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Targeted Therapies and Biomarkers for Personalized Treatment of Psoriasis

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Personalized Treatment Options in Dermatology

Abstract

Four decades of clinical, translational, and basic psoriasis research have greatly advanced our understanding of psoriasis pathogenesis. Psoriasis is a complex disease resulting from the interaction of genetic, environmental, and immunological factors. Several psoriasis susceptibility genes and critical immunological drivers have been identified, and some of these findings have resulted in novel target therapies which have increased the number of effective therapeutic options available to clinicians and patients. Nonetheless, biologic therapies are expensive, associated with side effects, and there is still a sizable fraction of nonresponder patients, thus calling for increasingly effective and safe therapies, as well as biomarkers for patients’ stratification to maximize the chances of therapy success. A continuous effort is ongoing to translate basic and clinical findings, increasingly obtained with the support of novel high-throughput technologies and powerful analytical tools, into clinical practice to benefit psoriasis patients. In line with a general shift from reaction to prevention medicine and from population to personalized medicine, stratified medicine approaches in psoriasis are no longer far-fetched. Here we review the psoriasis literature, describing the recent elucidation of critical pathogenic mechanisms, their translation into targeted therapies, and how they are being exploited in the quest for psoriasis biomarkers to guide patients’ stratification.

Federica Villanova and Paola Di Meglio contributed equally

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References

  1. Nestle FO, Kaplan DH, Barker J. Psoriasis. N Engl J Med. 2009;361(5):496–509.

    CAS  PubMed  Google Scholar 

  2. Lowes MA, Suarez-Farinas M, Krueger JG. Immunology of psoriasis. Annu Rev Immunol. 2014;32:227–55.

    PubMed Central  CAS  PubMed  Google Scholar 

  3. Kelkar SS, Reineke TM. Theranostics: combining imaging and therapy. Bioconjug Chem. 2011;22(10):1879–903.

    CAS  PubMed  Google Scholar 

  4. Parisi R, Symmons DP, Griffiths CE, Ashcroft DM. Global epidemiology of psoriasis: a systematic review of incidence and prevalence. J Invest Dermatol. 2013;133(2):377–85.

    CAS  PubMed  Google Scholar 

  5. Henseler T, Christophers E. Psoriasis of early and late onset: characterization of two types of psoriasis vulgaris. J Am Acad Dermatol. 1985;13(3):450–6.

    CAS  PubMed  Google Scholar 

  6. Hart PH, Gorman S, Finlay-Jones JJ. Modulation of the immune system by UV radiation: more than just the effects of vitamin D? Nat Rev Immunol. 2011;11(9):584–96.

    CAS  PubMed  Google Scholar 

  7. Griffiths CE, Christophers E, Barker JN, Chalmers RJ, Chimenti S, Krueger GG, et al. A classification of psoriasis vulgaris according to phenotype. Br J Dermatol. 2007;156(2):258–62.

    CAS  PubMed  Google Scholar 

  8. Perera GK, Di Meglio P, Nestle FO. Psoriasis. Annu Rev Pathol. 2012;7:385–422.

    CAS  PubMed  Google Scholar 

  9. Marrakchi S, Guigue P, Renshaw BR, Puel A, Pei XY, Fraitag S, et al. Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis. N Engl J Med. 2011;365(7):620–8.

    CAS  PubMed  Google Scholar 

  10. Onoufriadis A, Simpson MA, Pink AE, Di Meglio P, Smith CH, Pullabhatla V, et al. Mutations in IL36RN/IL1F5 are associated with the severe episodic inflammatory skin disease known as generalized pustular psoriasis. Am J Hum Genet. 2011;89(3):432–7.

    PubMed Central  CAS  PubMed  Google Scholar 

  11. Anandarajah AP, Ritchlin CT. The diagnosis and treatment of early psoriatic arthritis. Nat Rev Rheumatol. 2009;5(11):634–41.

    CAS  PubMed  Google Scholar 

  12. Gladman DD, Antoni C, Mease P, Clegg DO, Nash P. Psoriatic arthritis: epidemiology, clinical features, course, and outcome. Ann Rheum Dis. 2005;64 Suppl 2:ii14–7.

    PubMed Central  PubMed  Google Scholar 

  13. Ellinghaus E, Stuart PE, Ellinghaus D, Nair RP, Debrus S, Raelson JV, et al. Genome-wide meta-analysis of psoriatic arthritis identifies susceptibility locus at REL. J Invest Dermatol. 2012;132(4):1133–40.

    PubMed Central  CAS  PubMed  Google Scholar 

  14. Eder L, Chandran V, Pellett F, Pollock R, Shanmugarajah S, Rosen CF, et al. IL13 gene polymorphism is a marker for psoriatic arthritis among psoriasis patients. Ann Rheum Dis. 2011;70(9):1594–8.

    CAS  PubMed  Google Scholar 

  15. Brandrup F, Hauge M, Henningsen K, Eriksen B. Psoriasis in an unselected series of twins. Arch Dermatol. 1978;114(6):874–8.

    CAS  PubMed  Google Scholar 

  16. Duffy DL, Spelman LS, Martin NG. Psoriasis in Australian twins. J Am Acad Dermatol. 1993;29(3):428–34.

    CAS  PubMed  Google Scholar 

  17. Farber EM, Nall ML, Watson W. Natural history of psoriasis in 61 twin pairs. Arch Dermatol. 1974;109(2):207–11.

    CAS  PubMed  Google Scholar 

  18. Lonnberg AS, Skov L, Skytthe A, Kyvik KO, Pedersen OB, Thomsen SF. Heritability of psoriasis in a large twin sample. Br J Dermatol. 2013;169:412–6.

    CAS  PubMed  Google Scholar 

  19. Capon F, Bijlmakers MJ, Wolf N, Quaranta M, Huffmeier U, Allen M, et al. Identification of ZNF313/RNF114 as a novel psoriasis susceptibility gene. Hum Mol Genet. 2008;17(13):1938–45.

    PubMed Central  CAS  PubMed  Google Scholar 

  20. Ellinghaus E, Ellinghaus D, Stuart PE, Nair RP, Debrus S, Raelson JV, et al. Genome-wide association study identifies a psoriasis susceptibility locus at TRAF3IP2. Nat Genet. 2010;42(11):991–5.

    PubMed Central  CAS  PubMed  Google Scholar 

  21. Nair RP, Duffin KC, Helms C, Ding J, Stuart PE, Goldgar D, et al. Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways. Nat Genet. 2009;41(2):199–204.

    PubMed Central  CAS  PubMed  Google Scholar 

  22. Strange A, Capon F, Spencer CC, Knight J, Weale ME, Allen MH, et al. A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1. Nat Genet. 2010;42(11):985–90.

