{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T06:41:59Z","timestamp":1791096119067,"version":"4.1.0"},"reference-count":74,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2005,12,1]],"date-time":"2005-12-01T00:00:00Z","timestamp":1133395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Human TNF-\u03b1 transgenic (hTNFtg) mice develop erosive arthritis closely resembling rheumatoid arthritis (RA). To investigate mechanisms leading to pathological autoimmune reactions in RA, we examined hTNFtg animals for the presence of RA-associated autoantibodies including Abs to citrullinated epitopes (anti-cyclic citrullinated peptide), heterogeneous nuclear ribonucleoprotein (hnRNP)-A2 (anti-RA33), and heat shock proteins (hsp) (anti-hsp). Although IgM anti-hsp Abs were detected in 40% of hTNFtg and control mice, IgG anti-hsp Abs were rarely seen, and anti-cyclic citrullinated peptide Abs were not seen at all. In contrast, &amp;gt;50% of hTNFtg mice showed IgG anti-RA33 autoantibodies, which became detectable shortly after the onset of arthritis. These Abs were predominantly directed to a short epitope, which was identical with an epitope previously described in MRL\/lpr mice. Incidence of anti-RA33 was significantly decreased in mice treated with the osteoclast inhibitor osteoprotegerin and also in c-fos-deficient mice lacking osteoclasts. Pronounced expression of hnRNP-A2 and a smaller splice variant was seen in joints of hTNFtg mice, whereas expression was low in control animals. Although the closely related hnRNP-A1 was also overexpressed, autoantibodies to this protein were infrequently detected. Because expression of hnRNP-A2 in thymus, spleen, brain, and lung was similar in hTNFtg and control mice, aberrant expression appeared to be restricted to the inflamed joint. Finally, immunization of hTNFtg mice with recombinant hnRNP-A2 or a peptide harboring the major B cell epitope aggravated arthritis. These findings suggest that overproduction of TNF-\u03b1 leads to aberrant expression of hnRNP-A2 in the rheumatoid joint and subsequently to autoimmune reactions, which may enhance the inflammatory and destructive process.<\/jats:p>","DOI":"10.4049\/jimmunol.175.12.8327","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T22:28:10Z","timestamp":1398032890000},"page":"8327-8336","source":"Crossref","is-referenced-by-count":39,"title":["Aberrant Expression of the Autoantigen Heterogeneous Nuclear Ribonucleoprotein-A2 (RA33) and Spontaneous Formation of Rheumatoid Arthritis-Associated Anti-RA33 Autoantibodies in TNF-\u03b1 Transgenic Mice"],"prefix":"10.1093","volume":"175","author":[{"given":"Silvia","family":"Hayer","sequence":"first","affiliation":[{"name":"Department of Rheumatology, Internal Medicine III, Medical University of Vienna , Vienna ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makiyeh","family":"Tohidast-Akrad","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Rheumatology and Balneology , Vienna ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silva","family":"Haralambous","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics, Hellenic Pasteur Institute , Athens ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Jahn-Schmid","sequence":"additional","affiliation":[{"name":"Institute of Pathophysiology, Medical University of Vienna , Vienna ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Skriner","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Internal Medicine III, Medical University of Vienna , Vienna ,","place":["Austria"]},{"name":"Institute of Medical Biochemistry, Medical University of Vienna , Vienna ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Trembleau","sequence":"additional","affiliation":[{"name":"Center of Molecular Medicine of the Austrian Academy of Sciences , Vienna ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He\u0301le\u0300ne","family":"Dumortier","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Cellular Biology, Centre National de la Recherche Scientifique , Strasbourg ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serafin","family":"Pinol-Roma","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Anatomy, Mount Sinai School of Medicine , New York, NY 10029"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt","family":"Redlich","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Internal Medicine III, Medical University of Vienna , Vienna ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Schett","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Internal Medicine III, Medical University of Vienna , Vienna ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylviane","family":"Muller","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Cellular Biology, Centre National de la Recherche Scientifique , Strasbourg ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Kollias","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Biomedical Sciences Research Center \u201cAlexander Fleming,\u201d \u00a0 Vari ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef","family":"Smolen","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Internal Medicine III, Medical University of Vienna , Vienna ,","place":["Austria"]},{"name":"Ludwig Boltzmann Institute for Rheumatology and Balneology , Vienna ,","place":["Austria"]},{"name":"Center of Molecular Medicine of the Austrian Academy of Sciences , Vienna ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gu\u0308nter","family":"Steiner","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Internal Medicine III, Medical University of Vienna , Vienna ,","place":["Austria"]},{"name":"Ludwig Boltzmann Institute for Rheumatology and Balneology , Vienna ,","place":["Austria"]},{"name":"Institute of Medical Biochemistry, Medical University of Vienna , Vienna ,","place":["Austria"]},{"name":"Center of Molecular Medicine of the Austrian Academy of Sciences , Vienna ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2005,12,15]]},"reference":[{"key":"2026020212205602400_R1","first-page":"1245","volume-title":"Nat. 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