ГЕНЕТИЧЕСКИЕ ФАКТОРЫ В ИММУНОПАТОГЕНЕЗЕ ПСОРИАЗА И ПСОРИАТИЧЕСКОГО АРТРИТА
Аннотация
Существует генетически обусловленная предрасположенность к развитию псориаза (ПС) и псориатического артрита (ПсА), в которой существенное значение имеют гены цитокинов. Идентификация полиморфных вариантов генов иммунного ответа (генов цитокинов и их рецепторов) – перспективное направление в изучении генетических факторов риска развития воспаления в коже и суставах при ПС и ПсА. В иммунопатогенезе псориаза и псориатического артрита ведущими являются иммунные нарушения, характеризующиеся девиацией цитокинового профиля по Th1-типу (IL- 2, IFNγ, TNFα). В обзоре проведен анализ данных литературы, раскрывающих роль полиморфизма генов цитокинов в ассоциации с характером течения ПС и ПсА. Поиск генетических маркеров риска развития ПС и ПсА является важным шагом персонализированного подхода к прогнозу течения заболевания и формированию профилактических мероприятий с целью предупреждения прогрессирования патологического процесса.
Об авторах
М. В. Смольникова
ФГБУ «Научно-исследовательский институт медицинских проблем Севера» СО РАМН, г. Красноярск
Россия
Россия
к.б.н., ведущий научный сотрудник, лаборатория клеточно-молекулярной физиологии и патологии ФГБУ «Научно-исследовательский институт медицинских проблем Севера» СО РАМН
С. В. Смирнова
ФГБУ «Научно-исследовательский институт медицинских проблем Севера» СО РАМН, г. Красноярск
Россия
Россия
д.м.н., профессор, заместитель директора по научной работе, руководитель отдела клинической иммунологии и клеточных технологий, ФГБУ «Научно-исследовательский институт медицинских проблем Севера» СО РАМН
Список литературы
1. Dovzhanskiy S.I., Pinson I.Yа. Geneticheskie i immunnye faktory v patogeneze psoriaza [Genetic and immune factors in the pathogenesis of psoriasis]. Rossiyskiy zhurnal kozhnykh i venericheskikh bolezney – Russian Journal of Skin and Venereal Diseases, 2006, no. 1, pp. 14-19.
2. Konenkov V.I., Smolnikova M.V. Strukturnye osnovy i funktsional`naya znachimost` allel`nogo polimorfizma genov tsitokinov cheloveka i ikh retseptorov [The structure bases and functional value of the allelic polymorphism of the cytokine’s genes and genes of their receptors]. Meditsinskaya immunologiya – Medical Immunology, 2003, vol. 5, no. 1-2, pp. 11-28.
3. Pinegin B.V., Ivanov O.L., Pinegin V.B. Rol` kletok immunnoy sistemy i tsitokinov v razvitii psoriaza [Role of cells of immune system and cytokines in psoriasis development]. Immunologiya – Immunology, 2012, no. 4, pp. 213- 219.
4. Smolnikova M.V., Smirnova S.V. Assotsiatsiya polimorfnykh markerov genov IL4 (S-590T) i IL10 (S-597A) s psoriaticheskim artritom [Association of polymorphic markers of the IL4 (C-590T) and IL10 (C-597A) genes with psoriatic arthritis]. Byulleten` Vostochno-Sibirskogo nauchnogo tsentra SO RAMN – Bulletin of East Siberian Academy of Medical Sciences, 2012, vol. 85, no. 3, part 2, pp. 190-193.
5. Smolnikova M.V., Smirnova S.V. Osobennosti raspredeleniya polimorfizma genov TNFA G-308A i IL2 T-330G u bol`nykh psoriaticheskim artritom. Rossiyskiy immunologicheskiy zhurnal (Russian Journal of Immunology): Materialy Ob'edinennogo immunologicheskogo foruma, 30 iyunya – 5 iyulya 2013.[Features of polymorphism distribution of genes TNFA G-308A and IL2 T-330G in patients with psoriatic arthritis]. Russian Journal of Immunology – Russian Journal of Immunology, 2013, vol. 7 (16), no. 2-3, p. 239
6. Al-Heresh A.M., Proctor J., Jones S.M., Dixey J., Cox B., Welsh K., McHugh N. Tumour necrosis factoralpha polymorphism and the HLA-Cw*0602 allele in psoriatic arthritis. Rheumatology (Oxford), 2002, vol. 41, no. 5, pp. 525-530.
