AUTOANTIBODIES IN WOMEN WITH SILICONE BREAST IMPLANTS

硅胶乳房植入物女性体内的自身抗体

• 批准号: 3149489
• 负责人: Eng M TAN
• 金额: $ 18.71万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-01 至 1996-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3149489
• 关键词: antibody specificity; antigens; antinuclear autoantibody; autoimmune disorder; biomaterial compatibility; chronic fatigue syndrome; enzyme linked immunosorbent assay; female; fibromyalgia; genetic library; human genetic material tag; human subject; immunofluorescence technique; immunoprecipitation; mammary gland; molecular cloning; recombinant proteins; scleroderma; silicone rubber; systemic lupus erythematosus; western blottings

Certain "autoimmune" diseases are observed in women who have undergone breast augmentation procedures with encapsulated silicone gel implants. It has, however, not been determined whether this is a cause and effect relationship or whether the auto immune diseases are found in normally expected incidence and prevalence as in the general population. Our own initial studies have shown that antinuclear antibodies are present in up to 90% of women with silicone breast implants who have defined auto immune diseases and that some of the autoantibodies are those which have been recognized in idiopathic forms of scleroderma and lupus while many others remain unidentified. The objective of this proposal is to comprehensively characterize the profiles and fine specificities of autoantibodies in the sera of patients with silicone breast implants. This will be done with techniques which include immunofluorescence microscopy, Western blotting and immunoprecipitation of biosynthetically labelled cells by which antigenic proteins and/or their associated RNAs can be detected. It has already been shown that there are some new antigens reacting with antibodies from patients with silicone breast implants. A number of sera which recognize unknown antigens will be selected as cloning reagents to probe cDNA expression libraries. Analysis of the nucleic acid and protein sequences of the isolated antigens will be used to determine if characteristic structural and functional motifs are present in these antigens since this information might provide leads to their nature. Recombinant antigens will be generated from the cDNA clones and the authenticity of the recombinant proteins verified in ELISA with the original sera used for library screening. It will then be possible with ELISA and screening of large numbers of sera to ascertain whether autoantibodies to these antigens are unique for silicone-associated auto immune diseases or are also present in the idiopathic diseases. If autoantibody profiles and fine specificities are not different from spontaneous autoimmune diseases, the evidence would favor an adjuvant-like effect of silicone in the promotion of what has been called idiopathic autoimmune disease. However, if the profiles and specificities show that although there are certain similarities as has been reported, there are also distinct differences, the evidence would argue that silicone was provoking autoimmune syndromes by additionally different mechanisms from the idiopathic forms of these diseases.

某些“自身免疫性”疾病在经历过 隆胸手术与封装硅凝胶植入物。 然而，还没有确定这是否是因果关系。 关系或自身免疫性疾病是否在正常 与一般人群中的预期发病率和患病率相同。 我们自己 最初的研究表明，抗核抗体存在于 90%的硅胶乳房植入体女性， 疾病和一些自身抗体是那些已经被 在硬皮病和狼疮的特发性形式中被认识到，而许多其他 仍然身份不明 本提案的目的是全面描述 患者血清中自身抗体的谱和精细特异性 硅胶隆胸 这将通过以下技术来完成， 包括免疫荧光显微术、蛋白质印迹法 生物合成标记细胞的免疫沉淀， 可以检测蛋白质和/或其相关的RNA。 它已经 已经表明，有一些新的抗原与来自 硅胶乳房植入体的患者。 一些血清可以识别 选择未知抗原作为克隆试剂， 表达式库。核酸和蛋白质序列分析 分离的抗原将用于确定是否具有特征性 结构和功能基序存在于这些抗原中， 信息可能会提供线索，他们的性质。 重组抗原 将产生的cDNA克隆和真实性的 使用用于检测的原始血清在ELISA中验证重组蛋白 文库筛选 然后将有可能通过ELISA和筛选 大量的血清，以确定是否自身抗体，这些 抗原对于硅酮相关的自身免疫性疾病是独特的， 也存在于特发性疾病中。 如果自身抗体谱和精细特异性与 自发性自身免疫性疾病，证据将有利于 硅胶在促进所谓的特发性 自身免疫性疾病 但是，如果特征和特异性表明， 虽然有某些相似之处，如已报告的， 也有明显的差异，证据表明，硅胶是 引发自身免疫综合征的另外不同的机制， 这些疾病的特发性形式