| First Author | Miranda-Carús ME | Year | 1998 |
| Journal | J Immunol | Volume | 161 |
| Issue | 11 | Pages | 5886-92 |
| PubMed ID | 9834068 | Mgi Jnum | J:51087 |
| Mgi Id | MGI:1314576 | Doi | 10.4049/jimmunol.161.11.5886 |
| Citation | Miranda-Carus ME, et al. (1998) Induction of antibodies reactive with SSA/Ro-SSB/La and development of congenital heart block in a murine model. J Immunol 161(11):5886-92 |
| abstractText | To correlate the arrhythmogenic effects of maternal autoantibodies with the genesis of congenital heart block, female BALB/c mice were immunized with human recombinant 48-kDa SSB/La, 60-kDa SS/Ro, 52-kDa SSA/Ro (52 alpha), and 52 beta (amino acids 169-245 deleted) as well as with murine recombinant 52-kDa SSA/Ro, Control animals received beta-galactosidase or a polypeptide encoded by pET-28 alone, Following primary immunization and two boosters, high titer responses to the respective Ags were established by ELISA, immunoblotting, and immunoprecipitation, Sera from mice immunized with either human 52 alpha or 52 beta immunoprecipitated murine 52Ro, mRNA and protein expression of 52Ro was demonstrated in the newborn murine heart. A spectrum of atrioventricular nodal conduction abnormalities was identified by electrocardiogram, First-degree block was detected in 7% of 27 pups born to mothers immunized with 48La, 20% of 54 pups born to 60Ro-immunized mothers, 6% of 56 pups born to 52 alpha-immunized mothers, 7% of 86 pups born to 52 beta- immunized mothers, and 9% of 22 pups born to mothers immunized with murine 52Ro, Advanced conduction abnormalities were only identified in offspring of 52 alpha- or 52 beta-immunized mice. In the 52 alpha group, one pup had complete block and another had second-degree block (Wenckebach type); in the 52 beta group, five pups had complete block, Maternal Abs to the primary immunogens were detected in the pups, No control had any conduction abnormalities. This Ab-specific animal model provides strong evidence for a pathogenic role of anti-SSA/Ro- SSB/La Abs, particularly 52Ro, in the development of congenital heart block. The range and frequency of conduction defects suggest that additional factors promote disease expression. |