7. Baker B.S., Fry L. The immunology of psoriasis. Br. J. Dermatol., 1992, vol. 126, pp. 1-9.
8. Balding J., Kane D., Livingstone W., Mynett-Johnson L., Bresnihan B., Smith O.,FitzGerald O. Cytokine gene polymorphisms: association with psoriatic arthritis susceptibility and severity. Arthritis Rheum., 2003, vol. 48, no. 5, pp. 1408-1413.
9. Baran W., Szepietowski J.C., Mazur G., Baran E. IL-6 and IL-10 promoter gene polymorphisms in psoriasis vulgaris. Acta Derm Venereol., 2008, vol. 88, no. 2, pp. 113-116.
10. Bowes J., Eyre S., Flynn E., Ho P., Salah S., Warren R.B., Marzo-Ortega H., Coates L., McManus R., Ryan A.W., Kane D., Korendowych E., McHugh N., FitzGerald O., Packham J., Morgan A.W., Griffiths C.E., Bruce I.N., Worthington J., Barton A. Evidence to support IL-13 as a risk locus for psoriatic arthritis but not psoriasis vulgaris. Ann. Rheum. Dis., 2011, vol. 70, no. 6, pp. 1016-1019.
11. Burden A.D., Javed S., Bailey M., Hodgins M., Connor M., Tillman D. Genetics of psoriasis: paternal inheritance and a locus on chromosome 6p. J. Invest. Dermatol., 1998, vol. 110, no. 6, pp. 958-960.
12. Capon F., Di Meglio P., Szaub J., Prescott N.J., Dunster C., Baumber L., Timms K., Gutin A., Abkevic V.,Burden A.D., Lanchbury J., Barker J.N., Trembath R.C., Nestle F.O. Sequence variants in the genes for the interleukin-23 receptor (IL23R) and its ligand (IL12B) confer protection against psoriasis. Hum Genet., 2007, vol. 122, no. 2, pp. 201-206.
13. Cargill M., Schrodi S.J., Chang M., Garcia V.E., Brandon R., Callis K.P., Matsunami N., Ardlie K.G., Civello D., Catanese J.J., Leong D.U., Panko J.M., McAllister L.B., Hansen C.B., Papenfuss J., Prescott S.M., White T.J., Leppert M.F., Krueger G.G., Begovich A.B. A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes. Am. J. Hum. Genet., 2007, vol. 80, no. 2, pp. 273-290.
14. Chang Y.T., Chou C.T., Yu C.W., Lin M.W., Shiao Y.M., Chen C.C., Huang C.H., Lee D.D., Liu H.N., Wang W.J., Tsai S.F. Cytokine gene polymorphisms in Chinese patients with psoriasis. Br. J. Dermatol., 2007, vol. 156, no. 5, pp. 899-905.
15. Di Renzo L., Bianchi A., Saraceno R., Calabrese V., Cornelius C., Iacopino L., Chimenti S., De Lorenzo A. -174G/C IL-6 gene promoter polymorphism predicts therapeutic response to TNF-α blockers. Pharmacogenet Genomics, 2012, vol. 22, no. 2, pp. 134-142.
16. Duffin K.C., Freeny I.C., Schrodi S.J., Wong B., Feng B.J., Soltani-Arabshahi R., Rakkhit T., Goldgar D.E., Krueger G.G. Association between IL13 polymorphisms and psoriatic arthritis is modified by smoking. J. Invest. Dermatol., 2009, vol. 129, no. 12, pp. 2777-2783.
17. Eder L., Chandran V., Pellett F., Pollock R., Shanmugarajah S., Rosen C.F., Rahman P., Gladman D.D. IL13 gene polymorphism is a marker for psoriatic arthritis among psoriasis patients. Ann. Rheum. Dis., 2011, vol. 70, no. 9, pp. 1594-1598.
18. Filer C., Ho P., Smith R.L., Griffiths C., Young H.S., Worthington J., Bruce I.N., Barton A. Investigation of association of the IL12B and IL23R genes with psoriatic arthritis. Arthritis Rheum., 2008, vol. 58, no. 12, pp. 3705-3709.
