Avila J L
Instituto de Biomedicina, Caracas, Venezuela.
Acta Cient Venez. 1992;43(6):330-40.
Increasing evidence suggests that in Chagas' disease chronic-phase pathology is autoimmune in nature. There are at least two nonexclusive explanations for the generation of autoimmunity in Chagas disease: a) infection with the parasite perturbs immunoregulation, leading to loss of tolerance for self-antigens; b) immune recognition of T. cruzi antigens is crossreactive with selected mammalian antigens, leading to autoimmunity (molecular mimicry). Through this latter mechanism, T. cruzi antigens that share epitopes with mammalian nervous tissue may drive autoreactive B- or T-cell clones to expand and cause autoimmune lesions in chronic chagasic patients. Several different antigens sharing this characteristic have been studied, as for example the 160-kDa flagellum-associated surface protein (Fl-160), which has a nervous tissue crossreactive epitope composed by twelve amino acids. Additionally, it has been demonstrated that a trypomastigote stage-specific 85kDa surface glycoprotein (Gp85) has terminal galactosyl(alpha 1-3)galactose terminal residues, which are reactive with chronic chagasic sera. Common glycolipid antigens have also been reported, as for example galactocerebroside, sulfogalactocerebroside and sulfoglucuronylcerebroside, all of them specifically present at high concentrations in mammalian nervous system and in T. cruzi trypomastigotes. Chronic chagasic patients produce elevated levels of antibodies against these three glycolipid antigens. They also do against terminal galactosyl(alpha 1-3)galactose residues present on several acid and neutral glycolipids common either to nervous system or parasite. These antibodies are powerful lytic for circulating T. cruzi trypomastigotes. Another common strongly immunogenic residues are galactosyl(alpha 1-2)galactose, galactosyl(alpha 1-6)galactose and galactofuranosyl(beta 1-3)mannose residues present on several glycoinositolphospholipids (GIPL), against which chronic chagasic patients have elevated levels of specific antibodies. In brief, very specific host-parasite relationships existing only in Chagas' disease may explain the particular peripheral nervous tissue damage seen in acute or chronic stages of this disease. This specificity could depend either on invasion of autonomic ganglia by T. cruzi trypomastigotes and modification of nervous cell surface structures by some of the several mechanisms of acquired molecular mimicry.
越来越多的证据表明，恰加斯病慢性期的病理本质上是自身免疫性的。对于恰加斯病自身免疫的产生，至少有两种并非相互排斥的解释：a）寄生虫感染扰乱免疫调节，导致对自身抗原的耐受性丧失；b）克氏锥虫抗原的免疫识别与特定哺乳动物抗原发生交叉反应，从而导致自身免疫（分子模拟）。通过后一种机制，与哺乳动物神经组织共享表位的克氏锥虫抗原可能会促使自身反应性B细胞或T细胞克隆扩增，并在慢性恰加斯病患者中引发自身免疫性病变。已经研究了几种具有这种特征的不同抗原，例如160 kDa鞭毛相关表面蛋白（Fl-160），它具有由十二个氨基酸组成的神经组织交叉反应表位。此外，已经证明，一种锥鞭毛体阶段特异性85 kDa表面糖蛋白（Gp85）具有末端半乳糖基（α1-3）半乳糖末端残基，这些残基与慢性恰加斯病血清发生反应。也有报道称存在常见的糖脂抗原，例如半乳糖脑苷脂、硫酸半乳糖脑苷脂和硫酸葡萄糖醛酸脑苷脂，它们都以高浓度特异性存在于哺乳动物神经系统和克氏锥虫锥鞭毛体中。慢性恰加斯病患者针对这三种糖脂抗原产生的抗体水平升高。他们针对存在于神经系统或寄生虫共有的几种酸性和中性糖脂上的末端半乳糖基（α1-3）半乳糖残基也会产生抗体。这些抗体对循环中的克氏锥虫锥鞭毛体具有强大的裂解作用。另一种常见的强免疫原性残基是存在于几种糖基肌醇磷脂（GIPL）上的半乳糖基（α1-2）半乳糖、半乳糖基（α1-6）半乳糖和半乳呋喃糖基（β1-3）甘露糖残基，慢性恰加斯病患者针对这些残基的特异性抗体水平升高。简而言之，仅存在于恰加斯病中的非常特殊的宿主-寄生虫关系可能解释了在该疾病急性或慢性阶段所见的特定外周神经组织损伤。这种特异性可能取决于克氏锥虫锥鞭毛体对自主神经节的侵袭以及通过几种获得性分子模拟机制中的某些机制对神经细胞表面结构的修饰。
