Cardiac 5-HT4 serotoninergic receptors, 52 kD SSA/Ro and autoimmune-associated congenital heart block

It was recently reported that sera from patients with systemic lupus erythematosus contain antibodies reactive with the second extracellular loop of the serotoninergic 5-HT4 receptor expressed in the human heart. This antibody response was associated with antibodies to 52 kD SSA/Ro, a reactivity prevalent in mothers of children with congenital heart block (CHB). The current study was undertaken to determine whether the 5-HT4 receptor is a tar-et of the immune response in these mothers. Initial experiments demonstrated mRNA expression of the 5-HT4 receptor in the human foetal atrium. Electrophysiologic studies established that human foetal atrial cells express functional 5-HT4 receptors. Sera from 116 mothers enrolled in the Research Registry for Neonatal Lupus, whose children have CHB, were evaluated. Ninety-nine (85%) of these maternal sera contained antibodies to SSA/Ro, 84% of which were reactive with the 52 kD SSA/Ro component by immunoblot. None of the 116 sera were reactive with the peptide spanning aa165-185 of the serotoninergic receptor. Rabbit antisera which recognized this peptide did not react with 52 kD SSA/Ro or peptide aa365-382 in the C terminus. Although 5-HT4 receptors are present and functional in the human foetal heart, maternal antibodies to the 5-HT4 receptor are not associated with the development of CHB. (C) 2002 Elsevier science Ltd. All rights reserved.