BIOMARKERS FOR DIAGNOSIS AND TREATMENT OF ACNE VULGARIS
Described herein are methods, systems, platforms, and kits for the characterization, assessment, diagnosis and treatment of acne vulgaris. Among the methods provided are methods of identifying a gene expression profile for acne vulgaris and biomarkers for monitoring treatment. Also provided are methods, systems, platforms, and kits for monitoring efficacy of a treatment and methods for selecting a treatment regimen.
1 . A method for characterizing tissue comprising:
a) obtaining tissue from an adhesive tape that had been applied to a subject in a manner sufficient to isolate an epidermal sample adhering to the adhesive tape, wherein the epidermal sample comprises one or more genes listed in Tables 3, 6, 7, 8, or 9 or a gene product expressed by one or more genes listed in Tables 3, 6, 7, 8, or 9; and
b) characterizing the subject as having or likely having acne vulgaris based on the relative amount of the gene or gene product present in the epidermal sample.
2 . The method of claim 1 , provided that the gene or gene product expressed by a gene is selected from Table 3 or 6.
3 . The method of claim 1 , provided that the gene or gene product expressed by a gene is selected from Table 7, 8, or 9.
4 . The method of claim 1 , provided that the gene or gene product expressed by a gene is selected from the group consisting of defensin beta 4 (DEFB4), S100 calcium binding protein A8 (calgranulin B) (S100A8), Transcribed locus (GenBank Accession AI741601), SH3-domain GRB2-like 3 (GenBank Accession AK098337), cysteinyl leukotriene receptor 1 (CYSLTR1), ubiquitin-like modifier activating enzyme 6 (UBA6), programmed cell death 7 (PDCD7), Wilms tumor 1 associated protein (WTAP), aprataxin (APTX), serpin peptidase inhibitor clade B (ovalbumin) member 3 (SERPINB3), solute carrier family 16 member 10 (SLC16A10), interleukin 8 (IL-8), cystatin E/M (CST6), serine peptidase inhibitor Kazal type 5 (SPINK5), TIMP metallopeptidase inhibitor 3 (TIMP3), caspase recruitment domain family, member 18 (CARD18), serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, andtitrypsin) member 3 (SERPINA3), WAP four-disulfide core domain 3 (WFCD3), cysteine rich transmembrane BMP regulator 1 (chordin-like) (CRIM1), serine peptidase inhibitor Kunitz type 2 (SPINT2), and combinations thereof. In some embodiments, the gene is, or in the case of an expression product, the expression product is expressed by, a gene selected from the group consisting of S100 calcium binding protein A8 (calgranulin B) (S100A8), Transcribed locus (GenBank Accession AI741601), SH3-domain GRB2-like 3 (GenBank Accession AK098337), cysteinyl leukotriene receptor 1 (CYSLTR1), ubiquitin-like modifier activating enzyme 6 (UBA6), programmed cell death 7 (PDCD7), Wilms tumor 1 associated protein (WTAP), aprataxin (APTX), serpin peptidase inhibitor clade B (ovalbumin) member 3 (SERPINB3), solute carrier family 16 member 10 (SLC16A10), cystatin E/M (CST6), serine peptidase inhibitor Kazal type 5 (SPINK5), TIMP metallopeptidase inhibitor 3 (TIMP3), caspase recruitment domain family, member 18 (CARD18), serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, andtitrypsin) member 3 (SERPINA3), WAP four-disulfide core domain 3 (WFCD3), cysteine rich transmembrane BMP regulator 1 (chordin-like) (CRIM1), serine peptidase inhibitor Kunitz type 2 (SPINT2), and combinations thereof.
5 . The method of claim 1 , provided that the gene or gene product is one that has increased expression in inflammatory acne lesions compared to normal skin.
6 . The method of claim 1 , provided that the gene or gene product is one that has decreased expression in inflammatory acne lesions compared to normal skin.
7 . The method of claim 1 , further comprising detecting a relative amount of the gene or gene product compared to a control.
8 . The method of claim 1 , provided that the epidermal sample comprises a gene product that is an RNA molecule.
9 . The method of claim 1 , further comprising treating the subject for acne vulgaris.
10 . The method of claim 9 , provided that the treatment comprises an antiseptic, an antibiotic, a retinoid, a hormone, an anti-inflammatory agent, an aldosterone receptor antagonist, a comedo an extraction, a surgery, a dermabrasion, or a phototherapy.
11 . A method for diagnosing acne or characterizing sensitivity or likelihood of a subject to developing acne lesions comprising:
a) applying an adhesive tape to a target area of the skin of the subject in a manner sufficient to isolate an epidermal sample adhering to the adhesive tape, wherein the epidermal sample comprises one or more genes listed in any of Tables 3, 6, 7, 8, or 9 or a gene product expressed by one or more genes listed in any of Tables 3, 6, 7, 8, or 9; and
b) characterizing the subject as having sensitivity to developing acne lesions based on the gene or gene product present in the epidermal sample.
