O'Donoghue H L, Lawson C M, Reed W D
Department of Medicine, University of Western Australia, Nedlands.
Immunology. 1990 Sep;71(1):20-8.
Myocarditis accompanies sublethal mouse cytomegalovirus (MCMV) infection in susceptible BALB/c mice and persists beyond the acute phase of infection, in the absence of demonstrable virus antigen but in the continuing presence of autoantibodies to cardiac muscle. Heart tissue autoantibodies of the IgG class were first detected by ELISA in sera at Days 3-5 post-infection (PI) and persisted to Day 100, in two strains of MCMV-infected mice which are susceptible (BALB/c) and resistant (C57BL/10) to MCMV-induced myocarditis. Analysis by immunoblot showed that autoantibodies in early immune sera (Day 10) from both mouse strains reacted with the contractile proteins troponin, tropomyosin and myosin, as well as with other unidentified polypeptides within normal mouse organ homogenates. However, the dominant reactivity of late immune sera (Day 100) was to a 200,000 molecular weight (MW) polypeptide in muscle homogenates identified as the heavy chain of myosin. Autoantibodies reacting with the cardiac or striated muscle isoforms of myosin were assessed by ELISA in BALB/c and C57BL/10 mice. At Days 28, 56 and 100 PI only the susceptible BALB/c strain had high titres of autoantibodies reacting with the cardiac isoform of myosin. Increasing the virus dose given to C57BL/10 mice resulted in slight increases in titres of anti-myosin antibody; however, the peak antibody titres did not approach those of BALB/c mice and persisting myocarditis did not develop. Absorption experiments showed that cardiac myosin-specific antibodies were present in immune sera from susceptible BALB/c mice at Day 100 but not in resistant C57BL/10 mice by ELISA and immunoblot. These results demonstrate that autoimmunity to myosin is a prominent feature of the humoral autoimmune response following MCMV infection, and that there are differences both in fine isoform specificity and titre of anti-myosin antibodies between strains of mice that develop persisting myocarditis and strains that do not. Cardiac myosin-specific autoantibodies may play an immunopathogenic role in CMV-induced myocarditis.
在易感的BALB/c小鼠中，心肌炎伴随亚致死剂量的小鼠巨细胞病毒（MCMV）感染出现，并在感染急性期过后持续存在，此时虽无明显的病毒抗原，但存在针对心肌的自身抗体。通过酶联免疫吸附测定（ELISA）首次在感染后第3 - 5天（PI）的血清中检测到IgG类心脏组织自身抗体，并在两株感染MCMV的小鼠（对MCMV诱导的心肌炎易感的BALB/c和有抗性的C57BL/10）中持续至第100天。免疫印迹分析表明，两种小鼠品系早期免疫血清（第10天）中的自身抗体与收缩蛋白肌钙蛋白、原肌球蛋白和肌球蛋白反应，也与正常小鼠器官匀浆中的其他未鉴定多肽反应。然而，晚期免疫血清（第100天）的主要反应是针对肌肉匀浆中一种分子量为200,000的多肽，该多肽被鉴定为肌球蛋白重链。通过ELISA在BALB/c和C57BL/10小鼠中评估了与肌球蛋白的心脏或横纹肌异构体反应的自身抗体。在感染后第28、56和100天，只有易感的BALB/c品系具有高滴度的与肌球蛋白心脏异构体反应的自身抗体。给C57BL/10小鼠增加病毒剂量导致抗肌球蛋白抗体滴度略有增加；然而，抗体滴度峰值未达到BALB/c小鼠的水平，且未发生持续性心肌炎。吸收实验表明，通过ELISA和免疫印迹，在第100天易感的BALB/c小鼠免疫血清中存在心肌肌球蛋白特异性抗体，而抗性的C57BL/10小鼠中则没有。这些结果表明，针对肌球蛋白的自身免疫是MCMV感染后体液自身免疫反应的一个突出特征，并且在发生持续性心肌炎的小鼠品系和未发生持续性心肌炎的小鼠品系之间，抗肌球蛋白抗体的精细异构体特异性和滴度均存在差异。心肌肌球蛋白特异性自身抗体可能在CMV诱导的心肌炎中起免疫致病作用。