    PubMed Central  CAS  PubMed  Google Scholar 

  23. Stuart PE, Nair RP, Ellinghaus E, Ding J, Tejasvi T, Gudjonsson JE, et al. Genome-wide association analysis identifies three psoriasis susceptibility loci. Nat Genet. 2010;42(11):1000–4.

    PubMed Central  CAS  PubMed  Google Scholar 

  24. Zhang XJ, Huang W, Yang S, Sun LD, Zhang FY, Zhu QX, et al. Psoriasis genome-wide association study identifies susceptibility variants within LCE gene cluster at 1q21. Nat Genet. 2009;41(2):205–10.

    CAS  PubMed  Google Scholar 

  25. de Cid R, Riveira-Munoz E, Zeeuwen PL, Robarge J, Liao W, Dannhauser EN, et al. Deletion of the late cornified envelope LCE3B and LCE3C genes as a susceptibility factor for psoriasis. Nat Genet. 2009;41(2):211–5.

    PubMed Central  PubMed  Google Scholar 

  26. Huffmeier U, Uebe S, Ekici AB, Bowes J, Giardina E, Korendowych E, et al. Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis. Nat Genet. 2010;42(11):996–9.

    PubMed Central  PubMed  Google Scholar 

  27. Tsoi LC, Spain SL, Knight J, Ellinghaus E, Stuart PE, Capon F, et al. Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity. Nat Genet. 2012;44(12):1341–8.

    PubMed Central  CAS  PubMed  Google Scholar 

  28. Ellinghaus D, Ellinghaus E, Nair RP, Stuart PE, Esko T, Metspalu A, et al. Combined analysis of genome-wide association studies for Crohn disease and psoriasis identifies seven shared susceptibility loci. Am J Hum Genet. 2012;90(4):636–47.

    PubMed Central  CAS  PubMed  Google Scholar 

  29. Sun LD, Cheng H, Wang ZX, Zhang AP, Wang PG, Xu JH, et al. Association analyses identify six new psoriasis susceptibility loci in the Chinese population. Nat Genet. 2010;42(11):1005–9.

    PubMed Central  CAS  PubMed  Google Scholar 

  30. Nair RP, Stuart P, Henseler T, Jenisch S, Chia NV, Westphal E, et al. Localization of psoriasis-susceptibility locus PSORS1 to a 60-kb interval telomeric to HLA-C. Am J Hum Genet. 2000;66(6):1833–44.

    PubMed Central  CAS  PubMed  Google Scholar 

  31. Trembath RC, Clough RL, Rosbotham JL, Jones AB, Camp RD, Frodsham A, et al. Identification of a major susceptibility locus on chromosome 6p and evidence for further disease loci revealed by a two stage genome-wide search in psoriasis. Hum Mol Genet. 1997;6(5):813–20.

    CAS  PubMed  Google Scholar 

  32. Nair RP, Stuart PE, Nistor I, Hiremagalore R, Chia NV, Jenisch S, et al. Sequence and haplotype analysis supports HLA-C as the psoriasis susceptibility 1 gene. Am J Hum Genet. 2006;78(5):827–51.

    PubMed Central  CAS  PubMed  Google Scholar 

  33. Clop A, Bertoni A, Spain SL, Simpson MA, Pullabhatla V, Tonda R, et al. An in-depth characterization of the major psoriasis susceptibility locus identifies candidate susceptibility alleles within an HLA-C enhancer element. PLoS One. 2013;8(8):e71690.

    PubMed Central  CAS  PubMed  Google Scholar 

  34. Capon F, Burden AD, Trembath RC, Barker JN. Psoriasis and other complex trait dermatoses: from Loci to functional pathways. J Invest Dermatol. 2012;132(3 Pt 2):915–22.

    PubMed Central  CAS  PubMed  Google Scholar 

  35. Di Cesare A, Di Meglio P, Nestle FO. The IL-23/Th17 axis in the immunopathogenesis of psoriasis. J Invest Dermatol. 2009;129(6):1339–50.

    PubMed  Google Scholar 

  36. Di Meglio P, Di Cesare A, Laggner U, Chu CC, Napolitano L, Villanova F, et al. The IL23R R381Q gene variant protects against immune-mediated diseases by impairing IL-23-induced Th17 effector response in humans. PLoS One. 2011;6(2):e17160.

    PubMed Central  PubMed  Google Scholar 

  37. Di Meglio P, Villanova F, Napolitano L, Tosi I, Terranova Barberio M, Mak RK, et al. The IL23R A/Gln381 allele promotes IL-23 unresponsiveness in human memory T-helper 17 cells and impairs Th17 responses in psoriasis patients. J Invest Dermatol. 2013;133(10):2381–9.

    PubMed Central  PubMed  Google Scholar 

  38. Di Meglio P, Perera GK, Nestle FO. The multitasking organ: recent insights into skin immune function. Immunity. 2011;35(6):857–69.

    PubMed  Google Scholar 

  39. Lowes MA, Russell CB, Martin DA, Towne JE, Krueger JG. The IL-23/T17 pathogenic axis in psoriasis is amplified by keratinocyte responses. Trends Immunol. 2013;34(4):174–81.

    PubMed Central  CAS  PubMed  Google Scholar 

  40. Lande R, Gregorio J, Facchinetti V, Chatterjee B, Wang YH, Homey B, et al. Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature. 2007;449(7162):564–9.

    CAS  PubMed  Google Scholar 

  41. Ganguly D, Chamilos G, Lande R, Gregorio J, Meller S, Facchinetti V, et al. Self-RNA-antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8. J Exp Med. 2009;206(9):1983–94.

    PubMed Central  CAS  PubMed  Google Scholar 

  42. Lowes MA, Kikuchi T, Fuentes-Duculan J, Cardinale I, Zaba LC, Haider AS, et al. Psoriasis vulgaris lesions contain discrete populations of Th1 and Th17 T cells. J Invest Dermatol. 2008;128(5):1207–11.

    CAS  PubMed  Google Scholar 

  43. Kagami S, Rizzo HL, Lee JJ, Koguchi Y, Blauvelt A. Circulating Th17, Th22, and Th1 cells are increased in psoriasis. J Invest Dermatol. 2010;130(5):1373–83.

    PubMed Central  CAS  PubMed  Google Scholar 

  44. Austin LM, Ozawa M, Kikuchi T, Walters IB, Krueger JG. The majority of epidermal T cells in Psoriasis vulgaris lesions can produce type 1 cytokines, interferon-gamma, interleukin-2, and tumor necrosis factor-alpha, defining TC1 (cytotoxic T lymphocyte) and TH1 effector populations: a type 1 differentiation bias is also measured in circulating blood T cells in psoriatic patients. J Invest Dermatol. 1999;113(5):752–9.

    CAS  PubMed  Google Scholar 

  45. Kryczek I, Bruce AT, Gudjonsson JE, Johnston A, Aphale A, Vatan L, et al. Induction of IL-17+ T cell trafficking and development by IFN-gamma: mechanism and pathological relevance in psoriasis. J Immunol. 2008;181(7):4733–41.

