title: Anti-Ro52 monoclonal antibodies specific for amino acid 200-239, but not other Ro52 epitopes, induce congenital heart block in a rat model.
abstract: BACKGROUND
  Congenital heart block (CHB) may develop in fetuses of women with anti-Ro/La autoantibodies following placental transfer of maternal autoantibodies and disruption of the fetal atrioventricular (AV) conduction system. Animal models of CHB currently rely on immunisation or transfer of anti-Ro/La antibodies purified from mothers of children with CHB, which does not allow precise identification of the disease-inducing antibody specificity.
  
  
  OBJECTIVE
  To determine the ability of different anti-Ro52 monoclonal antibodies to induce cardiac electrophysiological abnormalities in vivo and affect the calcium homoeostasis of cardiomyocytes in vitro.
  
  
  METHODS
  Monoclonal antibodies recognising different domains of Ro52 were generated and injected into pregnant rats, and ECG was recorded on newborn pups. Cultures of rat neonatal cardiomyocytes were established to assess the effect of the different anti-Ro52 monoclonal antibodies on calcium homoeostasis.
  
  
  RESULTS
  First-degree AV block and bradycardia developed after maternal transfer of antibodies specific for amino acids 200-239 of Ro52 (p200), while pups exposed to antibodies targeting N- or C-terminal epitopes of Ro52 did not show any electrocardiogram abnormalities. Addition of an anti-p200 antibody to cultured cardiomyocytes induced calcium dyshomoeostasis in a time- and dose-dependent manner, while addition of other Ro52 antibodies had no effect.
  
  
  CONCLUSIONS
  These data for the first time show unambiguously that antibodies specific for amino acids 200-239 of Ro52 can induce cardiac conduction defects in the absence of other autoantibodies, and may therefore be the main initiators of cardiac pathology in the pool of anti-Ro52 antibodies in mothers of children with CHB.
authors.affiliation: Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Ambrosi
authors.forename: Vijole
authors.initials: V
authors.lastname: Dzikaite
authors.forename: Jeongsook
authors.initials: J
authors.lastname: Park
authors.forename: Linn
authors.initials: L
authors.lastname: Strandberg
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Kuchroo
authors.forename: Eric
authors.initials: E
authors.lastname: Herlenius
authors.forename: Marie
authors.initials: M
authors.lastname: Wahren-Herlenius
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology; D054537:Atrioventricular Block / Q000151:congenital* / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D004562:Electrocardiography; D000939:Epitopes / Q000276:immunology; D005260:Female; D006706:Homeostasis / Q000276:immunology; D008431:Maternal-Fetal Exchange / Q000276:immunology; D032383:Myocytes, Cardiac / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology; D051381:Rats; D012261:Ribonucleoproteins / Q000276:immunology*; D000099207:SS-A Antigen
chemical_list: D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D002118:Calcium; D000939:Epitopes; D012261:Ribonucleoproteins; D000099207:SS-A Antigen