NOVEL GENE CLASSIFIERS AND USES THEREOF IN PSORIASIS
Disclosed herein are methods of detecting an altered gene expression levels in a subject suspected of having psoriasis. Further described herein are methods of treating psoriasis in a subject having an exhibiting an altered gene expression level.
1 . A method for preparing nucleic acids from a skin sample useful for detecting a gene expression level of IL-17A, IL-17F, IL-8, CXCL5, S100A9, or DEFB4A in a subject suspected of having psoriasis, comprising:
a) isolating nucleic acids from a skin sample obtained from the subject, where the skin sample comprises cells from the stratum corneum; and
b) detecting the expression level of IL-17A, IL-17F, IL-8, CXCL5, S100A9, or DEFB4A by contacting the isolated nucleic acids with a probe that recognizes IL-17A, IL-17F, IL-8, CXCL5, S100A9, or DEFB4A, and detecting binding between IL-17A, IL-17F, IL-8, CXCL5, S100A9, or DEFB4A or the probe.
2 . The method of claim 1 , wherein the method comprises detecting the expression levels of at least two of IL-17A, IL-17F, IL-8, CXCL5, S100A9, and DEFB4A.
3 . The method of claim 1 , wherein the method comprises detecting the expression levels of at least three of IL-17A, IL-17F, IL-8, CXCL5, S100A9, and DEFB4A.
4 . The method of claim 1 , wherein the method comprises:
detecting the expression levels of IL-17A, IL-17F, IL-8, CXCL5, S100A9, and DEFB4A;
detecting the expression levels of IL-17A, IL-17F, IL-8, CXCL5, and S100A9;
detecting the expression levels of IL-17A, IL-17F, IL-8, and CXCL5;
detecting the expression levels of IL-17A, IL-17F, and IL-8; or
detecting the expression levels of IL-17A, and IL-17F.
5 . The method of claim 1 , wherein the expression level is an up-regulated gene expression level, compared to a gene expression level of an equivalent gene from a control sample.
6 . The method of claim 2 , wherein at least two of IL-17A, IL-17F, IL-8, CXCL5, S100A9, or DEFB4A are used in a gene classifier.
7 . The method of claim 6 , wherein b) comprises detecting the expression levels of at least two of IL-17A, IL-17F, IL-8, CXCL5, S100A9, or DEFB4A by contacting the isolated nucleic acids with a set of probes that recognizes at least two of IL-17A, IL-17F, IL-8, CXCL5, S100A9, or DEFB4A, and detecting binding between at least two of IL-17A, IL-17F, IL-8, CXCL5, S100A9, or DEFB4A and the set of probes.
8 . The method of claim 7 , wherein the set of probes recognizes at least two but no more than six genes.
9 . The method of claim 6 , wherein the gene classifier comprises IL-17A, IL-17F, IL-8, CXCL5, S100A9, and DEFB4A.
10 . The method of claim 9 , wherein the expression level comprises an upregulated gene expression level of IL-17A, IL-17F, IL-8, CXCL5, S100A9, and DEFB4A, relative to one or more controls.
11 . The method of claim 1 , further comprising:
c) detecting the expression level of IL-17C, S100A7, IL-17RA, IL-17RC, IL-23A, IL-22, IL-26, IL-24, IL-6, CXCL1, IFN-gamma, IL-31, IL-33, TNFα, LCN2, CCL20, or TNFRSF1A, by contacting the isolated nucleic acids with an additional probe that recognizes IL-17C, S100A7, IL-17RA, IL-17RC, IL-23A, IL-22, IL-26, IL-24, IL-6, CXCL1, IFN-gamma, IL-31, IL-33, TNFα, LCN2, CCL20, or TNFRSF1A, and detecting binding between IL-17C, S100A7, IL-17RA, IL-17RC, IL-23A, IL-22, IL-26, IL-24, IL-6, CXCL1, IFN-gamma, IL-31, IL-33, TNFα, LCN2, CCL20, or TNFRSF1A and the additional probe.
12 . The method of claim 11 , wherein IL-17A, IL-17F, IL-8, CXCL5, S100A9, or DEFB4A is used in a first gene classifier, and one or more of the following genes is used in a second gene classifier: IL-17C, S100A7, IL-17RA, IL-17RC, IL-23A, IL-22, IL-26, IL-24, IL-6, CXCL1, IFN-gamma, IL-31, IL-33, TNFα, LCN2, CCL20, or TNFRSF1A.
13 . The method of claim 12 , wherein two or more of the following genes is used in the second gene classifier: IL-17C, S100A7, IL-17RA, IL-17RC, IL-23A, IL-22, IL-26, IL-24, IL-6, CXCL1, IFN-gamma, IL-31, IL-33, TNFα, LCN2, CCL20, or TNFRSF1A.
14 . The method of claim 13 , wherein c) comprises detecting the expression levels of the two or more genes from the second gene classifier by contacting the isolated nucleic acids with a set of probes that recognizes the two or more genes from the second gene classifier, and detecting binding between the two or more genes from the second gene classifier and the set of probes.
15 . The method of claim 1 , wherein the cells from the stratum corneum comprise keratinocytes.
16 . The method of claim 1 , wherein an amount of the nucleic acids isolated from the skin sample is from about 100 picograms to about 1 microgram.
17 . The method of claim 1 , wherein the skin sample is obtained by applying an adhesive patch to a skin region of the subject in a manner sufficient to adhere cells to the adhesive patch, and removing the adhesive patch from the skin region in a manner sufficient to retain the adhered cells to the adhesive patch.
18 . The method of claim 17 , further comprising:
c) determining a likelihood that the subject has psoriasis based on the expression level.
19 . The method of claim 18 , further comprising:
d) administering a psoriasis treatment to the subject based on the determination.
20 . The method of claim 19 , wherein the psoriasis treatment comprises an antibody.