Abstract
Psoriasis is an inflammatory skin disease characterized by keratinocyte hyperproliferation with effective environmental and genetic factors. Recent studies showing that the IL-23/IL-17 axis plays a central role in the pathogenesis of the disease. Experimental and clinical studies suggest that IL-17A, an important regulatory effector cytokine in this pathway and triggers changes mainly in affected tissues. Based on the central role of IL-17A in the pathogenesis of psoriasis, we thought that variations in this gene could affect the susceptibility and severity of this disease. Therefore, in this study, we aimed to analyze whether IL-17A rs10484879 variant has an effect on psoriasis pathogenesis in Turkish population. In this case–control study, the study group consisting of 564 patient (188 psoriasis patients (66 males/122 females)/376 controls (132 males/244 females) and they were genotyped in terms of IL-17A (rs10484879) polymorphism with TaqMan 5 'Allelic Discrimination Test. IL-17A serum levels were measured with the Enzyme-linked immunosorbent assay (ELISA). The genotype distributions of the IL-17A rs10484879 polymorphism between the patient and control groups were statistically different in the TT genotype and it was observed more commonly in the patient group compared to the controls (p < 0.001). Similarly, the T allele was observed with a higher prevalence in the patient group compared to the controls (p = 0.007). IL-17A serum levels were associated with increased serum concentration, respectively, TT > GT > GG in all study groups (p < 0.05). We would like to report that IL-17A rs10484879 TT genotype and T allele are associated with increased risk of psoriasis in the Turkish population.
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References
Boehncke WH, Schön MP (2015) Psoriasis. Lancet 5:983–994
Nestle FO, Kaplan DH, Barker J (2009) Psoriasis. N Engl J Med 361:496–509
Andrew B, Andrea C (2018) The immunologic role of IL-17 in psoriasis and psoriatic arthritis pathogenesis. Clin Rev Allergy Immunol 55:379–390
Lowes MA, Suárez-Fariñas M, Krueger JG (2014) Immunology of psoriasis. Annu Rev Immunol 32:227–255
Chiricozzi A, Guttman-Yassky E, Suárez-Fariñas M et al (2011) Integrative responses to IL-17 and TNF-α in human keratinocytes account for key inflammatory pathogenic circuits in psoriasis. J Invest Dermatol 131:677–687
Martin DA, Towne JE, Kricorian G et al (2013) The emerging role of IL-17 in the pathogenesis of psoriasis: preclinical and clinical findings. J Invest Dermatol 133:17–26
Chiricozzi A, Suárez-Fariñas M, Fuentes-Duculan J et al (2016) Increased expression of interleukin-17 pathway genes in nonlesional skin of moderate-to-severe psoriasis vulgaris. Br J Dermatol 174:136–145
Belasco J, Louie JS, Gulati N et al (2015) Comparative genomic profiling of synovium versus skin lesions in psoriatic arthritis. Arthritis Rheumatol 67:934–944
Caproni M, Antiga E, Melani L et al (2009) Serum levels of IL-17 and IL-22 are reduced by etanercept, but not by acitretin, in patients with psoriasis: a randomized-controlled trial. J Clin Immunol 29:210–214
Ortega C, Fernandez AS, Carrillo JM et al (2009) IL-17-producing CD8+ T lymphocytes from psoriasis skin plaques are cytotoxic effector cells that secrete Th17-related cytokines. J Leukocyte Biol 86:435–443
Chiricozzi A, Nograles KE, Johnson-Huang LM et al (2014) L-17 induces an expanded range of downstream genes in reconstituted human epidermis model. PLoS ONE. https://doi.org/10.1371/journal.pone.0090284
Nograles KE, Zaba LC, Guttman-Yassky E et al (2008) Th17 cytokines interleukin (IL)-17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways. Br J Dermatol 159:1092–1102
Harper EG, Guo C, Rizzo H et al (2009) Th17 cytokines stimulate CCL20 expression in keratinocytes in vitro and in vivo: implications for psoriasis pathogenesis. J Invest Dermatol 129:2175–2183
Lande R, Botti E, Jandus C et al (2014) The antimicrobial peptide LL37 is a T-cell autoantigen in psoriasis. Nat Commun 5:5621
Krueger JG (2015) An autoimmune “attack” on melanocytes triggers psoriasis and cellular hyperplasia. J Exp Med 212:2186
Arakawa A, Siewert K, Stöhr J et al (2015) Melanocyte antigen triggers autoimmunity in human psoriasis. J Exp Med 212:2203–2212
Verstrepen L, Carpentier I, Verhelst K et al (2009) A20 binding inhibitors of NF-kappa B and apoptosis signaling. Biochem Pharmacol 15:105–114
