Eftekhari P, Sallé L, Lezoualc'h F, Mialet J, Gastineau M, Briand J P, Isenberg D A, Fournié G J, Argibay J, Fischmeister R, Muller S, Hoebeke J
UPR 9021 CNRS "Immunochimie des Peptides et des Virus", Strasbourg, France.
Eur J Immunol. 2000 Oct;30(10):2782-90. doi: 10.1002/1521-4141(200010)30:10<2782::AID-IMMU2782>3.0.CO;2-9.
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-HT4-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-HT4 receptor (amino acid residues 165-185). Homology scanning between the 5-HT4 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-HT4 receptor, and a peptide 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 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.
52-kDa SSA/Ro（Ro52）核糖核蛋白是一种抗原靶点，与孩子患新生儿狼疮和先天性心脏传导阻滞的母亲的自身免疫反应密切相关。在一项酶免疫测定中，当将系统性红斑狼疮患者的血清用作自身免疫对照来筛查抗人血清素能5-HT4受体抗体时，发现此类血清中抗Ro52蛋白抗体的存在与与对应于人5-HT4受体第二个细胞外环（氨基酸残基165 - 185）的合成肽发生反应的抗体之间存在高度相关性。5-HT4肽与Ro52蛋白序列之间的同源性扫描表明，在Ro52蛋白的365至396位残基之间存在两个潜在的共同表位。在源自5-HT4受体的肽与对应于Ro52蛋白365 - 382位残基的肽之间发现了交叉反应性。在5-HT4受体肽上亲和纯化的自身抗体在免疫印迹中特异性识别Ro52蛋白和5-HT4受体蛋白。亲和纯化的抗体拮抗血清素诱导的人心房细胞上L型钙通道的激活。这种效应可以解释新生儿狼疮中的电生理异常。
