Laboratory of Immunology, Universidade Federal do Triângulo Mineiro, Uberaba, Minas Gerais, Brazil.
J Interferon Cytokine Res. 2013 Mar;33(3):130-5. doi: 10.1089/jir.2012.0024. Epub 2013 Jan 4.
Lymphotoxin-alpha (LT-alpha or LTA) is an inflammatory cytokine that is involved in the organization and maintenance of the inflammatory process and in the arrangement of cells at the site of inflammation. These features suggest an important role in the development of chronic Chagas' disease, especially the cardiac form. The objective of this study was to evaluate LT-alpha genetics and its biological role in chronic Chagas' disease. A total of 284 subjects were studied. The LT-alpha single-nucleotide polymorphism (+252) was analyzed by the polymerase chain reaction-restriction fragment length polymorphism and expression by enzyme-linked immunosorbent assay in culture supernatants and in individual T lymphocytes by flow cytometry. The risk of developing the cardiac form was 2.8 times higher among carriers of genotype GG and 2.4 times among carriers of genotype GA when compared to subjects carrying genotype AA. Seropositive subjects carrying the G allele produced significantly higher levels of LT-alpha. The cytokine was mainly expressed by CD8(+) T lymphocytes in the absence of any stimulus and after stimulation with the Trypanosoma cruzi antigen. This study provides genetic and biological evidence for an important role of LT-alpha in the development of the cardiac form of Chagas' disease.
淋巴毒素-α（LT-α 或 LTA）是一种炎症细胞因子，参与炎症过程的组织和维持，以及炎症部位细胞的排列。这些特征表明其在慢性恰加斯病（特别是心脏形式）的发展中具有重要作用。本研究旨在评估 LT-α 的遗传学及其在慢性恰加斯病中的生物学作用。共研究了 284 名受试者。通过聚合酶链反应-限制性片段长度多态性分析 LT-α 单核苷酸多态性（+252），并通过酶联免疫吸附试验和流式细胞术在培养上清液和个体 T 淋巴细胞中检测其表达。与携带 AA 基因型的受试者相比，携带 GG 基因型的受试者发生心脏形式的风险高 2.8 倍，携带 GA 基因型的受试者发生心脏形式的风险高 2.4 倍。携带 G 等位基因的血清阳性受试者产生的 LT-α 水平显著更高。该细胞因子在没有任何刺激物的情况下主要由 CD8+T 淋巴细胞表达，并在刺激克氏锥虫抗原后表达。本研究为 LT-α 在恰加斯病心脏形式的发展中具有重要作用提供了遗传和生物学证据。