    PubMed Central  CAS  PubMed  Google Scholar 

  46. Ortega C, Fernandez AS, Carrillo JM, Romero P, Molina IJ, Moreno JC, et al. IL-17-producing CD8+ T lymphocytes from psoriasis skin plaques are cytotoxic effector cells that secrete Th17-related cytokines. J Leukoc Biol. 2009;86(2):435–43.

    CAS  PubMed  Google Scholar 

  47. Hijnen D, Knol EF, Gent YY, Giovannone B, Beijn SJ, Kupper TS, et al. CD8(+) T cells in the lesional skin of atopic dermatitis and psoriasis patients are an important source of IFN-gamma, IL-13, IL-17, and IL-22. J Invest Dermatol. 2013;133(4):973–9.

    CAS  PubMed  Google Scholar 

  48. Cai Y, Shen X, Ding C, Qi C, Li K, Li X, et al. Pivotal role of dermal IL-17-producing gammadelta T cells in skin inflammation. Immunity. 2011;35(4):596–610.

    PubMed Central  CAS  PubMed  Google Scholar 

  49. Laggner U, Di Meglio P, Perera GK, Hundhausen C, Lacy KE, Ali N, et al. Identification of a novel proinflammatory human skin-homing Vgamma9Vdelta2 T cell subset with a potential role in psoriasis. J Immunol. 2011;187(5):2783–93.

    PubMed Central  CAS  PubMed  Google Scholar 

  50. Villanova F, Flutter B, Tosi I, Grys K, Sreeneebus H, Perera GK, et al. Characterization of innate lymphoid cells in human skin and blood demonstrates increase of NKp44+ ILC3 in psoriasis. J Invest Dermatol. 2014;134(4):984–91.

    PubMed Central  CAS  PubMed  Google Scholar 

  51. Dyring-Andersen B, Geisler C, Agerbeck C, Lauritsen JP, Gudjonsdottir SD, Skov L, et al. Increased number and frequency of group 3 innate lymphoid cells in nonlesional psoriatic skin. Br J Dermatol. 2014;170(3):609–16.

    CAS  PubMed  Google Scholar 

  52. Teunissen MB, Munneke JM, Bernink JH, Spuls PI, Res PC, Te Velde A, et al. Composition of Innate Lymphoid Cell (ILC) Subsets in the human skin: Enrichment of NCR ILC3 in lesional skin and blood of psoriasis patients. J Invest Dermatol. 2014;134:2351–60.

    CAS  PubMed  Google Scholar 

  53. Lin AM, Rubin CJ, Khandpur R, Wang JY, Riblett M, Yalavarthi S, et al. Mast cells and neutrophils release IL-17 through extracellular trap formation in psoriasis. J Immunol. 2011;187(1):490–500.

    PubMed Central  CAS  PubMed  Google Scholar 

  54. Wilson NJ, Boniface K, Chan JR, McKenzie BS, Blumenschein WM, Mattson JD, et al. Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat Immunol. 2007;8(9):950–7.

    CAS  PubMed  Google Scholar 

  55. Wolf R, Mascia F, Dharamsi A, Howard OM, Cataisson C, Bliskovski V, et al. Gene from a psoriasis susceptibility locus primes the skin for inflammation. Sci Transl Med. 2010;2(61):61ra90.

    CAS  PubMed  Google Scholar 

  56. Zheng Y, Danilenko DM, Valdez P, Kasman I, Eastham-Anderson J, Wu J, et al. Interleukin-22, a T(H)17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature. 2007;445(7128):648–51.

    CAS  PubMed  Google Scholar 

  57. Ma HL, Liang S, Li J, Napierata L, Brown T, Benoit S, et al. IL-22 is required for Th17 cell-mediated pathology in a mouse model of psoriasis-like skin inflammation. J Clin Invest. 2008;118(2):597–607.

    PubMed Central  CAS  PubMed  Google Scholar 

  58. Schlapbach C, Gehad A, Yang C, Watanabe R, Guenova E, Teague JE, et al. Human TH9 cells are skin-tropic and have autocrine and paracrine proinflammatory capacity. Sci Transl Med. 2014;6(219):219ra8.

    PubMed Central  PubMed  Google Scholar 

  59. Griffiths CE, Clark CM, Chalmers RJ, Li Wan Po A, Williams HC. A systematic review of treatments for severe psoriasis. Health Technol Assess. 2000;4(40):1–125.

    CAS  PubMed  Google Scholar 

  60. Mueller W, Herrmann B. Cyclosporin A for psoriasis. N Engl J Med. 1979;301(10):555.

    CAS  PubMed  Google Scholar 

  61. Amor KT, Ryan C, Menter A. The use of cyclosporine in dermatology: part I. J Am Acad Dermatol. 2010;63(6):925–46; quiz 47–8.

    CAS  PubMed  Google Scholar 

  62. Gupta AK, Baadsgaard O, Ellis CN, Voorhees JJ, Cooper KD. Lymphocytes and macrophages of the epidermis and dermis in lesional psoriatic skin, but not epidermal Langerhans cells, are depleted by treatment with cyclosporin A. Arch Dermatol Res. 1989;281(4):219–26.

    CAS  PubMed  Google Scholar 

  63. Gottlieb SL, Heftler NS, Gilleaudeau P, Johnson R, Vallat VP, Wolfe J, et al. Short-contact anthralin treatment augments therapeutic efficacy of cyclosporine in psoriasis: a clinical and pathologic study. J Am Acad Dermatol. 1995;33(4):637–45.

    CAS  PubMed  Google Scholar 

  64. Edwards BD, Andrew SM, O’Driscoll JB, Chalmers RJ, Ballardie FW, Freemont AJ. Changes in numbers of epidermal cell adhesion molecules caused by oral cyclosporin in psoriasis. J Clin Pathol. 1993;46(8):713–7.

    PubMed Central  CAS  PubMed  Google Scholar 

  65. Burdmann EA, Andoh TF, Yu L, Bennett WM. Cyclosporine nephrotoxicity. Semin Nephrol. 2003;23(5):465–76.

    CAS  PubMed  Google Scholar 

  66. Colombo MD, Cassano N, Bellia G, Vena GA. Cyclosporine regimens in plaque psoriasis: an overview with special emphasis on dose, duration, and old and new treatment approaches. Sci World J. 2013;2013:805705.

    CAS  Google Scholar 

  67. Weinstein GD. Methotrexate. Ann Intern Med. 1977;86(2):199–204.

    CAS  PubMed  Google Scholar 

  68. Prodanovic EM, Korman NJ. Traditional systemic therapy I: methotrexate and cyclosporine. In: Treatment of psoriasis. Basel/Boston: Birkhauser; 2008. p. 103–20.