12 . The method of claim 11 , provided that the gene or gene product expressed by a gene is selected from the group consisting of defensin beta 4 (DEFB4), S100 calcium binding protein A8 (calgranulin B) (S100A8), Transcribed locus, SH3-domain GRB2-like 3, cysteinyl leukotriene receptor 1 (CYSLTR1), hypothetical protein FLJ10808, programmed cell death 7 (PDCD7), Wilms tumor 1 associated protein (WTAP), aprataxin (APTX), serpin peptidase inhibitor clade B (ovalbumin) member 3 (SERPINB3), solute carrier family 16 member 10 (SLC16A10), interleukin 8 (IL-8), cystatin E/M (CST6), serine peptidase inhibitor Kazal type 5 (SPINK5), TIMP metallopeptidase inhibitor 3 (TIMP3), ICEBERG caspase-1 inhibitor, serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, andtitrypsin) member 3 (SERPINA3), WAP four-disulfide core domain 3 (WFCD3), cysteine rich transmembrane BMP regulator 1 (chordin-like) (CRIM1), serine peptidase inhibitor Kunitz type 2 (SPINT2), and combinations thereof. In some embodiments, the gene is, or the gene product is expressed by, a gene selected from the group consisting of S100 calcium binding protein A8 (calgranulin B) (S100A8), Transcribed locus (GenBank Accession AI741601), SH3-domain GRB2-like 3 (GenBank Accession AK098337), cysteinyl leukotriene receptor 1 (CYSLTR1), ubiquitin-like modifier activating enzyme 6 (UBA6), programmed cell death 7 (PDCD7), Wilms tumor 1 associated protein (WTAP), aprataxin (APTX), serpin peptidase inhibitor clade B (ovalbumin) member 3 (SERPINB3), solute carrier family 16 member 10 (SLC16A10), cystatin E/M (CST6), serine peptidase inhibitor Kazal type 5 (SPINK5), TIMP metallopeptidase inhibitor 3 (TIMP3), caspase recruitment domain family, member 18 (CARD18), serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, andtitrypsin) member 3 (SERPINA3), WAP four-disulfide core domain 3 (WFCD3), cysteine rich transmembrane BMP regulator 1 (chordin-like) (CRIM1), serine peptidase inhibitor Kunitz type 2 (SPINT2), and combinations thereof.
13 . The method of claim 11 , provided that the gene or gene product is one that has increased expression in inflammatory acne lesions compared to normal skin.
14 . The method of claim 11 , provided that the gene or gene product is one that has decreased expression in inflammatory acne lesions compared to normal skin.
15 . The method of claim 11 , further comprising detecting a relative amount of the gene or gene product compared to a control.
16 . The method of claim 11 , provided that the nucleic acid molecule is an RNA molecule.
17 . A kit for diagnosis of a complication, characterization of tissue, or determining a response or likely response of a subject to treatment for acne vulgaris comprising a skin sample collection device and one or more probes or primers that selectively bind to a gene listed in any of Tables 3, 6, 7, 8, or 9 or a gene product expressed by one or more genes listed in any of Tables 3, 6, 7, 8, or 9.
18 . The kit of claim 17 , provided that the one or more probes or primers selectively binds to a nucleic acid molecule that is RNA.
19 . The kit of claim 17 , provided that the one or more probes or primers are detectably labeled.
20 . The kit of claim 17 , provided that the gene or gene product expressed by a gene is selected from the group consisting of defensin beta 4 (DEFB4), S100 calcium binding protein A8 (calgranulin B) (S100A8), Transcribed locus, SH3-domain GRB2-like 3, cysteinyl leukotriene receptor 1 (CYSLTR1), hypothetical protein FLJ10808, programmed cell death 7 (PDCD7), Wilms tumor 1 associated protein (WTAP), aprataxin (APTX), serpin peptidase inhibitor clade B (ovalbumin) member 3 (SERPINB3), solute carrier family 16 member 10 (SLC16A10), interleukin 8 (IL-8), cystatin E/M (CST6), serine peptidase inhibitor Kazal type 5 (SPINK5), TIMP metallopeptidase inhibitor 3 (TIMP3), ICEBERG caspase-1 inhibitor, serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, andtitrypsin) member 3 (SERPINA3), WAP four-disulfide core domain 3 (WFCD3), cysteine rich transmembrane BMP regulator 1 (chordin-like) (CRIM1), serine peptidase inhibitor Kunitz type 2 (SPINT2), and combinations thereof. In some embodiments, the gene is, or the gene product is expressed by, a gene selected from the group consisting of S100 calcium binding protein A8 (calgranulin B) (S100A8), Transcribed locus (GenBank Accession AI741601), SH3-domain GRB2-like 3 (GenBank Accession AK098337), cysteinyl leukotriene receptor 1 (CYSLTR1), ubiquitin-like modifier activating enzyme 6 (UBA6), programmed cell death 7 (PDCD7), Wilms tumor 1 associated protein (WTAP), aprataxin (APTX), serpin peptidase inhibitor clade B (ovalbumin) member 3 (SERPINB3), solute carrier family 16 member 10 (SLC16A10), cystatin E/M (CST6), serine peptidase inhibitor Kazal type 5 (SPINK5), TIMP metallopeptidase inhibitor 3 (TIMP3), caspase recruitment domain family, member 18 (CARD18), serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, andtitrypsin) member 3 (SERPINA3), WAP four-disulfide core domain 3 (WFCD3), cysteine rich transmembrane BMP regulator 1 (chordin-like) (CRIM1), serine peptidase inhibitor Kunitz type 2 (SPINT2), and combinations thereof.