{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T09:30:15Z","timestamp":1771666215203,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2011,8,31]],"date-time":"2011-08-31T00:00:00Z","timestamp":1314748800000},"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":[[2011,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Congenital heart block (CHB), a manifestation of neonatal lupus, is associated with maternal anti\u2010Ro\/SSA and anti\u2010La\/SSB autoantibodies and recurs in \u223c18% of subsequent pregnancies. This study was undertaken to investigate the effect of the idiotype:antiidiotype (Id:anti\u2010Id) antibody ratio in the ability of intravenous immunoglobulin (IVIG) administered during subsequent pregnancies to prevent CHB.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We studied 16 anti\u2010Ro\/SSA and anti\u2010La\/SSB\u2013positive pregnant women from the Preventive IVIG Therapy for Congenital Heart Block study who had previously given birth to a child with neonatal lupus. In 3 of the mothers, the study pregnancy resulted in the birth of a child with neonatal lupus (2 with CHB and 1 with rash). Sequential serum samples were obtained from all mothers immediately before the administration of IVIG during pregnancy and were evaluated for antibodies against the major B cell epitope 349\u2013364aa of La\/SSB (idiotype) and its antiidiotypic antibodies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Following IVIG treatment, serum titers of anti\u2010La(349\u2013364) (Id antibodies) decreased in 80% of the mothers, and in 60% an increase in anti\u2010Id antibodies against anti\u2010La(349\u2013364) was observed. The Id:anti\u2010Id ratio was significantly higher in mothers whose offspring developed neonatal lupus compared to mothers who gave birth to a healthy child (<jats:italic>P<\/jats:italic> &lt; 0.0001). Removal of anti\u2010Id antibodies substantially increased the reactivity against La(349\u2013364) in sera from 5 of 7 mothers tested. All IVIG preparations were examined for Id and anti\u2010Id antibody activity. IVIG from batches administered to mothers who gave birth to a healthy child had an Id:anti\u2010Id activity ratio of &lt;1, in contrast to that given to mothers who gave birth to a child with neonatal lupus. Addition of the IVIG preparations to the maternal sera further enhanced antiidiotypic activity (by up to 4.7\u2010fold) in 11 of 13 patients studied.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This is the first study in humans to demonstrate that IVIG influences the Id\u2013anti\u2010Id network of a specific pathogenic autoantibody. Specifically, we showed that IVIG enhanced the anti\u2010Id antibody response in pregnant women with anti\u2010La\/SSB antibodies. A high Id:anti\u2010Id ratio in both the IVIG preparation and the maternal serum may explain the absence of an effect of IVIG in preventing recurrent neonatal lupus in some cases.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.30464","type":"journal-article","created":{"date-parts":[[2011,5,25]],"date-time":"2011-05-25T16:03:40Z","timestamp":1306339420000},"page":"2783-2789","source":"Crossref","is-referenced-by-count":31,"title":["Association of the idiotype:antiidiotype antibody ratio with the efficacy of intravenous immunoglobulin treatment for the prevention of recurrent autoimmune\u2010associated congenital heart block"],"prefix":"10.1002","volume":"63","author":[{"given":"John G.","family":"Routsias","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikolaos C.","family":"Kyriakidis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah M.","family":"Friedman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina","family":"Llanos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Clancy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haralampos M.","family":"Moutsopoulos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jill","family":"Buyon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Athanasios G.","family":"Tzioufas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,8,31]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2003.09.002"},{"key":"e_1_2_6_3_2","first-page":"1058","volume-title":"Dubois' lupus erythematosus","author":"Buyon JP","year":"2006"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.2009.02100.x"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1067\/mpd.2003.233"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200108)44:8<1832::AID-ART320>3.0.CO;2-C"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(98)00161-2"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200102)44:2<487::AID-ANR70>3.0.CO;2-D"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.24768"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2008.03732.x"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21954"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.27308"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF03402155"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-8411(03)00063-5"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.11430"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199901213400311"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.157.8.3317"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.9.5345"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.27350"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0800578105"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/347151a0"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.2337\/diab.45.7.926"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.2005.01568.x"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830220706"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1006\/jaut.1995.0032"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.2004.00350.x"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/0952-7915(95)80053-0"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-2478(92)90019-K"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1006\/jaut.2000.0472"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(00)70500-X"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.AOG.0000270302.80336.dd"}],"container-title":["Arthritis &amp; 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