    Google Scholar 

  69. Shen S, O’Brien T, Yap LM, Prince HM, McCormack CJ. The use of methotrexate in dermatology: a review. Australas J Dermatol. 2012;53(1):1–18.

    PubMed  Google Scholar 

  70. Heydendael VM, Spuls PI, Opmeer BC, de Borgie CA, Reitsma JB, Goldschmidt WF, et al. Methotrexate versus cyclosporine in moderate-to-severe chronic plaque psoriasis. N Engl J Med. 2003;349(7):658–65.

    CAS  PubMed  Google Scholar 

  71. Ramirez-Fort MK, Levin AA, Au SC, Gottlieb AB. Continuous versus intermittent therapy for moderate-to-severe psoriasis. Clin Exp Rheumatol. 2013;31(4 Suppl 78):S63–70.

    PubMed  Google Scholar 

  72. Krueger GG, Papp KA, Stough DB, Loven KH, Gulliver WP, Ellis CN. A randomized, double-blind, placebo-controlled phase III study evaluating efficacy and tolerability of 2 courses of alefacept in patients with chronic plaque psoriasis. J Am Acad Dermatol. 2002;47(6):821–33.

    PubMed  Google Scholar 

  73. Lebwohl M, Christophers E, Langley R, Ortonne JP, Roberts J, Griffiths CE. An international, randomized, double-blind, placebo-controlled phase 3 trial of intramuscular alefacept in patients with chronic plaque psoriasis. Arch Dermatol. 2003;139(6):719–27.

    CAS  PubMed  Google Scholar 

  74. Oh CJ, Das KM, Gottlieb AB. Treatment with anti-tumor necrosis factor alpha (TNF-alpha) monoclonal antibody dramatically decreases the clinical activity of psoriasis lesions. J Am Acad Dermatol. 2000;42(5 Pt 1):829–30.

    CAS  PubMed  Google Scholar 

  75. Leonardi CL, Powers JL, Matheson RT, Goffe BS, Zitnik R, Wang A, et al. Etanercept as monotherapy in patients with psoriasis. N Engl J Med. 2003;349(21):2014–22.

    CAS  PubMed  Google Scholar 

  76. Papp KA, Tyring S, Lahfa M, Prinz J, Griffiths CE, Nakanishi AM, et al. A global phase III randomized controlled trial of etanercept in psoriasis: safety, efficacy, and effect of dose reduction. Br J Dermatol. 2005;152(6):1304–12.

    CAS  PubMed  Google Scholar 

  77. Tyring S, Gottlieb A, Papp K, Gordon K, Leonardi C, Wang A, et al. Etanercept and clinical outcomes, fatigue, and depression in psoriasis: double-blind placebo-controlled randomised phase III trial. Lancet. 2006;367(9504):29–35.

    CAS  PubMed  Google Scholar 

  78. Gottlieb AB, Evans R, Li S, Dooley LT, Guzzo CA, Baker D, et al. Infliximab induction therapy for patients with severe plaque-type psoriasis: a randomized, double-blind, placebo-controlled trial. J Am Acad Dermatol. 2004;51(4):534–42.

    PubMed  Google Scholar 

  79. Reich K, Nestle FO, Papp K, Ortonne JP, Evans R, Guzzo C, et al. Infliximab induction and maintenance therapy for moderate-to-severe psoriasis: a phase III, multicentre, double-blind trial. Lancet. 2005;366(9494):1367–74.

    CAS  PubMed  Google Scholar 

  80. Menter A, Feldman SR, Weinstein GD, Papp K, Evans R, Guzzo C, et al. A randomized comparison of continuous vs. intermittent infliximab maintenance regimens over 1 year in the treatment of moderate-to-severe plaque psoriasis. J Am Acad Dermatol. 2007;56(1):31 e1–15.

    Google Scholar 

  81. Gordon KB, Langley RG, Leonardi C, Toth D, Menter MA, Kang S, et al. Clinical response to adalimumab treatment in patients with moderate to severe psoriasis: double-blind, randomized controlled trial and open-label extension study. J Am Acad Dermatol. 2006;55(4):598–606.

    PubMed  Google Scholar 

  82. Saurat JH, Stingl G, Dubertret L, Papp K, Langley RG, Ortonne JP, et al. Efficacy and safety results from the randomized controlled comparative study of adalimumab vs. methotrexate vs. placebo in patients with psoriasis (CHAMPION). Br J Dermatol. 2008;158(3):558–66.

    CAS  PubMed  Google Scholar 

  83. Leonardi CL, Kimball AB, Papp KA, Yeilding N, Guzzo C, Wang Y, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1). Lancet. 2008;371(9625):1665–74.

    CAS  PubMed  Google Scholar 

  84. Griffiths CE, Strober BE, van de Kerkhof P, Ho V, Fidelus-Gort R, Yeilding N, et al. Comparison of ustekinumab and etanercept for moderate-to-severe psoriasis. N Engl J Med. 2010;362(2):118–28.

    CAS  PubMed  Google Scholar 

  85. Leonardi C, Menter A, Hamilton T, Caro I, Xing B, Gottlieb AB. Efalizumab: results of a 3-year continuous dosing study for the long-term control of psoriasis. Br J Dermatol. 2008;158(5):1107–16.

    PubMed Central  CAS  PubMed  Google Scholar 

  86. Lebwohl M, Tyring SK, Hamilton TK, Toth D, Glazer S, Tawfik NH, et al. A novel targeted T-cell modulator, efalizumab, for plaque psoriasis. N Engl J Med. 2003;349(21):2004–13.

    CAS  PubMed  Google Scholar 

  87. Gordon KB, Papp KA, Hamilton TK, Walicke PA, Dummer W, Li N, et al. Efalizumab for patients with moderate to severe plaque psoriasis: a randomized controlled trial. JAMA. 2003;290(23):3073–80.

    CAS  PubMed  Google Scholar 

  88. Menter A, Gordon K, Carey W, Hamilton T, Glazer S, Caro I, et al. Efficacy and safety observed during 24 weeks of efalizumab therapy in patients with moderate to severe plaque psoriasis. Arch Dermatol. 2005;141(1):31–8.

    CAS  PubMed  Google Scholar 

  89. Leonardi CL, Papp KA, Gordon KB, Menter A, Feldman SR, Caro I, et al. Extended efalizumab therapy improves chronic plaque psoriasis: results from a randomized phase III trial. J Am Acad Dermatol. 2005;52(3 Pt 1):425–33.

    PubMed  Google Scholar 

  90. Gottlieb AB, Hamilton T, Caro I, Kwon P, Compton PG, Leonardi CL. Long-term continuous efalizumab therapy in patients with moderate to severe chronic plaque psoriasis: updated results from an ongoing trial. J Am Acad Dermatol. 2006;54(4 Suppl 1):S154–63.