19. Garcia V.E., Chang M., Brandon R., Li Y., Matsunami N., Callis-Duffin K.P., Civello D., Rowland C.M., Bui N., Catanese J.J., Krueger G.G., Leppert M.F., Begovich A.B., Schrodi S.J. Detailed genetic characterization of the interleukin-23 receptor in psoriasis. Genes Immun., 2008, vol. 9, no. 6, pp. 546-555.
20. Giardina E., H ffmeier U., Ravindran J., Behrens F., Lepre T., McHugh N.J., Korendowych E., Burkhardt H., Novelli G., Reis A. Tumor necrosis factor promoter polymorphism TNF*-857 is a risk allele for psoriatic arthritis independent of the PSORS1 locus. Arthritis Rheum., 2011, vol. 63, no. 12, pp. 3801-3806.
21. Gladman D.D., Anhorn K.A., Schachter R.K., Mervat H. HLA antigens in psoriatic arthritis. J. Rheumatol., 1986, vol. 13, pp. 586-592.
22. Gladman D.D., Cheung C., Ng C.M., Wade J.A. HLA-C locus alleles in patients with psoriatic arthritis (PsA). Hum. Immunol., 1999, vol. 60, pp. 259-261.
23. Gottlieb A.B., Krueger J.G. HLA region genes and immune activation in the pathogenesis of psoriasis [comment]. Arch. Dermatol., 1990, vol. 126, pp. 1083-1086.
24. H ffmeier U., Lascorz J., B hm B., Lohmann J., Wendler J., M ssner R., Reich K., Traupe H., Kurrat W., Burkhardt H., Reis A. Genetic variants of the IL-23R pathway: association with psoriatic arthritis and psoriasis vulgaris, but no specific risk factor for arthritis. J. Invest. Dermatol., 2009, vol. 129, no. 2, pp. 355-358.
25. Jadon D., Tillett W., Wallis D., Cavill C., Bowes J., Waldron N., Dixon A., Sengupta R., Barton A., Korendowych E., McHugh N.J. Exploring ankylosing spondylitis-associated ERAP1, IL23R and IL12B gene polymorphisms in subphenotypes of psoriatic arthritis. Rheumatology (Oxford), 2013, vol. 52, no. 2, pp. 261-266.
26. Kane D.J., Gracie J.A., Karanam S. IL-12, IL-15 and IL-18 expression in psoriatic arthritis synovium. Arthritis Rheum., 2003, vol. 48, pp. S55.
27. Kim T.G., Pyo C.W., Hur S.S., Kim Y.K., Hwang H.Y., Youn J.I., Kim T.Y. Polymorphisms of tumor necrosis factor (TNF) alpha and beta genes in Korean patients with psoriasis. Arch. Dermatol Res., 2003, vol. 295, no. 1, pp. 8-13.
28. Kim Y.K., Pyo C.W., Choi H.B., Kim S.Y., Kim T.Y., Kim T.G. Associations of IL-2 and IL-4 gene polymorphisms with psoriasis in the Korean population. J. Dermatol Sci., 2007, vol. 48, no. 2, pp. 133-139.
29. Kingo K., K ks S., Silm H., Vasar E. IL-10 promoter polymorphisms influence disease severity and course in psoriasis. Genes Immun., 2003, vol. 4, no. 6, pp. 455-457.
30. Kingo K., M ssner R., R tsep R., Raud K., Kr ger U., Silm H., Vasar E., Reich K., K ks S. Association analysis of IL20RA and IL20RB genes in psoriasis. Genes Immun., 2008, vol. 9, no. 5, pp. 445-451.
31. Lascorz J., H ffmeier U., Schulze-Koops H., Skapenko A., Reis A., Lohmann J., Wendler J., Traupe H., K ster W., Burkhardt H. Lack of genetic association of the interleukin-4 receptor single-nucleotide polymorphisms I50V and Q551R with erosive disease in psoriatic arthritis. Arthritis Rheum., 2006, vol. 54, no. 12, pp. 4023-4024.
32. Lee Y.H., Choi S.J., Ji J.D., Song G.G. Associations between interleukin-10 polymorphisms and susceptibility to psoriasis: a meta-analysis. Inflamm. Res., 2012, vol. 61, no. 7, pp. 657-663.
