Induction of neonatal lupus in pups of mice immunized with synthetic peptides derived from amino acid sequences of the serotoninergic 5-HT 4 receptor

• Published in: European journal of immunology 2001, Vol.31 (2), p.573-579
• Main Authors: Eftekhari, Pierre, Roegel, Jean-Christophe, Lezoualc'H, Frank, Fischmeister, Rodolphe, Imbs, Jean-Louis, Hoebeke, Johan
• Format: Article
• Language: English
• Subjects: Immunology; Life Sciences
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/1521-4141(200102)31:2<573::aid-immu573>3.0.co;2-9

We have previously suggested that the recognition of a cross-reactive epitope on the 5-HT 4 receptor and the 52-kDa SSA/Ro protein by serotonin-antagonizing autoantibodies could explain the electrophysiological symptoms of congenital heart block in neonatal lupus. To confirm this hypothesis, we immunized female mice with four synthetic peptides corresponding to the recognized epitopes. All mice developed anti-peptide antibodies, which cross-reacted with the Ro52 and 5-HT 4 receptor peptides and recognized both cognate proteins. Peptide-immune mice were mated. The pups from mice immunized with the Ro52 peptides had no symptoms of neonatal lupus apart from bradycardia. However, pups from mice immunized with the 5-HT 4 receptor peptides and bradycardia, atrioventricular block of type I or II, longer QT intervals, skin rashes and neuromotoric problems. The 5-HT 4 receptor was detectable in the different fetal tissues affected (heart, skin and brain) by immunohistochemistry. Hearts from diseased pups were less developed and showed disorganized myocardial hyperplasia, compared to the normal littermates. These results demonstrate that the serotoninergic 5-HT 4 receptor is the antigenic target of physiopathological autoantibodies in neonatal lupus.