    PubMed  Google Scholar 

  91. Papp KA, Bressinck R, Fretzin S, Goffe B, Kempers S, Gordon KB, et al. Safety of efalizumab in adults with chronic moderate to severe plaque psoriasis: a phase IIIb, randomized, controlled trial. Int J Dermatol. 2006;45(5):605–14.

    CAS  PubMed  Google Scholar 

  92. Tan CS, Koralnik IJ. Progressive multifocal leukoencephalopathy and other disorders caused by JC virus: clinical features and pathogenesis. Lancet Neurol. 2010;9(4):425–37.

    PubMed Central  CAS  PubMed  Google Scholar 

  93. Gottlieb AB, Chamian F, Masud S, Cardinale I, Abello MV, Lowes MA, et al. TNF inhibition rapidly down-regulates multiple proinflammatory pathways in psoriasis plaques. J Immunol. 2005;175(4):2721–9.

    CAS  PubMed  Google Scholar 

  94. Zaba LC, Cardinale I, Gilleaudeau P, Sullivan-Whalen M, Suarez-Farinas M, Fuentes-Duculan J, et al. Amelioration of epidermal hyperplasia by TNF inhibition is associated with reduced Th17 responses. J Exp Med. 2007;204(13):3183–94.

    PubMed Central  CAS  PubMed  Google Scholar 

  95. Zaba LC, Suarez-Farinas M, Fuentes-Duculan J, Nograles KE, Guttman-Yassky E, Cardinale I, et al. Effective treatment of psoriasis with etanercept is linked to suppression of IL-17 signaling, not immediate response TNF genes. J Allergy Clin Immunol. 2009;124(5):1022–10 e1-395.

    PubMed Central  CAS  PubMed  Google Scholar 

  96. Sivamani RK, Goodarzi H, Garcia MS, Raychaudhuri SP, Wehrli LN, Ono Y, et al. Biologic therapies in the treatment of psoriasis: a comprehensive evidence-based basic science and clinical review and a practical guide to tuberculosis monitoring. Clin Rev Allergy Immunol. 2013;44(2):121–40.

    CAS  PubMed  Google Scholar 

  97. Papp KA, Poulin Y, Bissonnette R, Bourcier M, Toth D, Rosoph L, et al. Assessment of the long-term safety and effectiveness of etanercept for the treatment of psoriasis in an adult population. J Am Acad Dermatol. 2012;66(2):e33–45.

    CAS  PubMed  Google Scholar 

  98. Papp KA, Griffiths CE, Gordon K, Lebwohl M, Szapary PO, Wasfi Y, et al. Long-term safety of ustekinumab in patients with moderate-to-severe psoriasis: final results from 5 years of follow-up. Br J Dermatol. 2013;168(4):844–54.

    CAS  PubMed  Google Scholar 

  99. Merck. A Study to evaluate the efficacy and safety/tolerability of subcutaneous SCH 900222/MK-3222 in participants with moderate-to-severe chronic plaque psoriasis (P07771/MK-3222-011). Available from: http://clinicaltrials.gov/ct2/show/NCT01729754. Accessed 26 Mar 2014.

  100. Papp K. Dose-dependent improvement in chronic plaque psoriasis following treatment with anti-IL-23p19 humanized monoclonal antibody (MK-3222). Presented at American Academy of Dermatology conference, Miami, 2013.

    Google Scholar 

  101. Jannsenn Inc. A study to evaluate CNTO 1959 in the treatment of patients with moderate to severe plaque-type psoriasis (X-PLORE). Available from: http://clinicaltrials.gov/ct2/show/NCT01483599. Accessed 26 Mar 2014

  102. Callis Duffin K. A phase 2 multicenter, randomized, placebo- and active-comparator controlled, dose-ranging trial to evaluate Guselkumab for the treatment of patients with moderate to severe plaque-type psoriasis (X-PLORE). Presented at American Academy of Dermatology conference, Denver, 2014.

    Google Scholar 

  103. Boehringer Ingelheim. BI 655066 Dose ranging in psoriasis, active comparator Ustekinumab. Available from: http://clinicaltrials.gov/ct2/show/NCT02054481. Accessed 26 Mar 2014.

  104. Papp KA, Leonardi C, Menter A, Ortonne JP, Krueger JG, Kricorian G, et al. Brodalumab, an anti-interleukin-17-receptor antibody for psoriasis. N Engl J Med. 2012;366(13):1181–9.

    CAS  PubMed  Google Scholar 

  105. Leonardi C, Matheson R, Zachariae C, Cameron G, Li L, Edson-Heredia E, et al. Anti-interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis. N Engl J Med. 2012;366(13):1190–9.

    CAS  PubMed  Google Scholar 

  106. Papp KA, Langley RG, Sigurgeirsson B, Abe M, Baker DR, Konno P, et al. Efficacy and safety of secukinumab in the treatment of moderate-to-severe plaque psoriasis: a randomized, double-blind, placebo-controlled phase II dose-ranging study. Br J Dermatol. 2013;168(2):412–21.

    CAS  PubMed  Google Scholar 

  107. Papp KA, Kaufmann R, Thaci D, Hu C, Sutherland D, Rohane P. Efficacy and safety of apremilast in subjects with moderate to severe plaque psoriasis: results from a phase II, multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison study. J Eur Acad Dermatol Venereol. 2013;27(3):e376–83.

    CAS  PubMed  Google Scholar 

  108. Papp K, Cather JC, Rosoph L, Sofen H, Langley RG, Matheson RT, et al. Efficacy of apremilast in the treatment of moderate to severe psoriasis: a randomised controlled trial. Lancet. 2012;380(9843):738–46.

    CAS  PubMed  Google Scholar 

  109. Boy MG, Wang C, Wilkinson BE, Chow VF, Clucas AT, Krueger JG, et al. Double-blind, placebo-controlled, dose-escalation study to evaluate the pharmacologic effect of CP-690,550 in patients with psoriasis. J Invest Dermatol. 2009;129(9):2299–302.

    CAS  PubMed  Google Scholar 

  110. Papp KA, Menter A, Strober B, Langley RG, Buonanno M, Wolk R, et al. Efficacy and safety of tofacitinib, an oral Janus kinase inhibitor, in the treatment of psoriasis: a Phase 2b randomized placebo-controlled dose-ranging study. Br J Dermatol. 2012;167(3):668–77.

    CAS  PubMed  Google Scholar 

  111. Ports WC, Khan S, Lan S, Lamba M, Bolduc C, Bissonnette R, et al. A randomized phase 2a efficacy and safety trial of the topical Janus kinase inhibitor tofacitinib in the treatment of chronic plaque psoriasis. Br J Dermatol. 2013;169(1):137–45.