33. Li C., Wang G., Gao Y., Liu L., Gao T. TNFα gene promoter -238G>A and -308G>A polymorphisms alter risk of psoriasis vulgaris: a meta-analysis. J. Invest. Dermatol., 2007, vol. 127, no. 8, pp. 1886-1892.
34. 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, vol. 28, no. 4 (3), p. e1000041.
35. Liu Y., Krueger J.G., Bowcock A.M. Psoriasis: genetic associations and immune system changes. Genes and Immunity, 2007, no. 8, pp. 1-12.
36. Magalh es R.F., Biral A.C., Pancoto J.A., Donadi E.A., Mendes C.T. Jr., Magna L.A., Kraemer M.H. Human leukocyte antigen (HLA) and single nucleotide polymorphisms (SNPs) tumor necrosis factor TNFα-238 and -308 as genetic markers of susceptibility to psoriasis and severity of the disease in a long-term follow-up Brazilian study. Int. J. Dermatol., 2010, vol. 49, no. 10, pp. 1133-1140.
37. Mease P. TNFα therapy in psoriatic arthritis and psoriasis. Ann. Rheum. Dis., 2004, vol. 63, no. 7, pp. 755-758.
38. Murray C., Mann D.L., Gerber L.N., Barth W., Perlmann S., Decker J.L., Nigra T.P. Histocompatibility alloantigens in psoriasis and psoriatic arthritis. Evidence for the influence of multiple genes in the major histocompatibility complex. J. Clin. Invest., 1980, vol. 66, pp. 670-675.
39. Nair R.P., Duffin K.C., Helms C., Ding J., Stuart P.E., Goldgar D., Gudjonsson J.E., Li Y., Tejasvi T., Feng B.J., Ruether A., Schreiber S., Weichenthal M., Gladman D., Rahman P., Schrodi S.J., Prahalad S., Guthery S.L., Fischer J., Liao W., Kwok P.Y., Menter A., Lathrop G.M., Wise C.A., Begovich A.B., Voorhees J.J., Elder J.T., Krueger G.G., Bowcock A.M., Abecasis G.R; Collaborative Association Study of Psoriasis. Genomewide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways. Nat. Genet., 2009, vol. 41, no. 2, pp. 199-204.
40. Nair R.P., Guo S.W., Jenisch S., Henseler T., Lange E.M., Terhune M., Westphal E., Christophers E., Voorhees J.J., Elder J.T. Scanning chromosome 17 for psoriasis susceptibility: lack of evidence for a distal 17q locus. Hum. Hered., 1995, vol. 45, no. 4, pp. 219-230.
41. Nair R.P., Ruether A., Stuart P.E., Jenisch S., Tejasvi T., Hiremagalore R., Schreiber S., Kabelitz D., Lim H.W., Voorhees J.J., Christophers E., Elder J.T., Weichenthal M. Polymorphisms of the IL12B and IL23R genes are associated with psoriasis. J. Invest. Dermatol., 2008, vol. 128, no. 7, pp. 1653-1661.
42. Nedoszytko B., Szczerkowska-Dobosz A., Zab otna M., Gle J., Reba a K., Roszkiewicz J. Associations of promoter region polymorphisms in the tumour necrosis factor-alpha gene and early-onset psoriasis vulgaris in a northern Polish population. Br. J. Dermatol., 2007, vol. 157, no. 1, pp. 165-167.
43. Nishibu A., Oyama N., Nakamura K., Kaneko F. Lack of association of TNF-238A and -308A in Japanese patients with psoriasis vulgaris, psoriatic arthritis and generalized pustular psoriasis. J. Dermatol. Sci., 2002, vol. 29, no. 3, pp. 181-184.
44. Nograles K.E., Brasington R.D., Bowcock A.M. New insights into the pathogenesis and genetics of psoriatic arthritis. Nat. Clin. Pract. Rheumatol., 2009, vol. 5, no. 2, pp. 83-91.
45. O’Rielly D.D., Rahman P. Where do we stand with the genetics of psoriatic arthritis? Curr Rheumatol Rep., 2010, vol. 12, no. 4, pp. 300-308.
46. Rahman P., Elder J.T. Genetic epidemiology of psoriasis and psoriatic arthritis. Ann Rheum Dis., 2005, vol. 64, suppl 2, pp. 37-39, disc. pp. 40-41.
