Anti-SSA/Ro52 autoantibodies blocking the cardiac 5-HT4serotoninergic receptor could explain neonatal lupus congenital heart block

Pierre Eftekhari (1) , Laurent Sallé (2) , Frank Lezoualc'H (3) , Jeanne Mialet (3) , Monique Gastineau (3) , Jean-Paul Briand (1) , David a. Isenberg (4) , Gilbert j. Fournié , Jorge Argibay (2) , Rodolphe Fischmeister (3) , Sylviane Muller (1) , Johan Hoebeke (1)

1 ICT - Immunologie et chimie thérapeutiques
2 IPBC - Laboratoire de Physiologie des Cellules Cardiaques et Vasculaires
3 Cardiologie cellulaire et moléculaire
4 UCL - University College of London [London]

The 52-kDa SSA/Ro (Ro52) ribonucleoprotein is an antigenic target strongly associated with the autoimmune response in mothers whose children develop neonatal lupus and congenital heart block. When sera from patients with systemic lupus erythematosus were used as autoimmune controls in an enzyme immunoassay to screen for antibodies against the human serotoninergic 5-HT 4-receptor, a high correlation was found between the presence of anti-Ro52 protein antibodies in such sera and antibodies reacting with a synthetic peptide, corresponding to the second extracellular loop of the human 5-HT 4 receptor (amino acid residues 165-185). Homology scanning between the 5-HT 4 peptide and the sequence of the Ro52 protein indicated two potential common epitopes located between residues 365 and 396 of the Ro52 protein. Cross-reactivity was found between the peptide derived from the 5-HT 4 receptor, and a peptide corresponding to residues 365-382 of the Ro52 protein. Autoantibodies, affinity-purified on the 5-HT 4 receptor peptide, specifically recognized both the Ro52 protein and the 5-HT 4 receptor protein in immunoblots. The affinity-purified antibodies antagonized the serotonin-induced L-type Ca channel activation on human atrial cells. This effect could explain the electrophysiological abnormalities in neonatal lupus.

Mots clés: Neonatal lupus; Congenital heart block; SSA; Ro52; 5-HT 4 serotonin receptor; Cross-reactivity

Domaines: Rhumatologie et système ostéo-articulaire

Pierre Eftekhari, Laurent Sallé, Frank Lezoualc'H, Jeanne Mialet, Monique Gastineau, et al.. Anti-SSA/Ro52 autoantibodies blocking the cardiac 5-HT4serotoninergic receptor could explain neonatal lupus congenital heart block. European Journal of Immunology, 2000, 30 (10), pp.2782-2790. ⟨10.1002/1521-4141(200010)30:10<2782::AID-IMMU2782>3.0.CO;2-9⟩. ⟨hal-03611686⟩