Anti-SSA/Ro52 autoantibodies blocking the cardiac 5-HT4 serotoninergic receptor could explain neonatal lupus congenital heart block

The 52-kDa SSA/Ro (Ro52) ribonucleoprotein is an antigenic target strongly associated with the autoimmune response in mothers whose children develop n eonatal lupus and congenital heart block. When sera from patients with syst emic lupus erythematosus were used as autoimmune controls in an enzyme immu noassay to screen for antibodies against the human serotoninergic 5-HT4-rec eptor, a high correlation was found between the presence of anti-Ro52 prote in antibodies in such sera and antibodies reacting with a synthetic peptide , corresponding to the second extracellular loop of the human 5-HT4 recepto r (amino acid residues 165-185). Homology scanning between the 5-HT4 peptid e and the sequence of the Ro52 protein indicated two potential common epito pes located between residues 365 and 396 of the Ro52 protein. Cross-reactiv ity was found between the peptide derived from the 5-HT4 receptor, and a pe ptide corresponding to residues 365-382 of the Ro52 protein. Autoantibodies , affinity-purified on the 5-HT4 receptor peptide, specifically recognized both the Ro52 protein and the 5-HT4 receptor protein in immunoblots. The af finity-purified antibodies antagonized the serotonin-induced L-type Ca chan nel activation on human atrial cells. This effect could explain the electro physiological abnormalities in neonatal lupus.