    PubMed Central  CAS  PubMed  Google Scholar 

  112. Krueger JG, Fretzin S, Suarez-Farinas M, Haslett PA, Phipps KM, Cameron GS, et al. IL-17A is essential for cell activation and inflammatory gene circuits in subjects with psoriasis. J Allergy Clin Immunol. 2012;130(1):145–54 e9.

    PubMed Central  CAS  PubMed  Google Scholar 

  113. National Institute for Health and Care Excellence. Costing statement: Ustekinumab for the treatment of adults with moderate to severe psoriasis. 2009. Available from: http://www.nice.org.uk/guidance/ta180/resources/ta180-psoriasis-ustekinumab-costing-statement2

  114. Vincent FB, Morand EF, Murphy K, Mackay F, Mariette X, Marcelli C. Antidrug antibodies (ADAb) to tumour necrosis factor (TNF)-specific neutralising agents in chronic inflammatory diseases: a real issue, a clinical perspective. Ann Rheum Dis. 2013;72(2):165–78.

    CAS  PubMed  Google Scholar 

  115. Sathish JG, Sethu S, Bielsky MC, de Haan L, French NS, Govindappa K, et al. Challenges and approaches for the development of safer immunomodulatory biologics. Nat Rev Drug Discov. 2013;12(4):306–24.

    CAS  PubMed  Google Scholar 

  116. Garcia-Perez ME, Stevanovic T, Poubelle PE. New therapies under development for psoriasis treatment. Curr Opin Pediatr. 2013;25(4):480–7.

    PubMed  Google Scholar 

  117. Garrod AE. About Alkaptonuria. Med Chir Trans. 1902;85:69–78.

    PubMed Central  CAS  PubMed  Google Scholar 

  118. Alving AS, Carson PE, Flanagan CL, Ickes CE. Enzymatic deficiency in primaquine-sensitive erythrocytes. Science. 1956;124(3220):484–5.

    CAS  PubMed  Google Scholar 

  119. Cooper DY, Levin S, Narasimhulu S, Rosenthal O. Photochemical action spectrum of the terminal oxidase of mixed function oxidase systems. Science. 1965;147(3656):400–2.

    CAS  PubMed  Google Scholar 

  120. Vogel F. Moderne problem der humangenetik. Ergeb Inn Med U Kinderheilk. 1959;12:52–125.

    Google Scholar 

  121. Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, et al. The sequence of the human genome. Science. 2001;291(5507):1304–51.

    CAS  PubMed  Google Scholar 

  122. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, et al. Initial sequencing and analysis of the human genome. Nature. 2001;409(6822):860–921.

    CAS  PubMed  Google Scholar 

  123. Sherry ST, Ward MH, Kholodov M, Baker J, Phan L, Smigielski EM, et al. dbSNP: the NCBI database of genetic variation. Nucleic Acids Res. 2001;29(1):308–11.

    PubMed Central  CAS  PubMed  Google Scholar 

  124. Altshuler DM, Gibbs RA, Peltonen L, Dermitzakis E, Schaffner SF, Yu F, et al. Integrating common and rare genetic variation in diverse human populations. Nature. 2010;467(7311):52–8.

    CAS  PubMed  Google Scholar 

  125. Abecasis GR, Auton A, Brooks LD, DePristo MA, Durbin RM, Handsaker RE, et al. An integrated map of genetic variation from 1,092 human genomes. Nature. 2012;491(7422):56–65.

    PubMed  Google Scholar 

  126. Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69(3):89–95.

    Google Scholar 

  127. Villanova F, Di Meglio P, Nestle FO. Biomarkers in psoriasis and psoriatic arthritis. Ann Rheum Dis. 2013;72 Suppl 2:ii104–10.

    CAS  PubMed  Google Scholar 

  128. Soreide K. Receiver-operating characteristic curve analysis in diagnostic, prognostic and predictive biomarker research. J Clin Pathol. 2009;62(1):1–5.

    PubMed  Google Scholar 

  129. Hudis CA. Trastuzumab–mechanism of action and use in clinical practice. N Engl J Med. 2007;357(1):39–51.

    CAS  PubMed  Google Scholar 

  130. Sanger F, Coulson AR. A rapid method for determining sequences in DNA by primed synthesis with DNA polymerase. J Mol Biol. 1975;94(3):441–8.

    CAS  PubMed  Google Scholar 

  131. Schadt EE, Turner S, Kasarskis A. A window into third-generation sequencing. Hum Mol Genet. 2010;19(R2):R227–40.

    CAS  PubMed  Google Scholar 

  132. Ku CS, Naidoo N, Wu M, Soong R. Studying the epigenome using next generation sequencing. J Med Genet. 2011;48(11):721–30.

    CAS  PubMed  Google Scholar 

  133. Wang Z, Gerstein M, Snyder M. RNA-Seq: a revolutionary tool for transcriptomics. Nat Rev Genet. 2009;10(1):57–63.

    PubMed Central  CAS  PubMed  Google Scholar 

  134. Tian S, Krueger JG, Li K, Jabbari A, Brodmerkel C, Lowes MA, et al. Meta-analysis derived (MAD) transcriptome of psoriasis defines the “core” pathogenesis of disease. PLoS One. 2012;7(9):e44274.

    PubMed Central  CAS  PubMed  Google Scholar 

  135. Jabbari A, Suarez-Farinas M, Dewell S, Krueger JG. Transcriptional profiling of psoriasis using RNA-seq reveals previously unidentified differentially expressed genes. J Invest Dermatol. 2012;132(1):246–9.

    PubMed Central  CAS  PubMed  Google Scholar 

  136. Suarez-Farinas M, Lowes MA, Zaba LC, Krueger JG. Evaluation of the psoriasis transcriptome across different studies by gene set enrichment analysis (GSEA). PLoS One. 2010;5(4):e10247.

    PubMed Central  PubMed  Google Scholar 

  137. Swindell WR, Johnston A, Voorhees JJ, Elder JT, Gudjonsson JE. Dissecting the psoriasis transcriptome: inflammatory- and cytokine-driven gene expression in lesions from 163 patients. BMC Genomics. 2013;14:527.

    PubMed Central  CAS  PubMed  Google Scholar 

  138. Roberson ED, Liu Y, Ryan C, Joyce CE, Duan S, Cao L, et al. A subset of methylated CpG sites differentiate psoriatic from normal skin. J Invest Dermatol. 2012;132(3 Pt 1):583–92.

    PubMed Central  CAS  PubMed  Google Scholar 

  139. Villanova F, Di Meglio P, Inokuma M, Aghaeepour N, Perucha E, Mollon J, et al. Integration of lyoplate based flow cytometry and computational analysis for standardized immunological biomarker discovery. PLoS One. 2013;8(7):e65485.

    PubMed Central  CAS  PubMed  Google Scholar 

  140. Bendall SC, Nolan GP, Roederer M, Chattopadhyay PK. A deep profiler’s guide to cytometry. Trends Immunol. 2012;33(7):323–32.

