Anti idiotypic recognition of auto and allo antibodies to factor VIII by immunoglobulin preparations from single blood donors and large plasma pool.

Y Sultan, F Rossi, M Kazatchkine
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Abstract

Therapeutic immunoglobulins from commercial origin were administered to patients with allo and auto antibodies to factor VIII. The protocol used was similar to the prescription suggested for ITP, 0.4 g/kg body weight for five consecutive days. In patients with auto antibodies two kinds of effects were observed: A direct interaction between IVIg and the factor VIII inhibitor and long term interaction on antibody synthesis. The direct interaction observed in vivo was demonstrated to be mediated through Fab'2 fragments of both idiotypic interaction. This was also demonstrated using binding experiments and affinity chromatography experiments: Fab'2 fragments of IVIg were coupled to sepharose and Fab'2 fragments of patients IgG with allo and auto antibodies to Factor VIII were circulated through the column. The recovery of anti Factor VIII antibodies after elution was possible in 2 cases of allo antibodies out of 3 tested and 3 cases of auto antibodies out of 4. The question of anti idiotypes against factor VIII inhibitors in single individuals was investigated. IgG and Fab'2 fragments from single blood donors were isolated and tested for their inhibitory capacity against Fab'2 fragments of three different auto antibodies. The results did not show statistical differences between males and females however in the group of male blood donors, aging was a positive parameter for the presence of anti idiotypic antibodies against factor VIII inhibitors. Anti idiotypic antibodies against factor VIII inhibitors were present in 17.2% of the blood donor tested.

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单个献血者和大血浆池的免疫球蛋白制剂对因子VIII自身抗体和容体抗体的抗独特型识别。
来自商业来源的治疗性免疫球蛋白被给予具有同种异体和自身因子VIII抗体的患者。使用的方案与ITP的建议处方相似,0.4 g/kg体重,连续5天。在自身抗体患者中观察到两种作用:IVIg与因子VIII抑制剂之间的直接相互作用和对抗体合成的长期相互作用。在体内观察到的直接相互作用被证明是通过独特型相互作用的Fab'2片段介导的。结合实验和亲和层析实验也证明了这一点:IVIg的Fab'2片段与sepharose偶联,患者IgG的Fab'2片段与因子VIII的alloo抗体和自身抗体通过柱循环。3例同种异体抗体和4例自体抗体洗脱后分别有2例和3例可回收抗VIII因子抗体。对单个个体抗因子VIII抑制剂独特型的问题进行了研究。从单个献血者中分离IgG和Fab'2片段,检测其对三种不同自身抗体Fab'2片段的抑制能力。结果没有显示男性和女性之间的统计差异,但在男性献血者组中,年龄是针对因子VIII抑制剂的抗独特型抗体存在的积极参数。17.2%的供血者检测到抗因子VIII抑制剂的独特型抗体。
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