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Relationship between maternal and neonatal levels of antibodies to 48 kDa SSB(La), 52 kDa SSA(Ro), and 60 kDa SSA(Ro) in pregnancies complicated by congenital heart block
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A serologic marker for fetal risk of congenital heart block
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Salomonsson S, Dörner T, Theander E, et al.: A serologic marker for fetal risk of congenital heart block. Arthritis Rheum 2002, 46:1233-1241.
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•• Salomonsson S, Sonesson SE, Ottosson L, et al.: Ro/SSA autoantibodies directly bind cardiomyocytes, disturb calcium homeostasis, and mediate congenital heart block. J Exp Med 2005, 201:11-17. A study with clinical and basic components: prospective serial echocardiography of 25 pregnant women with anti-Ro52 antibodies, induction of first-degree atrioventricular block in 20% of pups born to mice immunized with the Ro p200 peptide, demonstration of p200 antibody binding to cell surface, and disruption of calcium homeostasis in neonatal rat cardiomyocytes cultured in vitro.
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•• Salomonsson S, Sonesson SE, Ottosson L, et al.: Ro/SSA autoantibodies directly bind cardiomyocytes, disturb calcium homeostasis, and mediate congenital heart block. J Exp Med 2005, 201:11-17. A study with clinical and basic components: prospective serial echocardiography of 25 pregnant women with anti-Ro52 antibodies, induction of first-degree atrioventricular block in 20% of pups born to mice immunized with the Ro p200 peptide, demonstration of p200 antibody binding to cell surface, and disruption of calcium homeostasis in neonatal rat cardiomyocytes cultured in vitro.
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Anti-SSA/Ro 52 autoantibodies blocking the cardiac 5-HT4 serotoninergic receptor could explain neonatal lupus congenital heart block
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Cardiac 5-HT4 serotoninergic receptors, 52 K D SSA/Ro and autoimmune-associated congenital heart block
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Buyon JP, Clancy R, Di Donato F, et al.: Cardiac 5-HT4 serotoninergic receptors, 52 K D SSA/Ro and autoimmune-associated congenital heart block. J Autoimmun 2002, 19:79-86.
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•• Kamel R, Eftekhari P, Clancy R, et al, Autoantibodies against the serotoninergic 5-HT4 receptor and congenital heart block: a reassessment. J Autoimmun 2005, 25:72-76. A joint evaluation undertaken cooperatively by two groups whose previous findings had apparently contradicted each other. Sera from 128 patients were assessed in a single blind test using an enzyme-linked immunosorbent assay coated with a 5-HT4 receptor-derived peptide. Discrepancies between previous observations by the two groups could be ascribed to small differences in the set-up of the assay. Although 5-HT4 receptor autoantibodies do not have the predictive value of anti-Ro52 autoantibodies, the presence of these antibodies in a minor subset of mothers whose children have CHB suggests an additional risk factor that may contribute to the pathogenesis of disease
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4 receptor autoantibodies do not have the predictive value of anti-Ro52 autoantibodies, the presence of these antibodies in a minor subset of mothers whose children have CHB suggests an additional risk factor that may contribute to the pathogenesis of disease.
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Friedman DM, Kim MY, Copel JA, et al.: Utility of cardiac monitoring in fetuses at risk of congenital heart block: The PR interval and dexamethasone evaluation (PRIDE) prospective study [abstract]. Arthritis Rheum 2006, 54(Suppl):S689.
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•• Clancy RM, Buyon JP, Ikeda K, et al.: Maternal antibody responses to the 52-kd SSA/Ro p200 peptide and the development of fetal conduction defects. Arthritis Rheum 2005, 52:3079-3086. Evaluation of anti-p200 reactivity in sera of 156 subjects and analysis of correlation to clinical history. Interpretation of these data is that reactivity to p200 is a dominant but not uniform anti-Ro52 response in women whose children have CHB. Because exposure to this antibody specificity was observed with a similar frequency in children without CHB born to mothers with anti-Ro52, additional factors are necessary to convert risk to disease expression.
