Search for new molecular targets for anticytokine therapy of patients, suffering from the immune dependent skin disease — psoriasis


The authors describe the results of a study aimed at searching for new molecular targets for anticytokine therapy of patients with psoriasis. The authors examined 26 patients with psoriasis who were treated with such immune biologic substances as infliximab, ustekinumab, adalimumab and 10 healthy volunteers. They performed a quality and quantity analysis of the spectrum of protein molecules of cytokines (L-4, IL-6, IL-17, TNF-α and IL-20, IL-22, IL-31, IL-12, IL-11, IL-18) аs well as VEGF and ICAM-1 molecules in patients receiving the therapy with immune biologic substances before and after treatment using the methodology of the immune enzyme analysis and xMAP multiplex technology. The authors studied the correlation between the level of cytokine expression, on the one hand, and the occurrence and limitation of the disease, on the other hand. The obtained data are sufficient to conclude that the spectrum of molecules of IL6, IL20, IL22 anti-inflammatory cytokines аs well as VEGF and ICAM-1 molecules, for which pathogenic importance in case of psoriasis was revealed as a result of the study , may serve as a potential (new, additional) molecular target for anticytokine therapy of patients suffering with such an immune-dependent skin disease as psoriasis.

Full Text

Поиск новых молекулярных мишеней для антицитокиновой терапии больных иммунозависимым заболеванием кожи — псориазом


