity in rats with pristane-induced arthritis

Hoffmann, Markus H.; Tuncel, Jonatan LU ; Skriner, Karl; Tohidast-Akrad, Makiyeh; Tuerk, Birgit; Pinol-Roma, Serafin; Serre, Guy; Schett, Georg; Smolen, Josef S. and Holmdahl, Rikard LU , et al. (2007) In Journal of Immunology 179(11). p.7568-7576
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 lgM 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.... (More)
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 lgM 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. (Less)
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Journal of Immunology
volume
179
issue
11
pages
7568 - 7576
publisher
American Association of Immunologists
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  • wos:000251378300045
  • scopus:38849099736
ISSN
1550-6606
language
English
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yes
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65821d8d-a0ec-488b-9cea-da943297d169 (old id 968598)
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http://www.jimmunol.org/cgi/content/abstract/179/11/7568
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2008-01-29 13:50:36
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2017-05-14 04:18:15
@article{65821d8d-a0ec-488b-9cea-da943297d169,
  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 lgM 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.},
  author       = {Hoffmann, Markus H. and Tuncel, Jonatan and Skriner, Karl and Tohidast-Akrad, Makiyeh and Tuerk, Birgit and Pinol-Roma, Serafin and Serre, Guy and Schett, Georg and Smolen, Josef S. and Holmdahl, Rikard and Steiner, Guenter},
  issn         = {1550-6606},
  language     = {eng},
  number       = {11},
  pages        = {7568--7576},
  publisher    = {American Association of Immunologists},
  series       = {Journal of Immunology},
  title        = {The rheumatoid arthritis-associated autoantigen hnRNP-A2 (RA33) is a major stimulator of autoimmunity in rats with pristane-induced arthritis},
  volume       = {179},
  year         = {2007},
}