47. Rahman P., Inman R.D., Maksymowych W.P., Reeve J.P., Peddle L., Gladman D.D. Association of interleukin 23 receptor variants with psoriatic arthritis. J. Rheumatol., 2009, vol. 36, no. 1, pp. 137-140.
48. Rahman P., Siannis F., Butt C., Farewell V., Peddle L., Pellett F., Gladman D. TNFα polymorphisms and risk of psoriatic arthritis. Ann. Rheum. Dis., 2006, vol. 65, no. 7, pp. 919-923.
49. Rahman P., Snelgrove T., Peddle L., Siannis F., Farewell V., Schentag C., Gladman D. A variant of the IL4 I50V single-nucleotide polymorphism is associated with erosive joint disease in psoriatic arthritis. Arthritis Rheum., 2008, vol. 58, no. 7, pp. 2207-2208.
50. Rahman P., Sun S., Peddle L., Snelgrove T., Melay W., Greenwood C., Gladman D. Association between the interleukin-1 family gene cluster and psoriatic arthritis. Arthritis Rheum., 2006, vol. 54, no. 7, pp. 2321-2325.
51. Ravindran J.S., Owen P., Lagan A., Lewis J., Korendowych E., Welsh K., McHugh N. Interleukin 1alpha, interleukin 1beta and interleukin 1 receptor gene polymorphisms in psoriatic arthritis. Rheumatology (Oxford), 2004, vol. 43, no. 1, pp. 22-26.
52. Reich K., H ffmeier U., K nig I.R., Lascorz J., Lohmann J., Wendler J., Traupe H., M ssner R., Reis A., Burkhardt H. TNF polymorphisms in psoriasis: association of psoriatic arthritis with the promoter polymorphism TNF*-857 independent of the PSORS1 risk allele. Arthritis Rheum., 2007, vol. 56, no. 6, pp. 2056-2064.
53. Reich K., M ssner R., K nig I.R., Westphal G., Ziegler A., Neumann C. Promoter polymorphisms of the genes encoding tumor necrosis factor-alpha and interleukin-1beta are associated with different subtypes of psoriasis characterized by early and late disease onset. J. Invest Dermatol., 2002, vol. 118, no. 1, pp. 155-163.
54. Seitz M., Wirthm ller U., M ller B., Villiger P.M. The -308 tumour necrosis factor-alpha gene polymorphism predicts therapeutic response to TNFalpha-blockers in rheumatoid arthritis and spondyloarthritis patients. Rheumatology (Oxford), 2007, vol. 46, no. 1, pp. 93-96.
55. Settin A.A., Hassan H.A., El-Baz R.A., Hassan T.A. Association of cytokine gene polymorphisms with psoriasis in cases from the nile delta of egypt. Indian J. Dermatol., 2011, vol. 56, no. 3, pp. 272-277.
56. Smith R.L., Eyre S., Warren R.B., Young H.S., Griffiths C.E., Worthington J. No association between polymorphisms in the interleukin-15 gene and early-onset psoriasis in a UK cohort suggests heterogeneity for this susceptibility locus identified in Chinese psoriasis patients. J. Invest Dermatol., 2008, vol. 128, no. 12, pp. 2904-2905.
57. Smolnikova M.V., Smirnova S.V., Freidin M.B., Tyutina O.S. Immunological parameters and gene polymorphisms (C-590T IL4, C-597A IL10) in severe bronchial asthma in children from the Krasnoyarsk region, West Siberia. Int. J. of Circumpolar Health, 2013, vol. 72, suppl.1, рр. 554-560.
58. Tsoi L.C., Spain S.L., Knight J., Ellinghaus E., Stuart P.E., Capon F., Ding J., Li Y., Tejasvi T., Gudjonsson J.E., Kang H.M., Allen M.H., McManus R., Novelli G., Samuelsson L., Schalkwijk J., St hle M., Burden A.D., Smith C.H., Cork M.J., Estivill X., Bowcock A.M., Krueger G.G., Weger W., Worthington J., Tazi-Ahnini R., Nestle F.O., Hayday A., Hoffmann P., Winkelmann J., Wijmenga C., Langford C., Edkins S., Andrews R., Blackburn H., Strange A., Band G., Pearson R.D., Vukcevic D., Spencer C.C., Deloukas P., Mrowietz U., Schreiber S., Weidinger S., Koks S., Kingo K., Esko T., Metspalu A., Lim H.W., Voorhees J.J., Weichenthal M., Wichmann H.E., Chandran V., Rosen C.F., Rahman P., Gladman D.D., Griffiths C.E., Reis A., Kere J.; Collaborative Association Study of Psoriasis (CASP); Genetic Analysis of Psoriasis Consortium; Psoriasis Association Genetics Extension; Wellcome Trust Case Control Consortium 2, Nair R.P., Franke A., Barker J.N., Abecasis G.R., Elder J.T., Trembath R.C. Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity. Nat. Genet., 2012, vol. 44, no. 12, pp. 1341-1348.
