Bonfa E, Viana V S, Barreto A C, Yoshinari N H, Cossermelli W
University of Sao Paulo, Division of Rheumatic Diseases, Brazil.
J Immunol. 1993 May 1;150(9):3917-23.
Sera from 102 patients with chronic Chagas' disease were studied for the presence of autoantibodies to intracellular proteins and nucleic acids by three different methods. Only four sera had autoantibodies detected by indirect immunofluorescence on HEp-2 cells. All of the sera were negative for anti-dsDNA, anti-Ro/SSA, anti-La/SSB, anti-Sm and anti-RNP autoantibodies but 12 (12%) of the sera had low to moderate levels of anti-histone antibodies. When Chagas sera were tested for autoantibodies to a total HeLa cell extract by Western blotting, weak reactivity was observed in 31 sera. Despite significant heterogeneity in the protein Ag targeted by these sera, seven recognized a 23-kDa protein. Strong binding to this 23 kDa protein was observed in one-third of the sera when isolated ribosomes were used as source of Ag. In contrast, no autoreactivity was detected with ribosomal proteins P0, P1, and P2. These findings confirm the presence of autoantibodies in chronic Chagas' disease and indicate a remarkable restricted humoral immune response to human ribosomal proteins. Furthermore, affinity-isolated anti-23-kDa antibody cross-reacted with a Trypanosoma cruzi ribosomal protein of similar molecular weight. This molecular mimicry may be responsible for the apparent breakdown of self-tolerance resulting in tissue damage. Indeed, experiments demonstrating that immunization of mice and rabbit with T. cruzi ribosomes have been reported to induce myocarditis.
采用三种不同方法,对102例慢性恰加斯病患者的血清进行细胞内蛋白质和核酸自身抗体检测。通过间接免疫荧光法检测HEp-2细胞,仅4例血清检测到自身抗体。所有血清抗双链DNA、抗Ro/SSA、抗La/SSB、抗Sm和抗RNP自身抗体均为阴性,但12例(12%)血清有低至中度水平的抗组蛋白抗体。用蛋白质印迹法检测恰加斯病血清对整个HeLa细胞提取物的自身抗体时,31例血清观察到弱反应性。尽管这些血清靶向的蛋白质抗原存在显著异质性,但7例识别出一种23 kDa的蛋白质。以分离的核糖体作为抗原来源时,三分之一的血清观察到与这种23 kDa蛋白质的强结合。相比之下,未检测到与核糖体蛋白P0、P1和P2的自身反应性。这些发现证实慢性恰加斯病存在自身抗体,并表明对人核糖体蛋白的体液免疫反应明显受限。此外,亲和纯化的抗23 kDa抗体与分子量相似的克氏锥虫核糖体蛋白发生交叉反应。这种分子模拟可能是导致自身耐受明显破坏并造成组织损伤的原因。事实上,已有报道称用克氏锥虫核糖体免疫小鼠和兔子可诱发心肌炎。