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DETECTION OF PATIENTS AT RISK FOR DEVELOPING INTEGRIN ANTAGONIST/ AGONIST MEDIATED DISEASE STATES

机译:发展为整合拮抗剂/激动剂介导的疾病状态的危险患者检测

摘要

This invention relates to the detection of patients at risk for developing integrin antagonist/agonist mediated disease states. This invention relates to assays useful for the detection in a patient bodily fluid sample of drug-dependent antibodies which bind to integrins, or intergrin-associated proteins or complexes thereof in the presence of an integrin antagonist/agonist. This invention also relates to assays useful for the detection in a patient bodily fluid sample of drug-dependent antibodies (DDABS) that bind to integrins, including the platelet glycoprotein IIb/IIIa (GPIIb/IIIa), in the presence of a integrin agonist and/or antagonist. This invention also relates to procedures for identifying integrin antagonists/agonists that are less prone to elicit integrin antagonist/agonist mediated disease states. ;This invention also relates to procedures which increase the recovery of integrin-directed antibodies in body fluids, resulting in an increased sensitivity and specificity of DDAB detection assays. This invention also relates to procedures for treating blood samples, which dissociate antibodies to GPIIb/IIIa from the platelet surface, thereby increasing the recovery from the platelet supernatant. This invention also relates to the use of different GPIIb/IIIa preparations to identify patients at risk for early-onset thrombocytopenia upon treatment with GPIIb/IIIa antagonist/agonists, thereby increasing the specificity of antibody detection. ;This invention also relates to the use of DDABs as a positive control and calibration standard for DDAB assays. ;Such methods, procedures and assays are useful for identifying patients who may be at risk to develop disease states mediated by treatment with integrin antagonists/agonists.
机译:本发明涉及对处于发展整联蛋白拮抗剂/激动剂介导的疾病状态的风险的患者的检测。本发明涉及可用于在患者体液样品中检测在整联蛋白拮抗剂/激动剂存在下与整联蛋白或与整联蛋白相关的蛋白或其复合物结合的药物依赖性抗体的测定法。本发明还涉及可用于在患者体液样品中检测在整联蛋白激动剂和肽存在下结合至整联蛋白的药物依赖性抗体(DDABS)的方法,所述整联蛋白包括血小板糖蛋白IIb / IIIa(GPIIb / IIIa)。 /或拮抗剂。本发明还涉及鉴定不太容易引起整联蛋白拮抗剂/激动剂介导的疾病状态的整联蛋白拮抗剂/激动剂的方法。本发明还涉及增加体液中整联蛋白定向抗体的回收率,从而导致DDAB检测测定法的灵敏度和特异性提高的方法。本发明还涉及用于处理血液样品的方法,该方法从血小板表面解离针对GPIIb / IIIa的抗体,从而增加从血小板上清液的回收率。本发明还涉及使用不同的GPIIb / IIIa制剂来鉴定在用GPIIb / IIIa拮抗剂/激动剂治疗后有发生早期血小板减少症风险的患者的用途,从而增加抗体检测的特异性。本发明还涉及使用DDAB作为DDAB测定的阳性对照和校准标准。 ;这些方法,程序和测定法可用于识别可能面临通过整联蛋白拮抗剂/激动剂治疗介导的疾病状态风险的患者。

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