Pathophysiological significance of autoantibody to liver plasma membrane-bound cytoskeleton-related proteins in liver diseases.

在本研究中，我们发现了从未被描述过的钙调素（calmodulin, CaM）自身抗体，并着重阐明了该自身抗体的临床和病理生理意义。采用酶联免疫吸附试验（ELISA）检测CaM自身抗体（CaM antibody）。用酶标抗人IgG、IgM和IgA检测牛脑CaM与免疫板结合的免疫球蛋白。牛脑CaM或人红细胞CaM可通过吸收血清来降低CaM抗体，而肌动蛋白、肌钙蛋白C或DNA则不能。免疫印迹法证实了CaM抗体的存在。慢性肝病和胶原病患者血清中均检测到IgG类抗体，而慢性肝病患者血清中检测到IgM类抗体的频率高于胶原病患者，在部分血清样品中，游离Ca^<++>存在时抗体滴度高于游离Ca^<++>存在时抗体滴度，提示它们识别了CaM的构象。利用CaM偶联琼脂糖柱，我们发现有三种类型的抗体：结合Ca^<++>的CaM抗体，不结合Ca^<++>的CaM抗体和两者兼而有之。CaM抗体抑制磷酸二酯酶活性。但CaM抗体是否参与肝细胞损伤还有待进一步研究。

In this study, we found the autoantibody to calmodulin (CaM) which had never been described, and concentrated on clarification of clinical and pathophysiological significance of this autoantibody. The autoantibody to CaM (CaM antibody) was assayed by enzyme-linked immunosorbent assay (ELISA). Immunoglobulin bound to bovine brain CaM fixed to immunoplate was determined using HRP-conjugated antihuman IgG, IgM ad IgA. CaM antibody was decreased by absorption of serum with bovine brain CaM or human erythrocyte CaM, not with actin, tropnin C or DNA. The presence of CaM antiobody was also confirmed by immunoblotting method. IgG class antibody was found in the sera from the patients with collagen diseases as well as those with chronic liver diseases, whereas IgM class antiobody was detected more frequently in the pationts with chronic liver diseases than in those with collagen diseases, In some serum samples, the antibody titres were higher in the presence of free Ca^<++> than in its absence, suggesting that they recognized conformations of CaM. Using CaM-conjugated agarose column, we found that there were three types of antibody : antibodies that bound to Ca^<++>-bound CaM, Ca^<++>-free CaM and both of these. CaM antiobody inhibited phosphodiesterase activity. However it remained for future study whether CaM antibody was involved in the liver cell injury or not.