{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T09:50:55Z","timestamp":1760608255305},"reference-count":27,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2005,11,30]],"date-time":"2005-11-30T00:00:00Z","timestamp":1133308800000},"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":[[2005,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Opsonization of apoptotic cells by autoantibodies bound to surface membrane\u2013translocated La\/SSB antigens may initiate tissue damage in the setting of congenital heart block. By injecting pregnant mice with human anti\u2010La antibodies, we previously demonstrated the formation of IgG\u2013apoptotic cell complexes in the developing mouse fetus; however, the binding of anti\u2010La antibodies to human\u2010specific epitopes could not be addressed. Accordingly, the objective of the current study was to delineate the epitope specificity of human La antibodies that are exposed on the surface of apoptotic cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used fluorescence microscopy and flow cytometry to assess the binding of human anti\u2010La antibodies affinity purified against immunodominant epitopes of La to human cells undergoing spontaneous apoptosis, in a murine xenograft model in vivo and in cultured human fetal cardiocytes rendered apoptotic in vitro, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Anti\u2010La antibodies bound to immunodominant epitopes of La within the NH<jats:sub>2<\/jats:sub>\u2010terminus and the RNA recognition motif (RRM) region of apoptotic human cells, in both xenografts and fetal cardiocytes. In contrast, human antibodies affinity purified against the COOH\u2010terminal La epitope did not bind apoptotic cells in either model. This defines the topology of redistributed La during apoptosis, with surface exposure of the NH<jats:sub>2<\/jats:sub>\u2010terminus and RRM regions. The potential importance of anti\u2010La NH<jats:sub>2<\/jats:sub>\u2010terminal and anti\u2010La RRM specificity was confirmed by detection of this reactivity in mothers of children with congenital heart block.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings provide insight into both the molecular modification of the La autoantigen during apoptosis and the specificity of antibodies capable of binding to surface\u2010exposed La. Subsequent formation of surface immune complexes may lead to tissue injury in patients with autoimmune diseases such as congenital heart block.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.21486","type":"journal-article","created":{"date-parts":[[2005,12,1]],"date-time":"2005-12-01T18:24:43Z","timestamp":1133461483000},"page":"3934-3942","source":"Crossref","is-referenced-by-count":29,"title":["Exposure and binding of selected immunodominant La\/SSB epitopes on human apoptotic cells"],"prefix":"10.1002","volume":"52","author":[{"given":"Petra J.","family":"Neufing","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert M.","family":"Clancy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael W.","family":"Jackson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hai Bac","family":"Tran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jill P.","family":"Buyon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom P.","family":"Gordon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,11,30]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.9.5345"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2003.09.002"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.10316"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.11430"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0896-8411(91)90015-5"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.10552"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116617"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780350609"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1998.tb01222.x"},{"key":"e_1_2_6_11_2","first-page":"3814","article-title":"Transplantation of human prostatic carcinoma into nude mice in Matrigel","volume":"51","author":"Pretlow TG","year":"1991","journal-title":"Cancer Res"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780360309"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2003.12.015"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.3.875"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(85)90184-X"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1191\/096120398678919606"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1191\/0961203304lu1010xx"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.4.2156"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.161.9.5061"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M003673200"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4400571"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115762"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.1995.tb02274.x"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1089\/152308604322899332"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.16.9935"},{"key":"e_1_2_6_26_2","doi-asserted-by":"crossref","first-page":"6931","DOI":"10.1016\/S0021-9258(18)48333-0","article-title":"Characterization of Ca2+\u2010dependent phospholipid binding and phosphorylation of lipocortin I","volume":"262","author":"Schlaepfer DD","year":"1987","journal-title":"J Biol Chem"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(03)00090-X"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20020186"}],"container-title":["Arthritis &amp; 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