Instituto Nacional de Parasitología Dr Mario Fatala Chaben, ANLIS-Malbrán, Ministerio de Salud de la Nación, Buenos Aires, Argentina.
Parasite Immunol. 2012 Nov;34(11):499-510. doi: 10.1111/j.1365-3024.2012.01378.x.
Sulphoglycosphingolipids, present on the surface of diverse cells, participate in the regulation of various cellular events. However, little is known about the structure and the role of sulphoglycosphingolipids in trypanosomatids. Herein, sulphated dihexosylceramide structures - composed mainly of sphingosine as the long chain base acylated with stearic acid - have been determined for the first time in Trypanosoma cruzi epimastigotes by UV-MALDI-TOF-MS analysis. Interestingly, inhibition ELISA assays using cruzipain as antigen and polyclonal rabbit antibodies specific for cruzipain, the major cysteine proteinase of T. cruzi, or for its C-terminal domain, have demonstrated (i) that sulphate epitopes are shared between cruzipain and sulphatides of T. cruzi, (ii) that cross-reactivity maps to the C-terminal domain and (iii) the existence of other antigenic determinants in the glycolipidic structures. These features provide evidence that sulphate groups are antigenic in sulphate-containing parasite glycoconjugates. Furthermore, IgG2 antibody levels inversely correlate with disease severity in chronic Chagas disease patients, suggesting that IgG2 antibodies specific for sulphated epitopes might be associated with protective immunity and might be considered as potential surrogates of the course of chronic Chagas disease.
硫酸神经酰胺糖脂存在于各种细胞表面，参与多种细胞事件的调节。然而，人们对糖脂在原生动物中的结构和功能知之甚少。本文首次通过 UV-MALDI-TOF-MS 分析，确定了在 Trypanosoma cruzi 无鞭毛体中主要由长链碱基神经酰胺酰化的硬脂酸组成的硫酸二己糖神经酰胺结构。有趣的是，使用克氏锥虫作为抗原的抑制 ELISA 检测和针对克氏锥虫主要半胱氨酸蛋白酶或其 C 末端结构域的多克隆兔抗体特异性进行的检测表明：(i) 硫酸盐表位在克氏锥虫和克氏锥虫的硫酸神经酰胺之间共享；(ii) 交叉反应性映射到 C 末端结构域；(iii) 在糖脂结构中存在其他抗原决定簇。这些特征表明硫酸盐基团在含硫酸盐的寄生虫糖缀合物中是抗原性的。此外，慢性恰加斯病患者的 IgG2 抗体水平与疾病严重程度呈负相关，这表明针对硫酸化表位的 IgG2 抗体可能与保护性免疫有关，并可能被视为慢性恰加斯病病程的潜在替代标志物。