Gaffen SL (2009) Structure and signalling in the IL-17 receptor family. Nat Rev Immunol 9:556–567
Langley RG, Elewski BE, Lebwohl M et al (2014) Secukinumab in plaque psoriasis—results of two phase 3 trials. N Engl J Med 371:326–338
Hueber W, Patel DD, Dryja T et al (2010) Effects of AIN457, a fully human antibody to interleukin-17A, on psoriasis, rheumatoid arthritis, and uveitis. Sci Transl Med. 6:52ra72
Karen L, Smith MP, Thibodeaux Q et al (2019) Anti IL-17 in psoriasis. Expert Rev Clin Immunol 15:1185–1194
Bissonnette R, Luger T, Thaçi D et al (2018) Secukinumab demonstrates high sustained efficacy and a favourable safety profile in patients with moderate-to-severe psoriasis through 5 years of treatment (SCULPTURE Extension Study). J Eur Acad Dermatol Venereol 32:1507–1514
Nast A, Amelunxen L, Augustin M et al (2018) Guideline for the treatment of psoriasis vulgaris, update—short version part 1—systemic treatment. J Dtsch Dermatol Ges 16:645–669
World Medical Association (2013) World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA 310:2191–2194
https://www.psychologie.hhu.de/arbeitsgruppen/allgemeine-psychologie-und-arbeitspsychologie/gpower
Elder JT, Bruce AT, Gudjonsson JE et al (2010) Molecular dissection of psoriasis: integrating genetics and biology. J Invest Dermatol 130:1213–1226
Krueger JG, Fretzin S, Suarez-Farinas M et al (2012) IL-17A is essential for cell activation and inflammatory gene circuits in subjects with psoriasis. J Allergy Clin Immunol 130:145
Chiricozzi A, Romanelli P, Volpe E et al (2018) Scanning the immunopathogenesis of psoriasis. Int J Mol Sci 19:179
Banuelos J, Cao Y, Shin SC, Lu NZ (2017) Immunopathology alters Th17 cell glucocorticoid sensitivity. Allergy 72:331–341
Xu S, Cao X (2010) Interleukin-17 and its expanding biological functions. Cell Mol Immunol 7:164
Diani M, Altomare G, Reali E (2016) T helper cell subsets in clinical manifestations of psoriasis. J Immunol Res. https://doi.org/10.1155/2016/7692024
Giunta A, Ventura A, Chimenti MS et al (2017) Spotlight on ixekizumab for the treatment of moderate-to-severe plaque psoriasis: design, development, and use in therapy. Drug Des Dev Ther 11:1643–1651
Białecka M, Ostasz R, Kurzawski M et al (2016) IL17A and IL17F gene polymorphism association with psoriasis risk and response to treatment in a Polish population. Dermatology 232:592–596
Kim SY, Hur MS, Choi BG et al (2017) A preliminary study of new single polymorphisms in the T helper type 17 pathway for psoriasis in the Korean population. Clin Exp Immunol 187:251–258
Batalla A, Coto E, González-Lara L et al (2015) Association between single nucleotide polymorphisms IL17RA rs4819554 and IL17E rs79877597 and Psoriasis in a Spanish cohort. J Dermatol Sci 80:111–155
Rocío PP, Guillermo SL, Teresa C et al (2015) The polymorphism rs763780 in the IL-17F gene is associated with response to biological drugs in patients with psoriasis. Pharmacogenomics 16:1723–1731
Rajinder K, Arun KR, Sunil K et al (2018) Association of genetic polymorphism of interleukin-17A and interleukin-17F with susceptibility of psoriasis. Indian J Med Res 148:422–426
Silje MS, Lene FS, Marianne E et al (2018) Serum cytokine measurements and biological therapy of psoriasis—prospects for personalized treatment? Scand J Immunol. https://doi.org/10.1111/sji.12725
Blauvelt A, Ferris LK, Yamauchi PS et al (2017) Extension of ustekinumab maintenance dosing interval in moderate-to-severe psoriasis: results of a phase IIIb, randomized, double-blinded, active-controlled, multicentre study (PSTELLAR). Br J Dermatol 177:1552–1561
Teng MWL, Bowman EP, Elwe JJM et al (2015) IL-12 and IL-23 cytokines: from discovery to targeted therapies for immune-mediated inflammatory diseases. Nat Med 21:719–729
Branigan PJ, Liu X, Chen Y et al (2017) Guselkumab attenuates disease- and mechanism-related biomarkers in patients with moderate-to-severe plaque psoriasis. J Invest Dermatol 137:51
Acknowledgements
The present study was supported by a grant from the Scientific Research Projects Coordination Unit of Giresun University (Project No: SAĞ-BAP-A-270220-07).
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Akşan, B., Akadam-Teker, A.B. Genetic variants in IL-17A rs10484879 and serum levels of IL-17A are associated with psoriasis risk. Arch Dermatol Res 314, 937–942 (2022). https://doi.org/10.1007/s00403-021-02308-w
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DOI: https://doi.org/10.1007/s00403-021-02308-w