| 摘要 |
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 of 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. |
