Cardiac 5-HT(4) serotoninergic receptors, 52kD 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-HT(4) receptor expressed in the human heart. This antibody response was associated with antibodies to 52kD SSA/Ro, a reactivity prevalent in mothers of children with congenital heart block (CHB). The current study was undertaken to determine whether the 5-HT(4) receptor is a target of the immune response in these mothers. Initial experiments demonstrated mRNA expression of the 5-HT(4) receptor in the human foetal atrium. Electrophysiologic studies established that human foetal atrial cells express functional 5-HT(4) 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 52kD 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 52kD SSA/Ro or peptide aa365-382 in the C terminus. Although 5-HT(4) receptors are present and functional in the human foetal heart, maternal antibodies to the 5-HT(4) receptor are not associated with the development of CHB.
D000906:Antibodies / Q000276:immunology; D001324:Autoantigens; D015551:Autoimmunity / Q000276:immunology*; D005260:Female; D005333:Fetus / Q000276:immunology; D006327:Heart Block / Q000276:immunology*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D009206:Myocardium / Q000276:immunology; D020733:RNA, Small Cytoplasmic; D011985:Receptors, Serotonin / Q000276:immunology* / Q000378:metabolism; D012261:Ribonucleoproteins / Q000276:immunology*; D012859:Sjogren's Syndrome / Q000276:immunology; D000099207:SS-A Antigen
D000906:Antibodies; D001324:Autoantigens; D020733:RNA, Small Cytoplasmic; D011985:Receptors, Serotonin; D012261:Ribonucleoproteins; D000099207:SS-A Antigen; C116006:RO60 protein, human