{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:39:00Z","timestamp":1791275940230,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2012,7,27]],"date-time":"2012-07-27T00:00:00Z","timestamp":1343347200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2012,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Male rats transgenic for HLA\u2013B27 and human \u03b2<jats:sub>2<\/jats:sub>\u2010microglobulin (h\u03b2<jats:sub>2<\/jats:sub>m) spontaneously develop epididymoorchitis (EO) preceding the development of spondylarthritis (SpA). In the specific B27\/h\u03b2<jats:sub>2<\/jats:sub>m\u2010transgenic rat cross\u2010strain (21\u20103 \u00d7 382\u20102)F<jats:sub>1<\/jats:sub>, only the males develop SpA, and neither sex develops gut inflammation. This study was undertaken to determine whether EO and SpA in male (21\u20103 \u00d7 382\u20102)F<jats:sub>1<\/jats:sub> rats are causally related. In addition, the primary characteristics of EO in this rat arthritis model were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male B27\/h\u03b2<jats:sub>2<\/jats:sub>m\u2010transgenic (21\u20103 \u00d7 382\u20102)F<jats:sub>1<\/jats:sub> rats underwent bilateral, unilateral, or sham epididymoorchiectomy between ages 36 and 125 days. The castrated rats were given testosterone replacement. Alternatively, the 21\u20103 and 283\u20102 transgene loci were crossed with a transgene inducing aspermatogenesis. Rats were observed for the development of EO, arthritis, and spondylitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In unmanipulated transgenic rats, inflammation was first evident in the ductuli efferentes (DE; ducts linking the rete testis to epididymis) as early as age 30 days. The inflammation was initially neutrophilic, and later became granulomatous. Antisperm and anti\u2013testis cell antibodies appeared in the rat serum after age 70 days. Cells infiltrating the testes were predominantly CD4+ T cells and CD68+ or CD163+ macrophages. Quantitative polymerase chain reaction of the DE, epididymis, and testis showed elevations in the levels of interferon\u2010\u03b3, interleukin\u201010 (IL\u201010), and IL\u201017A. In addition, levels of IL\u201012A, IL\u201022, IL\u201023A, and IL\u201023 receptor were found to be elevated in the DE. Remarkably, castration of the rats before age 91 days completely prevented the subsequent onset of arthritis and spondylitis, as did transgene\u2010induced azospermia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Autoimmune EO develops spontaneously in HLA\u2013B27\/h\u03b2<jats:sub>2<\/jats:sub>m\u2013transgenic (21\u20103 \u00d7 283\u20102)F<jats:sub>1<\/jats:sub> rats at age 30 days, the age when antigen\u2010positive meiotic germ cells first exit the testis. Persistent testicular inflammation and\/or antigenic stimulation are essential prerequisites for the subsequent development of SpA. Thus, dysregulated innate immunity at immune\u2010privileged sites may be an essential mechanism triggering the onset of SpA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.34480","type":"journal-article","created":{"date-parts":[[2012,4,5]],"date-time":"2012-04-05T17:10:56Z","timestamp":1333645856000},"page":"2518-2528","source":"Crossref","is-referenced-by-count":37,"title":["Autoimmune epididymoorchitis is essential to the pathogenesis of male\u2010specific spondylarthritis in HLA\u2013B27\u2013transgenic rats"],"prefix":"10.1002","volume":"64","author":[{"given":"Joel D.","family":"Taurog","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Rival","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonie M.","family":"van Duivenvoorde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nimman","family":"Satumtira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha L.","family":"Dorris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Shelton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A.","family":"Richardson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. 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