Yamakawa K, Fukuta S, Yoshinaga T, Umemoto S, Itagaki T, Kusukawa R
Department of Internal Medicine, Yamaguchi University School of Medicine, Ube, Japan.
Jpn Circ J. 1987 Jun;51(6):665-75. doi: 10.1253/jcj.51.665.
To determine the immune disturbances involved in the pathogenesis of dilated cardiomyopathy (DCM), the conditions in humoral and cellular immunity of DCM patients were studied. To examine the status in humoral immunity in DCM patients, circulating anti-heart antibodies (AHAbs) were analyzed. Circulating-AHAbs were classified into 4 types "heterophile-like", "intracellular", "intercalated disc" and "nuclear" patterns by indirect immunofluorescence technique, and a high rate of heterophile-like antibody was found in DCM. The cytotoxicity of this antibody was examined in cultured myocardial cells using the two-step method of the complement dependent cytotoxic test. The mean cytotoxic index (CI) value of the heterophile-like antibody positive sera was 22.3, which showed an apparent cytotoxicity against the cultured cells and it may be complement dependent. In addition, the frequency of lymphocyte subsets using monoclonal antibodies (OKT4, OKT8, Leu7, Leu11) and natural killer (NK) activity were evaluated to determine whether DCM patients had an imbalance in cellular immune reactions, which support the hypothesis of an immune disturbance as the pathological mechanism of DCM. The peripheral lymphocyte counts were significantly lower in patients with DCM (1737 +/- 874/mm3) than in normal controls (NC, 2088 +/- 556/mm3) and in patients with ischemic heart diseases (IHD, 2395 +/- 469/mm3, both p less than 0.01). The percentage of T, B, OKT4 and OKT8 positive cells was not statistically different among DCM, IHD, and NC groups, whereas the percentage of T gamma cells was significantly reduced in DCM patients (6.5 +/- 5.0%, p less than 0.05). NK functional activity as tested in DCM patients was frequently deficient (24.1 +/- 16.7% in DCM, 36.7 +/- 12.2% in NC). After 4-hr incubation with recombinant interleukin2 (rIL2), rIL2 induced the enhancement of NK activity in 3 out of 4 DCM patients with low NK activity, although, there was a non-responder to rIL2 in this group. These results suggested that DCM patients have a low IL2 production and/or less numbers of mature cells with NK cell function. Therefore, an imbalance in humoral and cellular immune reactions may cause insidious myocardial damage and subsequently lead to development of DCM.
为了确定扩张型心肌病（DCM）发病机制中涉及的免疫紊乱情况，对DCM患者的体液免疫和细胞免疫状况进行了研究。为检测DCM患者的体液免疫状态，分析了循环抗心脏抗体（AHAbs）。通过间接免疫荧光技术将循环AHAbs分为4种类型：“嗜异性样”、“细胞内”、“闰盘”和“核”型，发现DCM患者中嗜异性样抗体的比例较高。采用补体依赖细胞毒性试验的两步法，在培养的心肌细胞中检测了该抗体的细胞毒性。嗜异性样抗体阳性血清的平均细胞毒性指数（CI）值为22.3，对培养细胞显示出明显的细胞毒性，且可能依赖补体。此外，使用单克隆抗体（OKT4、OKT8、Leu7、Leu11）评估淋巴细胞亚群的频率和自然杀伤（NK）活性，以确定DCM患者是否存在细胞免疫反应失衡，这支持了免疫紊乱作为DCM病理机制的假说。DCM患者的外周淋巴细胞计数（1737±874/mm³）显著低于正常对照组（NC，2088±556/mm³）和缺血性心脏病（IHD）患者（2395±469/mm³，P均＜0.01）。DCM组、IHD组和NC组之间T、B、OKT4和OKT8阳性细胞的百分比无统计学差异，而DCM患者的Tγ细胞百分比显著降低（6.5±5.0%，P＜0.05）。检测发现DCM患者的NK功能活性常存在缺陷（DCM组为24.1±16.7%，NC组为36.7±12.2%）。4例NK活性低的DCM患者中有3例在与重组白细胞介素2（rIL2）孵育4小时后，rIL2诱导NK活性增强，尽管该组中有1例对rIL2无反应。这些结果提示，DCM患者IL2产生减少和/或具有NK细胞功能的成熟细胞数量减少。因此，体液免疫和细胞免疫反应失衡可能导致隐匿性心肌损伤，进而导致DCM的发生。