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•• Clancy RM, Buyon JP, Ikeda K, et al.: Maternal antibody responses to the 52-kd SSA/Ro p200 peptide and the development of fetal conduction defects. Arthritis Rheum 2005, 52:3079-3086. Evaluation of anti-p200 reactivity in sera of 156 subjects and analysis of correlation to clinical history. Interpretation of these data is that reactivity to p200 is a dominant but not uniform anti-Ro52 response in women whose children have CHB. Because exposure to this antibody specificity was observed with a similar frequency in children without CHB born to mothers with anti-Ro52, additional factors are necessary to convert risk to disease expression.
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•• Glickstein J, Buyon J, Kim M, et al.: The fetal Doppler mechanical PR interval: A validation study. Fetal Diagn Ther 2004, 19:31-34. Echocardiograms on 75 healthy fetuses were performed and evaluated by 15 pediatric cardiologists participating in a larger clinical trial involving fetuses at risk for autoantibody-associated CHB. After viewing a teaching tape, each physician measured the pulsed Doppler-derived fetal PR interval on five different subjects. The tapes were sent to a central facility and the same intervals were remeasured by an experienced central reader, who concluded that the pulsed Doppler assessment of the mechanical PR interval in the fetus can be accurately performed after minimal training.
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•• Glickstein J, Buyon J, Kim M, et al.: The fetal Doppler mechanical PR interval: A validation study. Fetal Diagn Ther 2004, 19:31-34. Echocardiograms on 75 healthy fetuses were performed and evaluated by 15 pediatric cardiologists participating in a larger clinical trial involving fetuses at risk for autoantibody-associated CHB. After viewing a teaching tape, each physician measured the pulsed Doppler-derived fetal PR interval on five different subjects. The tapes were sent to a central facility and the same intervals were remeasured by an experienced central reader, who concluded that the pulsed Doppler assessment of the mechanical PR interval in the fetus can be accurately performed after minimal training.
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•• Sonesson SE, Salomonsson S, Jacobsson LA, et al.: Signs of first-degree heart block occur in one-third of fetuses of pregnant women with anti-SSA/Ro 52-kd antibodies. Arthritis Rheum 2004, 50:1253-1261. A prospective study using two different methods to measure the mechanical Doppler PR interval serially in 24 anti-Ro/La antibody-positive women between 18 and 24 weeks of gestation, in comparison with 284 control pregnant women.
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•• Sonesson SE, Salomonsson S, Jacobsson LA, et al.: Signs of first-degree heart block occur in one-third of fetuses of pregnant women with anti-SSA/Ro 52-kd antibodies. Arthritis Rheum 2004, 50:1253-1261. A prospective study using two different methods to measure the mechanical Doppler PR interval serially in 24 anti-Ro/La antibody-positive women between 18 and 24 weeks of gestation, in comparison with 284 control pregnant women.
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• Rein AJ, Mevorach D, Pedes Z, et al.: Fetal first-degree heart block, or where to set the confidence limit [Comment on Arthritis Rheum 2004, 50:1253-1261.]. Arthritis Rheum 2005, 52:366. The authors agree with Sonesson et al. [28••] that introducing the novel method of utilizing superior vena cava-aorta recordings to measure atrioventricular conduction in the fetus is important, but they suggest a higher limit in defining first-degree heart block.
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• Rein AJ, Mevorach D, Pedes Z, et al.: Fetal first-degree heart block, or where to set the confidence limit [Comment on Arthritis Rheum 2004, 50:1253-1261.]. Arthritis Rheum 2005, 52:366. The authors agree with Sonesson et al. [28••] that introducing the novel method of utilizing superior vena cava-aorta recordings to measure atrioventricular conduction in the fetus is important, but they suggest a higher limit in defining first-degree heart block.
