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人类恶性黑色素瘤和血液系统肿瘤中循环免疫复合物的生化分类

Biochemical classification of circulating immune complexes in human malignant melanoma and hematologic neoplasms.

作者信息

Queen W D, Bharwani N, Phillips E A, Ruether B A, Phillips T M, Jerry L M

机构信息

Immunochemistry Laboratory, George Washington University Medical Center, Washington, D.C.

出版信息

Oncology. 1989;46(1):14-25. doi: 10.1159/000226674.

DOI:10.1159/000226674
PMID:2915889
Abstract

Circulating immune complexes (CIC) in human cancer are known to be very heterogeneous in size and composition. In 95 staged malignant melanoma patients and 71 individuals with leukemia and lymphoma, this heterogeneity was analyzed biochemically in sera positive for CIC. CICs were measured by a multiassay system and individual complexes were isolated and analyzed by immunological and biochemical methods. Analyses of sera from 100 normal individuals, from 25 rheumatoid women, and a group of 12 laboratory staff who work with human melanoma were included for comparison. Three basic patterns of complexes were identified circulating in the sera of the cancer patients. Type I are medium-sized (17-23S), complement-fixing complexes usually occurring in combinations. The prototype in melanoma contained IgG antibody and additional glycoprotein components and bound complement by the classical pathway. In hematological malignancies four subtypes could be identified depending on whether the antibody class was IgG or IgM, the nonimmunoglobulin component was glycoprotein or protein, and whether complement fixation occurred by the classical or alternate pathway. Type II complexes were noncomplement-fixing, medium-sized complexes (15-21S), which in melanoma contained IgG antibody and additional protein components. In the hematologic malignancies two subtypes could be identified depending on whether the antibody class was IgG or IgM. Both subtypes contained a glycoprotein nonimmunoglobulin component. Both melanoma and hematologic tumors had type III heavy complexes (36-44S) which were noncomplement-fixing and contained only immunoglobulin components, either IgG-IgG or IgM-IgG. As expected the rheumatoid arthritis patients frequently had both 7S and 21-23S CICs containing IgG as well as IgM rheumatoid factor with complement fixation via the classical pathway. No CICs were detected in normal young men and women (20-30 years); a few individuals in middle age (31-50 years) had small (7-11S) CICs which bound complement by the classical pathway and contained IgG and a protein nonimmunoglobulin component. The frequency of these 7S complexes increased with advancing age, with the appearance of 23S IgG-IgG or IgM-IgG complexes. IgG antibodies from only the melanoma patients reacted with cytoplasmic components of fresh melanoma cells, except the laboratory workers where all of their isolated CIC antibodies also reacted with melanoma cells. Thus the heterogeneity of complexes in melanoma is not random, but can be classified into three basic biochemical patterns. The hematologic group provides a slightly richer variation of subtypes within this basic scheme.

摘要

已知人类癌症中的循环免疫复合物(CIC)在大小和组成上具有很大的异质性。在95例分期恶性黑色素瘤患者以及71例白血病和淋巴瘤患者中,对CIC呈阳性的血清进行了生化分析,以研究这种异质性。通过多检测系统测量CIC,并通过免疫学和生化方法分离和分析单个复合物。还纳入了100名正常个体、25名类风湿性关节炎女性患者以及一组12名从事人类黑色素瘤研究的实验室工作人员的血清进行比较。在癌症患者的血清中鉴定出三种基本的复合物模式。I型是中等大小(17 - 23S)、可固定补体的复合物,通常以组合形式出现。黑色素瘤中的原型复合物含有IgG抗体和其他糖蛋白成分,并通过经典途径结合补体。在血液系统恶性肿瘤中,根据抗体类别是IgG还是IgM、非免疫球蛋白成分是糖蛋白还是蛋白质以及补体固定是通过经典途径还是替代途径,可鉴定出四种亚型。II型复合物是不可固定补体的中等大小复合物(15 - 21S),在黑色素瘤中含有IgG抗体和其他蛋白质成分。在血液系统恶性肿瘤中,根据抗体类别是IgG还是IgM可鉴定出两种亚型。两种亚型都含有一种糖蛋白非免疫球蛋白成分。黑色素瘤和血液系统肿瘤都有III型重复合物(36 - 44S),它们不可固定补体,仅含有免疫球蛋白成分,即IgG - IgG或IgM - IgG。正如预期的那样,类风湿性关节炎患者经常有7S和21 - 23S的CIC,含有IgG以及IgM类风湿因子,并通过经典途径固定补体。在正常年轻男性和女性(20 - 30岁)中未检测到CIC;中年(31 - 50岁)的一些个体有小的(7 - 11S)CIC,它们通过经典途径结合补体,含有IgG和一种蛋白质非免疫球蛋白成分。随着年龄的增长,这些7S复合物的频率增加,并出现23S的IgG - IgG或IgM - IgG复合物。仅黑色素瘤患者的IgG抗体与新鲜黑色素瘤细胞的细胞质成分发生反应,而实验室工作人员分离出的所有CIC抗体也与黑色素瘤细胞发生反应。因此,黑色素瘤中复合物的异质性并非随机的,而是可以分为三种基本的生化模式。血液系统肿瘤组在这个基本模式内提供了稍微更丰富的亚型变化。

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