a) providing samples of a sufficient number of individuals, in particular at least 10 individuals, the samples containing B- and T-lymphocytes, natural killer cells, invariant T-cells and monocytes of the individuals;b) determination of values of immune parameters which are either static, such as leukocyte subpopulations and cytokine-level in the plasma or functional, like gene expression and cytokine release after lipopolysaccharide (LPS) and/or IVIG stimulation ex vivo;c) the determined values derived from immune parameters of the samples of the individuals are ordered in quartiles and the values belonging to the 1. quartile, values distributed at the low end of the corresponding parameter, are set to “−1”, whereas values distributed in the 4. quartile are set to “+1” for an individual LDA-score calculation and values in between are set to “0”;d) genotyping of at least two of the polynucleotides selected from the group consisting of MTM1, EIF3E, COPS8, ADAMTSL1, CXXC4, RSPO2, OR9Q1, ADAMTS9, KLHDC8A and PRDM9, in the samples of the individuals and awarding the value of 0 for specific homozygous SNP combinations (SNP—Single Nucleotide Polymorphism), which indicates that the blood sample stems from a person which will respond to immunoglobulin (IG) treatment, while awarding the value of 1 for SNP combinations not meeting that criteria, which indicates that the blood sample stems from a person which will not respond to immunoglobulin treatment;e) combining the results of genotyping with results of immuno parameter determination in the calculation of an individual LDA-score (LDA—Linar Discriminant Analysis);f) combining a multiplicity of individual LDA-scores to create a reference Responder Score, which allows discrimination between responders and non-responders.;The method can be employed for determining the likelihood of response of a patient, suffering from a disease, towards immunoglobulin therapy."/> ASSAY AND METHOD FOR PREDICTING THERAPEUTIC EFFICACY OF IMMUNOGLOBULIN THERAPY IN INDIVIDUAL PATIENTS WITH RELAPSING REMITTING MULTIPLE SCLEROSIS (RR-MS)
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首页> 外国专利> ASSAY AND METHOD FOR PREDICTING THERAPEUTIC EFFICACY OF IMMUNOGLOBULIN THERAPY IN INDIVIDUAL PATIENTS WITH RELAPSING REMITTING MULTIPLE SCLEROSIS (RR-MS)

ASSAY AND METHOD FOR PREDICTING THERAPEUTIC EFFICACY OF IMMUNOGLOBULIN THERAPY IN INDIVIDUAL PATIENTS WITH RELAPSING REMITTING MULTIPLE SCLEROSIS (RR-MS)

机译：预测缓解多发性硬化症（RR-MS）的个体患者免疫球蛋白治疗的疗效评估和方法

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A method for generating a reference for determining the likelihood of response of a patient, suffering from a disease, towards immunoglobulin therapy comprising the steps ofa) providing samples of a sufficient number of individuals, in particular at least 10 individuals, the samples containing B- and T-lymphocytes, natural killer cells, invariant T-cells and monocytes of the individuals;b) determination of values of immune parameters which are either static, such as leukocyte subpopulations and cytokine-level in the plasma or functional, like gene expression and cytokine release after lipopolysaccharide (LPS) and/or IVIG stimulation ex vivo;c) the determined values derived from immune parameters of the samples of the individuals are ordered in quartiles and the values belonging to the 1. quartile, values distributed at the low end of the corresponding parameter, are set to “−1”, whereas values distributed in the 4. quartile are set to “+1” for an individual LDA-score calculation and values in between are set to “0”;d) genotyping of at least two of the polynucleotides selected from the group consisting of MTM1, EIF3E, COPS8, ADAMTSL1, CXXC4, RSPO2, OR9Q1, ADAMTS9, KLHDC8A and PRDM9, in the samples of the individuals and awarding the value of 0 for specific homozygous SNP combinations (SNP—Single Nucleotide Polymorphism), which indicates that the blood sample stems from a person which will respond to immunoglobulin (IG) treatment, while awarding the value of 1 for SNP combinations not meeting that criteria, which indicates that the blood sample stems from a person which will not respond to immunoglobulin treatment;e) combining the results of genotyping with results of immuno parameter determination in the calculation of an individual LDA-score (LDA—Linar Discriminant Analysis);f) combining a multiplicity of individual LDA-scores to create a reference Responder Score, which allows discrimination between responders and non-responders.;The method can be employed for determining the likelihood of response of a patient, suffering from a disease, towards immunoglobulin therapy.
机译：一种用于产生用于确定患有疾病的患者对免疫球蛋白疗法反应的可能性的参考的方法，包括以下步骤： a）提供足够数量的个体（尤其是至少10个个体）的样本，样本中包含B -和T淋巴细胞，自然杀伤细胞，个体的不变T细胞和单核细胞; b）确定免疫参数的值静态，例如血浆中的白细胞亚群和细胞因子水平或功能性，例如离体脂多糖（LPS）和/或IVIG刺激后的基因表达和细胞因子释放; c）从个体样本的免疫参数得出的确定值按四分位数排序，并且属于1.四分位数的值（分布在相应参数下端的值）设置为“ -1” ”，而对于单个LDA得分ca，在四分位数中分配的值设置为“ +1”计算值和中间值设置为“ 0”; d）对选自MTM1，EIF3E的至少两个多核苷酸进行基因分型个体样本中的，COPS8，ADAMTSL1，CXXC4，RSPO2，OR9Q1，ADAMTS9，KLHDC8A和PRDM9，并为特定的纯合SNP组合（SNP-单核苷酸多态性）授予0的值，这表明血液样本来源于将对免疫球蛋白（IG）治疗有反应的人，同时为不符合该标准的SNP组合授予1的值，这表明血液样本来源于对免疫球蛋白治疗无反应的人; e）将基因分型的结果与免疫参数确定的结果相结合，计算出单个LDA得分（LDA-Linar判别分析）; f）组合多级各个LDA得分创建参考响应者得分的机率，从而可以区分响应者和非响应者。 ;该方法可用于确定患有以下疾病的患者做出响应的可能性：疾病，转向免疫球蛋白治疗。

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