Kaplan D, Ferrari I, Bergami P L, Mahler E, Levitus G, Chiale P, Hoebeke J, Van Regenmortel M H, Levin M J
Instituto de Investigaciones en Ingenieria Genetica y Biologia Molecular-Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina, Facultad de Ciencias Exactas y Naturales-University of Buenos Aires, Argentina.
Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10301-6. doi: 10.1073/pnas.94.19.10301.
Anti-P antibodies present in sera from patients with chronic Chagas heart disease (cChHD) recognize peptide R13, EEEDDDMGFGLFD, which encompasses the C-terminal region of the Trypanosoma cruzi ribosomal P1 and P2 proteins. This peptide shares homology with the C-terminal region (peptide H13 EESDDDMGFGLFD) of the human ribosomal P proteins, which is in turn the target of anti-P autoantibodies in systemic lupus erythematosus (SLE), and with the acidic epitope, AESDE, of the second extracellular loop of the beta1-adrenergic receptor. Anti-P antibodies from chagasic patients showed a marked preference for recombinant parasite ribosomal P proteins and peptides, whereas anti-P autoantibodies from SLE reacted with human and parasite ribosomal P proteins and peptides to the same extent. A semi-quantitative estimation of the binding of cChHD anti-P antibodies to R13 and H13 using biosensor technology indicated that the average affinity constant was about 5 times higher for R13 than for H13. Competitive enzyme immunoassays demonstrated that cChHD anti-P antibodies bind to the acidic portions of peptide H13, as well as to peptide H26R, encompassing the second extracellular loop of the beta1 adrenoreceptor. Anti-P antibodies isolated from cChHD patients exert a positive chronotropic effect in vitro on cardiomyocytes from neonatal rats, which resembles closely that of anti-beta1 receptor antibodies isolated from the same patient. In contrast, SLE anti-P autoantibodies have no functional effect. Our results suggest that the adrenergic-stimulating activity of anti-P antibodies may be implicated in the induction of functional myocardial impairments observed in cChHD.
慢性恰加斯心脏病（cChHD）患者血清中的抗P抗体可识别肽R13，即EEEDDDMGFGLFD，其包含克氏锥虫核糖体P1和P2蛋白的C末端区域。该肽与人核糖体P蛋白的C末端区域（肽H13，EESDDDMGFGLFD）具有同源性，而后者又是系统性红斑狼疮（SLE）中抗P自身抗体的靶标，并且与β1 - 肾上腺素能受体第二个细胞外环的酸性表位AESDE具有同源性。恰加斯病患者的抗P抗体对重组寄生虫核糖体P蛋白和肽表现出明显的偏好，而SLE患者的抗P自身抗体与人及寄生虫核糖体P蛋白和肽的反应程度相同。使用生物传感器技术对cChHD抗P抗体与R13和H13结合的半定量估计表明，R13的平均亲和常数比H13高约5倍。竞争性酶免疫测定表明，cChHD抗P抗体可与肽H13的酸性部分以及包含β1肾上腺素能受体第二个细胞外环的肽H26R结合。从cChHD患者分离出的抗P抗体在体外对新生大鼠心肌细胞具有正性变时作用，这与从同一患者分离出的抗β1受体抗体的作用非常相似。相比之下，SLE抗P自身抗体没有功能作用。我们的结果表明，抗P抗体的肾上腺素能刺激活性可能与cChHD中观察到的功能性心肌损伤的诱导有关。