59. Tsunemi Y., Nishibu A., Saeki H., Oyama N., Nakamura K., Kishimoto M., Mitsui H., Tada Y., Torii H., Komine M., Asahina A., Kaneko F., Tamaki K. Lack of association between the promoter polymorphisms at positions -308 and -238 of the tumor necrosis factor alpha gene and psoriasis vulgaris in Japanese patients. Dermatology, 2003, vol. 207, no. 4, pp. 371-374.
60. Valdimarsson H. The genetic basis of psoriasis. Clin Dermatol., 2007. Vol. 25, no. 6, pp. 563-567.
61. Warren R.B., Smith R.L., Flynn E., Bowes J. UKRAG Consortium, Eyre S., Worthington J., Barton A., Griffiths C.E. A systematic investigation of confirmed autoimmune loci in early-onset psoriasis reveals an association with IL2/IL21. Br. J. Dermatol., 2011, vol. 164, no. 3, pp. 660-664.
62. Weidinger S., Willis-Owen S.A., Kamatani Y., Baurecht H., Morar N., Liang L., Edser P., Street T., Rodriguez E., O’regan G.M., Beattie P., F lster-Holst R., Franke A., Novak N., Fahy C.M., Winge M.C., Kabesch M., Illig T., Heath S., S derh ll C., Mel n E., Pershagen G., Kere J., Bradley M., Lieden A., Nordenskjold M., Harper J.I., Irwin McLean W.H., Brown S.J., Cookson W.O., Mark Lathrop G., Irvine A.D., Moffatt M.F. A genome-wide association study of atopic dermatitis identifies loci with overlapping effects on asthma and psoriasis. Hum Mol Genet., 2013. [Epub ahead of print]
63. Yang Q., Liu H., Qu L., Fu X., Yu Y., Yu G., Tian H., Yu Y., Sun D., Peng J., Bao F., Yuan C., Lu N., Li J., Zhang Y., Zhang F. Investigation of 20 non-HLA (human leucocyte antigen) psoriasis susceptibility loci in Chinese patients with psoriatic arthritis and psoriasis vulgaris. Br. J. Dermatol., 2013, vol. 168, no. 5, pp. 1060-1065.
64. Zhang X.J., Yan K.L., Wang Z.M., Yang S., Zhang G.L., Fan X., Xiao F.L., Gao M., Cui Y., Wang P.G., Sun L.D., Zhang K.Y., Wang B., Wang D.Z., Xu S.J., Huang W., Liu J.J. Polymorphisms in interleukin-15 gene on chromosome 4q31.2 are associated with psoriasis vulgaris in Chinese population. J. Invest. Dermatol., 2007, vol. 127, no. 11, pp. 2544-2551.
65. Zhu K.J., Zhu C.Y., Shi G., Fan Y.M. Meta-analysis of IL-12B polymorphisms (rs3212227, rs6887695) with psoriasis and psoriatic arthritis. Rheumatol. Int., 2013, vol. 33, no. 7, pp. 1785-1790.
Для цитирования:
Смольникова М.В., Смирнова С.В. ГЕНЕТИЧЕСКИЕ ФАКТОРЫ В ИММУНОПАТОГЕНЕЗЕ ПСОРИАЗА И ПСОРИАТИЧЕСКОГО АРТРИТА. Медицинская иммунология. 2014;16(3):211-220. https://doi.org/10.15789/1563-0625-2014-3-211-220
For citation:
Smolnikova M.V., Smirnova S.V. GENETIC FACTORS IN IMMUNOPATHOGENESIS OF PSORIASIS AND PSORIATIC ARTHRITIS. Medical Immunology (Russia). 2014;16(3):211-220. (In Russ.) https://doi.org/10.15789/1563-0625-2014-3-211-220
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