  1. Chien A.L., Elder J.T., Ellis C.N. Ustekinumab: A new option in psoriasis therapy. Drugs. 2009; 69: 1141—1152.
  2. Gottlieb A., Korman N.J., Gordon K.B., Feldman S.R., Lebwohl M., Koo J.Y., Van Voorhees A.S., Elmets C.A., Leonardi C.L., Beutner K.R., Bhushan R., Menter A. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 2. Psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics. J Am Acad Dermatol. 2008; 58: 851—864.
  3. Liu Y., Helms C., Liao W., Zaba L.C., Duan S., Gardner J., Wise C., Miner A., Malloy M.J., Pullinger C.R., Kane J.P., Saccone S., Worthington J., Bruce I., Kwok P.Y., Menter A., Krueger J., Barton A., Saccone N.L., Bowcock A.M. A genome-wide association study of psoriasis and psoriatic arthritis identifies new disease loci. PLoS Genet. 2008; 4: e1000041.
  4. Nair R.P., Stuart P.E., Nistor I., Hiremagalore R., Chia N.V., Jenisch S., Weichenthal M., Abecasis G.R., Lim H.W., Christophers E., Voorhees J.J., Elder J.T. Sequence and haplotype analysis supports HLA-C as the psoriasis susceptibility 1 gene. Am J Hum Genet. 2006; 78: 827—851.
  5. Nickoloff B.J., Nestle F.O. Recent insights into the immunopathogenesis of psoriasis provide new therapeutic opportunities. J Clin Invest. 2004; 113: 1664—1675.
  6. Rahman P., Elder J.T. Genetic epidemiology of psoriasis and psoriatic arthritis. Ann Rheum Dis. 2005; 64 Suppl 2: ii37—39; discussion ii40—31.
  7. Teraoka Y., Naruse T.K., Oka A., Matsuzawa Y., Shiina T., lizuka M., Iwashita K., Ozawa A., Inoko H. Genetic polymorphisms in the cell growth regulated gene, SC1 telomeric of the HLA-C gene and lack of association of psoriasis vulgaris. Tissue Antigens. 2000; 55: 206—211.
  8. Беляев Г.М., Рыжко П.П. Псориаз. Псориартрическая артропатия. МЕДпресс-информ, 2005; 1—272.
  9. Рахимова О.Ю., Виноградов Ю.А., Юрков М.Ю., Савицкий А.В., Митрофанова И.П. Псориаз и болезнь Крона. Клин. мед. 2008; 7: 70—72.
  10. Gottlieb A.B., Matheson R.T., Lowe N., Krueger G.G., Kang S., Goffe B.S., Gaspari A.A., Ling M., Weinstein G.D., Nayak A., Gordon K.B., Zitnik R. A randomized trial of etanercept as monotherapy for psoriasis. Arch Dermatol. 2003; 139: 1627—1632; discussion 1632.
  11. Кубанова А.А., Кисина В.И. Рациональная фармакотерапия заболеваний кожи и инфекций, передаваемых половым путем. М.: Литтерра, 2005; 365—378.
  12. Menter A., Tyring S.K., Gordon K., Kimball A.B., Leonardi C.L., Langley R.G., Strober B.E., Kaul M., Gu Y., Okun M. Adalimumab therapy for moderate to severe psoriasis: a randomized, controlled phase III trial. J Amer Acad Dermatol. 2008; 58: 106—115.
  13. Gordon K.B., Langley R.G., Leonardi C., Toth D., Menter M.A., Kang S., Heffernan M., Miller B., Hamlin R., Lim L. Clinical response to adalimumab treatment in patients with moderate to severe psoriasis: double-blind, randomized controlled trial and open-label extension study. J Amer Acad Dermatol. 2006; 55: 598—606.
  14. Sonkoly E., Stahle M., Pivarcsi A. MicroRNAs and immunity: novel players in the regulation of normal immune function and inflammation. Semin Cancer Biol. 2008; 18: 131—140.
  15. Wittig B. Drug evaluation: CNTO-1275, a mAb against IL-12/IL-23p40 for the potential treatment of inflammatory diseases. Current opinion in investigational drugs (London, England: 2000). 2007; 8: 947.
  16. Каратеев Д.Е. Вопросы иммуногенности биологических препаратов: теория и практика. Соврем. ревматол. 2009; 67—72.
  17. Mizutani H., Ohmoto Y., Mizutani T., Murata M., Shimizu M. Role of increased production of monocytes TNF-[alpha], IL-1 [beta] and IL-6 in psoriasis: relation to focal infection, disease activity and responses to treatments. J dermatol science. 1997; 14: 145—153.
  18. Prens E., Hegmans J., Lien R., Debets R., Troost R., Van Joost T., Benner R. Increased expression of interleukin-4 receptors on psoriatic epidermal cells. Amer J pathol. 1996; 148: 1493.
  19. Trepicchio W.L., Ozawa M., Walters I.B., Kikuchi T., Gilleaudeau P., Bliss J.L., Schwertschlag U., Dorner A.J., Krueger J.G. Interleukin-11 therapy selectively downregulates type I cytokine proinflammatory pathways in psoriasis lesions. J Clin Invest. 1999; 104: 1527—1537.
  20. Oestreicher J., Walters I., Kikuchi T., Gilleaudeau P., Surette J., Schwertschlag U., Dorner A., Krueger J., Trepicchio W. Molecular classification of psoriasis disease-associated genes through pharmacogenomic expression profiling. Pharmacogen J 2001; 1: 272—287.
  21. Yawalkar N., Karlen S., Hunger R., Brand C.U., Braathen L.R. Expression of interleukin-12 is increased in psoriatic skin. J Invest Dermatol 1998; 111: 1053—1057.
  22. Nograles K.E., Krueger J.G. Anti-cytokine therapies for psoriasis. Exp Cell Res. 2011.
  23. Albanesi C., Scarponi C., Cavani A., Federici M., Nasorri F., Girolomoni G. Interleukin-17 is produced by both Th1 and Th2 lymphocytes, and modulates interferon- -and interleukin-4-induced activation of human keratinocytes. J Invest Derm. 2000; 115: 81—87.
  24. Koga C., Kabashima K., Shiraishi N., Kobayashi M., Tokura Y. Possible pathogenic role of Th17 cells for atopic dermatitis. J Invest Derm. 2008; 128: 2625—2630.
  25. Ohta Y., Hamada Y., Katsuoka K. Expression of IL-18 in psoriasis. Arch Derm Res. 2001; 293: 334—342.
  26. Rich B.E., Kupper T.S. Cytokines: IL-20--a new effector in skin inflammation. Curr Biol. 2001; 11: R531—R534.
  27. Boniface K., Bernard F.X., Garcia M., Gurney A.L., Lecron J.C., Morel F. IL-22 inhibits epidermal differentiation and induces proinflammatory gene expression and migration of human keratinocytes. J Immunol. 2005; 174: 3695.
  28. Canavese M., Altruda F., Ruzicka T., Schauber J. Vascular endothelial growth factor (VEGF) in the pathogenesis of psoriasis--a possible target for novel therapies? J Derm Sci. 2010; 58: 171—176.
  29. Das P., De Boer O., Visser A., Verhagen C., Bos J., Pals S. Differential expression of ICAM-1, E-selectin and VCAM-1 by endothelial cells in psoriasis and contact dermatitis. Acta dermato-venereologica. Supplementum. 1994; 186: 21.
  30. Terajima S., Higaki M., Igarashi Y., Nogita T., Kawashima M. An important role of tumor necrosis factor- in the induction of adhesion molecules in psoriasis. Arch Derm Res. 1998; 290: 246—252.
  31. Cabrijan L., Batinac T., Lenkovic M., Gruber F. The distinction between lesional and non-lesional skin in psoriasis vulgaris through expression of adhesion molecules ICAM-1 and VCAM-1. Medical hypotheses. 2009; 72: 327—329.
  32. Фриго Н.В., Кубанов А.А., Знаменская Л.В. Молекулярные маркеры в прогнозировании клинической эффективности имфликсимаба у больных псориазом. Вестн. дерматол. и венерол. 2010; 1: 57—66.
  33. Gudjonsson J.E., Johnston A., Dyson M., Valdimarsson H., Elder J.T. Mouse models of psoriasis. J Investi Derm. 2007; 127: 1292—1308.
  34. Sano S., Chan K.S., Carbajal S., Clifford J., Peavey M., Kiguchi K., Itami S., Nickoloff B.J., Digiovanni J. Stat3 links activated keratinocytes and immunocytes required for development of psoriasis in a novel transgenic mouse model. Nature medic. 2004; 11: 43—49.



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