{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T10:35:19Z","timestamp":1790937319030,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,12,27]],"date-time":"2012-12-27T00:00:00Z","timestamp":1356566400000},"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":[[2013,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Autoantigen presentation by HLA\u2013DR molecules is thought to be a central component of many autoimmune diseases, but identifying disease\u2010relevant autoantigens has been a difficult challenge. In this study we aimed to identify autoantigens in patients with antibiotic\u2010refractory Lyme arthritis, in which infection\u2010induced autoimmunity is thought to play an important role.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using tandem mass spectrometry, naturally presented HLA\u2013DR self peptides from a patient's synovium were identified, synthesized, and reacted with his peripheral blood mononuclear cells (PBMCs). Immunoreactive peptides and their source proteins were then tested for T and B cell responses using large numbers of patient cells or sera.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 120 HLA\u2013DR\u2013presented self peptides identified from one patient, one peptide derived from endothelial cell growth factor (ECGF) caused his PBMCs to proliferate. T and B cell responses to ECGF occurred systemically in \u223c10\u201330% of patients with early or late manifestations of Lyme disease, primarily in those with refractory arthritis\u2013associated HLA\u2013DR alleles, such as DRB1*0101 and 0401. Compared with patients with antibiotic\u2010responsive arthritis, those with antibiotic\u2010refractory arthritis had significantly higher concentrations of ECGF in synovial fluid (<jats:italic>P<\/jats:italic> &lt; 0.0001) and more often had ECGF antibody reactivity. Among non\u2013antibiotic\u2010treated historical patients who developed arthritis, 26% had ECGF reactivity, which often developed before the onset of arthritis and was associated with significantly longer courses of arthritis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>T and B cell responses to ECGF occur in a subset of patients with Lyme disease, particularly in those with antibiotic\u2010refractory arthritis, providing the first direct evidence of autoimmune T and B cell responses in this illness.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.37732","type":"journal-article","created":{"date-parts":[[2012,10,8]],"date-time":"2012-10-08T17:21:04Z","timestamp":1349716864000},"page":"186-196","source":"Crossref","is-referenced-by-count":82,"title":["A novel human autoantigen, endothelial cell growth factor, is a target of T and B cell responses in patients with Lyme disease"],"prefix":"10.1002","volume":"65","author":[{"given":"Elise E.","family":"Drouin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Seward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klemen","family":"Strle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gail","family":"McHugh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kianoosh","family":"Katchar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Londo\u00f1o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunxiang","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine E.","family":"Costello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen C.","family":"Steere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,12,27]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI12634"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1100030"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1004965"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa021933"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200107123450207"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-107-5-725"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780370616"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.22131"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1267"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI58813"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.30384"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.9.6336"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.23135"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.22441"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20052471"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780310405"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5377.703"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2007.04.017"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciq117"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.10772"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.4.2486"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410240406"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00260-07"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01110-06"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2010.03.002"},{"key":"e_1_2_7_27_2","first-page":"1","article-title":"Case definitions for public health surveillance","volume":"39","author":"Wharton M","year":"1990","journal-title":"MMWR Recomm Rep"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.27584"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M110.002477"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2007.11.010"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.178.1.27"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/338557a0"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780370509"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/9858"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1000048"},{"key":"e_1_2_7_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830250553"},{"key":"e_1_2_7_37_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.1.795"},{"key":"e_1_2_7_38_2","first-page":"99","article-title":"Analysis of intestinal HLA\u2010DR bound peptides and dysregulated immune responses to enteric flora in the pathogenesis of inflammatory bowel disease","volume":"11","author":"Oshitani N","year":"2003","journal-title":"Int J Mol Med"},{"key":"e_1_2_7_39_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI32401"},{"key":"e_1_2_7_40_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M900001-MCP200"},{"key":"e_1_2_7_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00048-08"},{"key":"e_1_2_7_42_2","first-page":"1111","article-title":"Plasminogen is required for efficient dissemination of B","volume":"89","author":"Coleman JL","year":"1997","journal-title":"burgdorferi in ticks and for enhancement of spirochetemia in mice. Cell"},{"key":"e_1_2_7_43_2","doi-asserted-by":"publisher","DOI":"10.1086\/653825"},{"key":"e_1_2_7_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2011.02.018"},{"key":"e_1_2_7_45_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.24812"},{"key":"e_1_2_7_46_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.34383"},{"key":"e_1_2_7_47_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.22414"},{"key":"e_1_2_7_48_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201041004"},{"key":"e_1_2_7_49_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.27468"},{"key":"e_1_2_7_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2004.09.001"}],"container-title":["Arthritis &amp; Rheumatism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.37732","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.37732","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T23:14:40Z","timestamp":1696979680000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/art.37732"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,12,27]]},"references-count":49,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2013,1]]}},"alternative-id":["10.1002\/art.37732"],"URL":"https:\/\/doi.org\/10.1002\/art.37732","archive":["Portico"],"relation":{},"ISSN":["0004-3591","1529-0131"],"issn-type":[{"value":"0004-3591","type":"print"},{"value":"1529-0131","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,12,27]]}}}