    PubMed Central  CAS  PubMed  Google Scholar 

  141. Bendall SC, Simonds EF, Qiu P, el Amir AD, Krutzik PO, Finck R, et al. Single-cell mass cytometry of differential immune and drug responses across a human hematopoietic continuum. Science. 2011;332(6030):687–96.

    PubMed Central  CAS  PubMed  Google Scholar 

  142. Newell EW, Sigal N, Bendall SC, Nolan GP, Davis MM. Cytometry by time-of-flight shows combinatorial cytokine expression and virus-specific cell niches within a continuum of CD8+ T cell phenotypes. Immunity. 2012;36(1):142–52.

    PubMed Central  CAS  PubMed  Google Scholar 

  143. Han A, Newell EW, Glanville J, Fernandez-Becker N, Khosla C, Chien YH, et al. Dietary gluten triggers concomitant activation of CD4+ and CD8+ alphabeta T cells and gammadelta T cells in celiac disease. Proc Natl Acad Sci U S A. 2013;110(32):13073–8.

    PubMed Central  CAS  PubMed  Google Scholar 

  144. Covey TM, Cesano A, Parkinson DR. Single-cell network profiling (SCNP) by flow cytometry in autoimmune disease. Autoimmunity. 2010;43(7):550–9.

    PubMed  Google Scholar 

  145. Putri SP, Yamamoto S, Tsugawa H, Fukusaki E. Current metabolomics: technological advances. J Biosci Bioeng. 2013;116(1):9–16.

    CAS  PubMed  Google Scholar 

  146. Reisdorph N, Wechsler ME. Utilizing metabolomics to distinguish asthma phenotypes: strategies and clinical implications. Allergy. 2013;68(8):959–62.

    CAS  PubMed  Google Scholar 

  147. Berger B, Peng J, Singh M. Computational solutions for omics data. Nat Rev Genet. 2013;14(5):333–46.

    PubMed Central  CAS  PubMed  Google Scholar 

  148. Suarez-Farinas M, Fuentes-Duculan J, Lowes MA, Krueger JG. Resolved psoriasis lesions retain expression of a subset of disease-related genes. J Invest Dermatol. 2011;131(2):391–400.

    PubMed Central  CAS  PubMed  Google Scholar 

  149. Ainali C, Valeyev N, Perera G, Williams A, Gudjonsson JE, Ouzounis CA, et al. Transcriptome classification reveals molecular subtypes in psoriasis. BMC Genomics. 2012;13:472.

    PubMed Central  CAS  PubMed  Google Scholar 

  150. Perera GK, Ainali C, Semenova E, Hundhausen C, Barinaga G, Kassen D, et al. Integrative biology approach identifies cytokine targeting strategies for psoriasis. Sci Transl Med. 2014;6(223):223ra22.

    PubMed  Google Scholar 

  151. Valeyev NV, Hundhausen C, Umezawa Y, Kotov NV, Williams G, Clop A, et al. A systems model for immune cell interactions unravels the mechanism of inflammation in human skin. PLoS Comput Biol. 2010;6(12):e1001024.

    PubMed Central  PubMed  Google Scholar 

  152. Armstrong AW, Robertson AD, Wu J, Schupp C, Lebwohl MG. Undertreatment, treatment trends, and treatment dissatisfaction among patients with psoriasis and psoriatic arthritis in the United States: findings from the National Psoriasis Foundation surveys, 2003–2011. JAMA Dermatol. 2013;149(10):1180–5.

    PubMed  Google Scholar 

  153. Ho PY, Barton A, Worthington J, Plant D, Griffiths CE, Young HS, et al. Investigating the role of the HLA-Cw*06 and HLA-DRB1 genes in susceptibility to psoriatic arthritis: comparison with psoriasis and undifferentiated inflammatory arthritis. Ann Rheum Dis. 2008;67(5):677–82.

    PubMed Central  CAS  PubMed  Google Scholar 

  154. Piruzian E, Bruskin S, Ishkin A, Abdeev R, Moshkovskii S, Melnik S, et al. Integrated network analysis of transcriptomic and proteomic data in psoriasis. BMC Syst Biol. 2010;4:41.

    PubMed Central  PubMed  Google Scholar 

  155. Yamamoto T, Nishioka K. Alteration of the expression of Bcl-2, Bcl-x, Bax, Fas, and Fas ligand in the involved skin of psoriasis vulgaris following topical anthralin therapy. Skin Pharmacol Appl Skin Physiol. 2003;16(1):50–8.

    CAS  PubMed  Google Scholar 

  156. Kokolakis G, Giannikaki E, Stathopoulos E, Avramidis G, Tosca AD, Kruger-Krasagakis S. Infliximab restores the balance between pro- and anti-apoptotic proteins in regressing psoriatic lesions. Br J Dermatol. 2012;166(3):491–7.

    CAS  PubMed  Google Scholar 

  157. Rashmi R, Rao KS, Basavaraj KH. A comprehensive review of biomarkers in psoriasis. Clin Exp Dermatol. 2009;34(6):658–63.

    CAS  PubMed  Google Scholar 

  158. Arican O, Aral M, Sasmaz S, Ciragil P. Serum levels of TNF-alpha, IFN-gamma, IL-6, IL-8, IL-12, IL-17, and IL-18 in patients with active psoriasis and correlation with disease severity. Mediators Inflamm. 2005;2005(5):273–9.

    PubMed Central  PubMed  Google Scholar 

  159. Suarez-Farinas M, Li K, Fuentes-Duculan J, Hayden K, Brodmerkel C, Krueger JG. Expanding the psoriasis disease profile: interrogation of the skin and serum of patients with moderate-to-severe psoriasis. J Invest Dermatol. 2012;132(11):2552–64.

    PubMed Central  CAS  PubMed  Google Scholar 

  160. Meephansan J, Ruchusatsawat K, Sindhupak W, Thorner PS, Wongpiyabovorn J. Effect of methotrexate on serum levels of IL-22 in patients with psoriasis. Eur J Dermatol. 2011;21(4):501–4.

    CAS  PubMed  Google Scholar 

  161. Michalak-Stoma A, Bartosinska J, Kowal M, Juszkiewicz-Borowiec M, Gerkowicz A, Chodorowska G. Serum levels of selected Th17 and Th22 cytokines in psoriatic patients. Dis Markers. 2013;35(6):625–31.

    PubMed Central  PubMed  Google Scholar 

  162. Di Meglio P, Nestle FO. The role of IL-23 in the immunopathogenesis of psoriasis. F1000 Biol Rep. 2010;2:40.

    PubMed Central  PubMed  Google Scholar 

  163. Tonel G, Conrad C, Laggner U, Di Meglio P, Grys K, McClanahan TK, et al. Cutting edge: A critical functional role for IL-23 in psoriasis. J Immunol. 2010;185(10):5688–91.

