Novel gene classifiers and uses thereof in autoimmune diseases

Abstract

Disclosed herein are methods of detecting an altered gene expression levels in a subject suspected of having an autoimmune disorder. Further described herein are methods of treating an autoimmune disorder in a subject having an exhibiting an altered gene expression level.

What is claimed is: 
     
         1 . A non-invasive method of detecting an autoimmune disease and/or predicting flare-up, remission or a response to a treatment for, an autoimmune disease:
 a) collecting a tissue sample comprising cellular material from a non-lesional area of skin from a subject suspected of having the autoimmune disease using an adhesive patch sampling of the cellular material from the stratum corneum onto an adhesive patch, wherein the cellular material comprises nucleic acids,   b) isolating nucleic acids from the tissue sample collected from the subject, and   c) detecting the autoimmune disease and/or predicting flare-up, remission or response to a treatment for, the autoimmune disease based on expression levels derived from the isolated nucleic acids.   
     
     
         2 . The method of  claim 1 , wherein (i) the adhesive patch sampling removably adheres the cellular material from the stratum corneum onto an adhesive material on the adhesive patch and/or (ii) the type of cellular material obtained from the adhesive patch sampling comprises cells obtained from the skin no deeper than the stratum corneum. 
     
     
         3 . The method of  claim 1 , wherein an amount of cellular material collected by the adhesive patch sampling is no more than about 1 gram. 
     
     
         4 . The method of  claim 1 , wherein the expression levels of nucleic acids are derived from one or more genes in a gene classifier associated with the immune and/or inflammatory pathways elevated in atopic dermatitis, lupus, or psoriasis. 
     
     
         5 . The method of  claim 4 , wherein the pathways comprise Th1, Th2, Th17, or Th22. 
     
     
         6 . The method of  claim 1 , wherein expression levels of one or more genes from a gene classifier associated with atopic dermatitis are analyzed from the sample, and the gene classifier comprises: (i) IL-13, IL-31, or TSLP; (ii) IL-13R, IL-4R, IL-17, IL-22, CXCL9, CXCL10, CXCLH, S100A7, S100A8, S100A9, CCL17, CCL18, CCL19, CCL26, CCL27, or NOS2; (iii) IL-31RA, CCL17, IL-23A, IL-4R, IL22, IL-13, or IL-13RA1; or (iv) IL-13 pathway constituents or receptors. 
     
     
         7 . The method of  claim 1 , comprising predicting a response to a treatment for the autoimmune disease, wherein the autoimmune disease comprises atopic dermatitis, and the treatment comprises an inhibitor of IL-13, an inhibitor of PDE4, or an inhibitor of IL-31. 
     
     
         8 . The method of  claim 1 , comprising predicting a response to a treatment for the autoimmune disease, wherein the autoimmune disease comprises atopic dermatitis, and the treatment comprises lebrikizumab, tralokinumab, crisaborole, or nemolizumab. 
     
     
         9 . The method of  claim 1 , wherein expression levels of one or more genes from a gene classifier associated with psoriasis are analyzed from the sample, and the gene classifier comprises: (i) IL-17A, IL-17F, IL-8, CXCL5, S100A9, or DEFB4A; (ii) IL-17C, S100A7, IL-17RA, IL-17RC, IL-23A, IL-22, IL-26, IL-24, IL-6, CXCL1, IFN-gamma, IL-31, IL-33, TNFa, LCN2, CCL20, or TNFRSF1A; or (iii) IL-17A, IL-17C, IL-17F, IL-17 receptor, IL-23 A, IL-22, IL-24, IL-6, IL-8, CXCL1, CXCL5, DEFB4A, LCN2, S100A7, TNF-alpha, or TNF-alpha receptor. 
     
     
         10 . The method of  claim 1 , comprising predicting a response to a treatment for the autoimmune disease, wherein the autoimmune disease comprises psoriasis, and the treatment comprises an inhibitor of TNF-alpha, an inhibitor of IL-17A, or an inhibitor of IL-23. 
     
     
         11 . The method of  claim 1 , comprising predicting a response to a treatment for the autoimmune disease, wherein the autoimmune disease comprises psoriasis, and the treatment comprises adalimumab, certolizumab, etanercept, golimumab, and infliximab, ixekizumab (LY2439821), brodalumab (AMG 827), secukinumab, guselkumab, tildrakizumab, or risankizumab. 
     
     
         12 . The method of  claim 1 , wherein expression levels of one or more genes from a gene classifier associated with lupus are analyzed from the sample, and the gene classifier comprises: (i) IFNAJ, IFNA2, IFNA4, 11 ′NR 1, IFNR2, CCL5; or (ii) IFNB1, IFNE, IFNWI, ADAR, IFIT, IFI, IRF, OAS1, TRAM, TNFAIP3, ATG5, TYK2, STAT4, OPN, or KRT. 
     
