{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T07:51:38Z","timestamp":1789977098769,"version":"4.0.1"},"reference-count":41,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2009,11,30]],"date-time":"2009-11-30T00:00:00Z","timestamp":1259539200000},"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":[[2009,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Arthritis is a prominent manifestation of Lyme disease, which is caused by infection with <jats:italic>Borrelia burgdorferi<\/jats:italic> (Bb). Chronic Lyme arthritis persisting even after antibiotic treatment is linked to HLA\u2013DRB1*0401 (DR4) and related alleles. In contrast, patients whose Lyme arthritis resolves within 3 months postinfection show an increased frequency of HLA\u2013DRB1*1101 (DR11). The aim of this study was to analyze the underlying mechanism by which HLA\u2013DR alleles confer genetic susceptibility or resistance to antibiotic\u2010refractory Lyme arthritis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We generated DR11\u2010transgenic (DR11\u2010Tg) mice on a murine MHCII<jats:sup>\u2212\/\u2212<\/jats:sup> background and compared their immune response to Bb antigens with the response of DR4\u2010Tg mice after immunization with Bb outer surface protein A (OspA) or infection with live Bb.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>T cells from OspA\u2010immunized and Bb\u2010infected DR11\u2010Tg mice had defective production of interferon\u2010\u03b3 as compared with those from DR4\u2010Tg mice. In contrast, DR11\u2010Tg mice developed higher titers of anti\u2010OspA and anti\u2010Bb antibodies, respectively, than did DR4\u2010Tg mice. Consistent with this observation, we found that the Bb\u2010infected DR11\u2010Tg mice had a decreased spirochetal burden as compared with the DR4\u2010Tg mice, as measured by quantitative polymerase chain reaction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study provides direct evidence that in the presence of HLA\u2013DR11, the immune response against Bb antigens is directed toward a protective antibody response. In contrast, an inflammatory Th1 response is induced in the presence of DR4. These observations offer an explanation for the differential genetic susceptibility of DR4+ and DR11+ individuals to the development of chronic Lyme arthritis and, eventually, the progression to antibiotic\u2010refractory Lyme arthritis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.25005","type":"journal-article","created":{"date-parts":[[2009,11,30]],"date-time":"2009-11-30T18:13:25Z","timestamp":1259604805000},"page":"3831-3840","source":"Crossref","is-referenced-by-count":41,"title":["HLA\u2013DR alleles determine responsiveness to <i>Borrelia burgdorferi<\/i> antigens in a mouse model of self\u2010perpetuating arthritis"],"prefix":"10.1002","volume":"60","author":[{"given":"Bettina Panagiota","family":"Iliopoulou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mireia","family":"Guerau\u2010De\u2010Arellano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte 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