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• Buyon JP, Askanase AD, Kim MY, et al, On identifying an early marker for congenital heart block: when is a long PR interval too long, Comment on Arthritis Rheum 2004, 50:1253-1261, Arthritis Rheum 2005, 52:1341-1342. These authors also question the definition of first-degree block, noting that of the eight fetuses with signs of first-degree block described by Sonesson et al, 28••, only three had PR intervals greater than 150 milliseconds, and these included the two fetuses that progressed to having more advanced degrees of block. Of particular interest is the case of first-degree block (atrioventricular interval > 150 milliseconds) that progressed to second-degree block but which, after dexamethasone therapy, reverted to first-degree block at birth and normal sinus rhythm within weeks. This finding supports the notion that a threshold may exist in the cascade to fibrosis, below which reversibility is possible
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• Buyon JP, Askanase AD, Kim MY, et al.: On identifying an early marker for congenital heart block: when is a long PR interval too long? [Comment on Arthritis Rheum 2004, 50:1253-1261.] Arthritis Rheum 2005, 52:1341-1342. These authors also question the definition of first-degree block, noting that of the eight fetuses with signs of first-degree block described by Sonesson et al. [28••], only three had PR intervals greater than 150 milliseconds, and these included the two fetuses that progressed to having more advanced degrees of block. Of particular interest is the case of first-degree block (atrioventricular interval > 150 milliseconds) that progressed to second-degree block but which, after dexamethasone therapy, reverted to first-degree block at birth and normal sinus rhythm within weeks. This finding supports the notion that a threshold may exist in the cascade to fibrosis, below which reversibility is possible.
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Prenatal diagnosis of fetal complete atrioventricular block with QT prolongation and alternating ventricular pacemakers using multi-channel magnetocardiography and current-arrow maps
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•• Jaeggi ET, Fouron JC, Silverman ED, et al.: Transplacental fetal treatment improves the outcome of prenatally diagnosed complete atrioventricular block without structural heart disease. Circulation 2004, 110:1542-1548. Analysis of 37 cases of complete atrioventricular block managed between 1990 and 2003. Twenty-two were treated (21 with maternal dexamethasone, eight of whom also received B-adrenergic stimulation, and one with B-adrenergic stimulation only), and 15 were untreated. One-year survival was 90% for the dexamethasone-treated group and 46% for those not receiving dexamethasone (P < 0.02).
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•• Jaeggi ET, Fouron JC, Silverman ED, et al.: Transplacental fetal treatment improves the outcome of prenatally diagnosed complete atrioventricular block without structural heart disease. Circulation 2004, 110:1542-1548. Analysis of 37 cases of complete atrioventricular block managed between 1990 and 2003. Twenty-two were treated (21 with maternal dexamethasone, eight of whom also received B-adrenergic stimulation, and one with B-adrenergic stimulation only), and 15 were untreated. One-year survival was 90% for the dexamethasone-treated group and 46% for those not receiving dexamethasone (P < 0.02).
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• Breur JM, Visser GH, Kruize AA, et al.: Treatment of fetal heart block with maternal steroid therapy: case report and review of the literature. Ultrasound Obstet Gynecol 2004, 24:467-472. Case report of one pregnancy in an anti-Ro/La-positive woman receiving dexamethasone, which did not prevent CHB in the fetus and resulted in adverse effects. Also a meta-analysis of 15 previously published reports of 93 cases of fetal CHB treated with maternal steroids.
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• Breur JM, Visser GH, Kruize AA, et al.: Treatment of fetal heart block with maternal steroid therapy: case report and review of the literature. Ultrasound Obstet Gynecol 2004, 24:467-472. Case report of one pregnancy in an anti-Ro/La-positive woman receiving dexamethasone, which did not prevent CHB in the fetus and resulted in adverse effects. Also a meta-analysis of 15 previously published reports of 93 cases of fetal CHB treated with maternal steroids.
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