Characterization of an Immunodominant Antigenic Epitope from Trypanosoma cruzi as a Biomarker of Chronic Chagas' Disease Pathology
Characterization of an Immunodominant Antigenic Epitope from Trypanosoma cruzi as a Biomarker of Chronic Chagas' Disease Pathology
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DOI：
10.1128/cvi.05566-11
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发表时间：
2012-02-01
影响因子：
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通讯作者：
Carlos Lopez, Manuel
中科院分区：
文献类型：
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作者：
Carmen Thomas, M.;Fernandez-Villegas, Ana;Carlos Lopez, Manuel
如今，可用于慢性恰加斯病诊断的技术非常敏感；然而，它们不允许区分患者的临床疾病阶段。本论文描述了克氏锥虫TCCA-2膜蛋白(3972-FGQAAAGDKPPP、6303-FGQAAAGDKPAP和3973-FGQ AAAGDKPSL)中包含的5个不同重复序列中的3个能被慢性恰加斯病患者的血清识别，敏感度高(90%)，而急性期患者的血清不能识别它们。共检测133份失调症患者和50份健康献血员的血清标本。此外，还包括15例不同自身免疫性疾病患者的血清、43例查加斯病以外的感染性疾病患者的血清和38例非查格斯病患者的血清。残基3973肽显示出98%的特异性，因为它不能被有自身免疫性和炎症过程的人识别，也不能被非心肌病患者识别。值得注意的是，查加斯病患者在有症状的慢性期患者的血清中检测到的针对3973表位的抗体水平，涉及心脏或消化系统的变化，高于该病未定期患者的血清检测到的抗体水平。建议所描述的诊断技术也可以用来指示病理程度。氨基酸F、Q和DKP分别位于多肽的第1、3和8到10位，是符合免疫优势抗原表位所必需的。
Nowadays, the techniques available for chronic Chagas' disease diagnosis are very sensitive; however, they do not allow discrimination of the patient's clinical stages of the disease. The present paper describes that three out of the five different repeats contained in the Trypanosoma cruzi TcCA-2 membrane protein (3972-FGQAAAGDKPPP, 6303-FGQAAAGDKPAP, and 3973-FGQ AAAGDKPSL) are recognized with high sensitivity (>90%) by sera from chronic Chagas' disease patients and that they are not recognized by sera from patients in the acute phase of the disease. A total of 133 serum samples from chagasic patients and 50 serum samples from healthy donors were tested. In addition, sera from 15 patients with different autoimmune diseases, 43 serum samples from patients suffering an infectious disease other than Chagas' disease, and 38 serum samples from patients with nonchagasic cardiac disorders were also included in this study. The residue 3973 peptide shows a specificity of >98%, as it is not recognized by individuals with autoimmune and inflammatory processes or by patients with a nonchagasic cardiomyopathy. Remarkably, the levels of antibody against the 3973 epitope detected by the sera from Chagas' disease patients in the symptomatic chronic phase, involving cardiac or digestive alterations, are higher than those detected by the sera from Chagas' disease patients in the indeterminate phase of the disease. It is suggested that the diagnostic technique described could also be used to indicate the degree of pathology. The amino acids F, Q, and DKP located in the peptide at positions 1, 3, and 8 to 10, respectively, are essential to conform to the immunodominant antigenic epitope.