    PubMed Central  CAS  PubMed  Google Scholar 

  164. El-Moaty Zaher HA, El-Komy MH, Hegazy RA, Mohamed E, Khashab HA, Ahmed HH. Assessment of interleukin-17 and vitamin D serum levels in psoriatic patients. J Am Acad Dermatol. 2013;69(5):840–2.

    PubMed  Google Scholar 

  165. Choe YB, Hwang YJ, Hahn HJ, Jung JW, Jung HJ, Lee YW, et al. A comparison of serum inflammatory cytokines according to phenotype in patients with psoriasis. Br J Dermatol. 2012;167(4):762–7.

    CAS  PubMed  Google Scholar 

  166. Cheuk S, Wiken M, Blomqvist L, Nylen S, Talme T, Stahle M, et al. Epidermal Th22 and Tc17 cells form a localized disease memory in clinically healed psoriasis. J Immunol. 2014;192:3111–20.

    PubMed Central  CAS  PubMed  Google Scholar 

  167. Benham H, Norris P, Goodall J, Wechalekar MD, FitzGerald O, Szentpetery A, et al. Th17 and Th22 cells in psoriatic arthritis and psoriasis. Arthritis Res Ther. 2013;15(5):R136.

    PubMed Central  PubMed  Google Scholar 

  168. Rocha-Pereira P, Santos-Silva A, Rebelo I, Figueiredo A, Quintanilha A, Teixeira F. The inflammatory response in mild and in severe psoriasis. Br J Dermatol. 2004;150(5):917–28.

    CAS  PubMed  Google Scholar 

  169. Gupta M, Chari S, Borkar M, Chandankhede M. Dyslipidemia and oxidative stress in patients of psoriasis. Biomed Res. 2011;22(2):221–4.

    CAS  Google Scholar 

  170. Tekin NS, Tekin IO, Barut F, Sipahi EY. Accumulation of oxidized low-density lipoprotein in psoriatic skin and changes of plasma lipid levels in psoriatic patients. Mediators Inflamm. 2007;2007:78454.

    PubMed Central  PubMed  Google Scholar 

  171. Haider AS, Lowes MA, Suarez-Farinas M, Zaba LC, Cardinale I, Khatcherian A, et al. Identification of cellular pathways of “type 1,” Th17 T cells, and TNF- and inducible nitric oxide synthase-producing dendritic cells in autoimmune inflammation through pharmacogenomic study of cyclosporine A in psoriasis. J Immunol. 2008;180(3):1913–20.

    CAS  PubMed  Google Scholar 

  172. Johnson-Huang LM, Suarez-Farinas M, Sullivan-Whalen M, Gilleaudeau P, Krueger JG, Lowes MA. Effective narrow-band UVB radiation therapy suppresses the IL-23/IL-17 axis in normalized psoriasis plaques. J Invest Dermatol. 2010;130(11):2654–63.

    PubMed Central  CAS  PubMed  Google Scholar 

  173. Suarez-Farinas M, Shah KR, Haider AS, Krueger JG, Lowes MA. Personalized medicine in psoriasis: developing a genomic classifier to predict histological response to Alefacept. BMC Dermatol. 2010;10:1.

    PubMed Central  PubMed  Google Scholar 

  174. Richetta AG, Mattozzi C, Salvi M, Giancristoforo S, Cantisani C, D’Epiro S, et al. Downregulation of circulating CD4+ CD25(bright) Foxp3+ T cells by cyclosporine therapy and correlation with clinical response in psoriasis patients: report of three cases. Int J Dermatol. 2013;52(11):1437–9.

    CAS  PubMed  Google Scholar 

  175. Jokai H, Szakonyi J, Kontar O, Barna G, Inotai D, Karpati S, et al. Cutaneous lymphocyte-associated antigen as a novel predictive marker of TNF-alpha inhibitor biological therapy in psoriasis. Exp Dermatol. 2013;22(3):221–3.

    CAS  PubMed  Google Scholar 

  176. Warren RB, Smith RL, Campalani E, Eyre S, Smith CH, Barker JN, et al. Genetic variation in efflux transporters influences outcome to methotrexate therapy in patients with psoriasis. J Invest Dermatol. 2008;128(8):1925–9.

    CAS  PubMed  Google Scholar 

  177. Tejasvi T, Stuart PE, Chandran V, Voorhees JJ, Gladman DD, Rahman P, et al. TNFAIP3 gene polymorphisms are associated with response to TNF blockade in psoriasis. J Invest Dermatol. 2012;132(3 Pt 1):593–600.

    PubMed Central  CAS  PubMed  Google Scholar 

  178. Talamonti M, Botti E, Galluzzo M, Teoli M, Spallone G, Bavetta M, et al. Pharmacogenetics of psoriasis: HLA-Cw6 but not LCE3B/3C deletion nor TNFAIP3 polymorphism predisposes to clinical response to interleukin 12/23 blocker ustekinumab. Br J Dermatol. 2013;169(2):458–63.

    CAS  PubMed  Google Scholar 

  179. BSTOP. Biomarkers of Systemic Treatment Outcomes in Psoriasis (BSTOP) study. Available from: http://www.kcl.ac.uk/medicine/research/divisions/gmm/departments/dermatology/Research/stru/groups/bstop/index.aspx. Accessed 26 Mar 2014.

  180. PSORT. Psoriasis Stratification to Optimise Relevant Therapy. Available from: www.psort.org.uk. Accessed 26 Mar 2014.

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Acknowledgments

We are in debt to psoriasis patients and healthy volunteers for their courage, trust, and generosity in donating clinical specimens to make psoriasis research possible. We thank FON laboratory members for their contribution over the years to the work cited in this chapter. We thank Hemawtee Sreeneebus and Thomas Walters for their help with Fig. 6.1. We acknowledge support by the following grant bodies: Wellcome Trust Programme GR078173MA (FON) and National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. FON has been a consultant for companies producing targeted therapies for treatment of patients with psoriasis. The other authors state no conflict of interest.

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  1. St John’s Institute of Dermatology, King’s College London, London, SE1 9RT, UK

    Federica Villanova PhD & Frank O. Nestle MD

  2. Molecular Immunology, MRC NIMR, London, NW7 1AA, UK

    Paola Di Meglio MPharm, PhD

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  1. Department of Dermatology and Allergy, Center of Translational Medicine, University of Bonn, Bonn, Germany

    Thomas Bieber

  2. St. John's Institute of Dermatology, London, United Kingdom

    Frank Nestle

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Villanova, F., Di Meglio, P., Nestle, F.O. (2015). Targeted Therapies and Biomarkers for Personalized Treatment of Psoriasis. In: Bieber, T., Nestle, F. (eds) Personalized Treatment Options in Dermatology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-45840-2_6

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