     
         13 . The method of  claim 1 , comprising predicting a response to a treatment for the autoimmune disease, wherein the autoimmune disease comprises lupus, and the treatment comprises: an antimalarial, dapsone, a retinoid, a corticosteroid, an immunosuppressive drug, thalidomide, a Janus kinase inhibitor, Dapsone, baricitinib, hydroxychloroquine, quinacrine, chloroquine, methotrexate, or azathioprine. 
     
     
         14 . The method of  claim 1 , wherein detecting the presence of, and/or predicting a response to a treatment for, the autoimmune disease comprises: contacting the isolated nucleic acids with a set of probes that recognize one or more genes involved in the cytokine-mediated immune and inflammatory responses, detecting or measuring an amount of binding between the nucleic acids and the set of probes, and comparing the amount of binding between the nucleic acids and the set of probes in the sample relative to a control or threshold amount of binding. 
     
     
         15 . The method of  claim 14 , comprising administering to the subject the treatment for the autoimmune disease when the amount of binding between the nucleic acids and the set of probes is altered in the sample relative to the control or threshold amount of binding. 
     
     
         16 . A method for non-invasively identifying an autoimmune disease, comprising:
 a) identifying a subject suspected of having an autoimmune disease, the subject having lesional and non-lesional areas of skin;   b) applying an adhesive patch to a non-lesional area of the subject's skin in a manner sufficient to adhere a sample of cellular material from the stratum corneum to the adhesive patch, wherein the sample of cellular material comprises nucleic acids;   c) removing the adhesive patch from the subject's skin in a manner sufficient to retain the sample of cellular material adhered to the adhesive patch; and   d) detecting an autoimmune disease and/or predicting flare-up, remission or a response to a treatment for, the autoimmune disease based on expression levels derived from the isolated nucleic acids.   
     
     
         17 . The method of  claim 16 , wherein the autoimmune disease comprises atopic dermatitis, and expression levels of one or more genes from a gene classifier are analyzed from the sample, wherein the gene classifier comprises: (i) IL-13, IL-31, or TSLP; (ii) IL-13R, IL-4R, IL-17, IL-22, CXCL9, CXCL10, CXCLH, S100A7, S100A8, S100A9, CCL17, CCL18, CCL19, CCL26, CCL27, or NOS2; (iii) IL-31RA, CCL17, IL-23A, IL-4R, IL22, IL-13, or IL-13RA1; or (iv) IL-13 pathway constituents or receptors. 
     
     
         18 . The method of  claim 16 , wherein the autoimmune disease comprises psoriasis, and expression levels of one or more genes from a gene classifier are analyzed from the sample, wherein the gene classifier comprises: (i) IL-17A, IL-17F, IL-8, CXCL5, S100A9, or DEFB4A; (ii) IL-17C, S100A7, IL-17RA, IL-17RC, IL-23A, IL-22, IL-26, IL-24, IL-6, CXCL1, IFN-gamma, IL-31, IL-33, TNFa, LCN2, CCL20, or TNFRSF1A; or (iii) IL-17A, IL-17C, IL-17F, IL-17 receptor, IL-23 A, IL-22, IL-24, IL-6, IL-8, CXCL1, CXCL5, DEFB4A, LCN2, S100A7, TNF-alpha, or TNF-alpha receptor. 
     
     
         19 . The method of  claim 16 , wherein the autoimmune disease comprises lupus, and expression levels of one or more genes from a gene classifier are analyzed from the sample, wherein the gene classifier comprises: (i) IFNAJ, IFNA2, IFNA4, 11 ′NR 1, IFNR2, CCL5; or (ii) IFNB1, IFNE, IFNWI, ADAR, IFIT, IFI, IRF, OAS1, TRAM, TNFAIP3, ATG5, TYK2, STAT4, OPN, or KRT. 
     
     
         20 . The method of  claim 16 , wherein
 a) the autoimmune disease comprises atopic dermatitis, and the treatment comprises: an inhibitor of IL-13, an inhibitor of PDE4, an inhibitor of IL-31, lebrikizumab, tralokinumab, crisaborole, or nemolizumab;   b) the autoimmune disease comprises psoriasis, and the treatment comprises: an inhibitor of TNF-alpha, an inhibitor of IL-17A, an inhibitor of IL-23, adalimumab, certolizumab, etanercept, golimumab, and infliximab, ixekizumab (LY2439821), brodalumab (AMG 827), secukinumab, guselkumab, tildrakizumab, or risankizumab; or   c) the autoimmune disease comprises lupus, and the treatment comprises: an antimalarial, dapsone, a retinoid, a corticosteroid, an immunosuppressive drug, thalidomide, a Janus kinase inhibitor, Dapsone, baricitinib, hydroxychloroquine, quinacrine, chloroquine, methotrexate, or azathioprine.