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Archives of Dermatological Research

, Volume 310, Issue 1, pp 39–46 | Cite as

Expression of Janus Kinase 1 in vitiligo & psoriasis before and after narrow band UVB: a case–control study

  • Hanan Rabea Nada
  • Dina Ahmed El Sharkawy
  • Maha Fathy ElmasryEmail author
  • Laila Ahmed Rashed
  • Sally Mamdouh
Original Paper
  • 408 Downloads

Abstract

Janus kinases (JAKs) are non-receptor protein tyrosine kinases that are expressed in many tissues. Once the JAKs are activated, a cascade of further signaling events is triggered involving phosphorylation of selected receptor chain tyrosines, binding of signal transducer and activator of transcription (STAT) proteins and phosphorylation of these STATs. Due to their ability to selectively modulate immune function, targeted JAK inhibitors are promising candidates for some skin diseases such as psoriasis and atopic dermatitis. The aim of this study was to assess the level of JAK1 in both vitiligo and psoriasis patients before and after treatment with NB-UVB which is considered a gold standard therapy for both diseases. This study was conducted on 10 patients with psoriasis, 10 patients with vitiligo and 10 controls. JAK1 levels before and after treatment with NB-UVB 311 nm (36 sessions) were measured using Western blot assay. The level of JAK1 was significantly higher in vitiligo and psoriasis patients than controls. There was a decline in the level of JAK1 after treatment, which was statistically significant. VASI and PASI scores of patients decreased after treatment with NB-UVB. In psoriatic patients, the JAK1 level positively correlated with the female participants, disease duration and PASI change. It was concluded that JAK1 plays a role in the pathogenesis of both vitiligo and psoriasis based on its upregulated level before treatment and downregulated level after treatment. This raises the possibility of using the JAK1 inhibitors as targeted immunotherapy for vitiligo and psoriasis.

Keywords

JAK Psoriasis Vitiligo NB-UVB JAK inhibitors 

Abbreviations

CCL

C-C motif chemokine ligand

CNTF-R

Ciliary neurotrophic factor-receptor

CXCL

Chemokine (C-X-C motif) ligand

IFN-R

Interferon receptor

IL

Interleukin

JAK

Janus kinase

LIF-R

Leukemia inhibitory factor-receptor

NB-UVB

Narrow band ultraviolet B

NNT-1R/BSF3R

Novel neurotrophin-1/B cell-stimulating factor-3 receptor

OSM-R/ CT-1R

Oncostatin M/Cardiotrophin-1-receptor

PASI

Psoriasis area and severity index

PTK

Protein tyrosine kinase

STAT

Signal transducer and activator of transcription

Th17

T helper17

TNF-α

Tumor necrosis factor-alpha

TYK

Tyrosine kinase

VASI

Vitiligo area and severity index

Notes

Compliance with ethical standards

Conflict of interest

All the authors declare that they have no conflicts of interest.

Funding

The authors did not receive any external funding for this work.

Ethical approval

All procedures performed in the study were in accordance to the ethical standards of the Dermatology Research Ethical Committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

A written informed consent was obtained from each patient for the participation in the study and photography.

References

  1. 1.
    Aaronson DS, Horvath CM (2002) A road map for those who don’t know JAK-STAT. Science 296(5573):1653–1655CrossRefPubMedGoogle Scholar
  2. 2.
    Andrés RM, Hald A, Johansen C, Kragballe K, Iversen L (2013) Studies of Jak/STAT3 expression and signalling in psoriasis identifies STAT3-Ser727 phosphorylation as a modulator of transcriptional activity. Exp Dermatol 22:323–328.  https://doi.org/10.1111/exd.12128 CrossRefPubMedGoogle Scholar
  3. 3.
    Attwa E, Gamil H, Assaf M, Ghonemy S (2012) Over-expression of tumor necrosis factor-α in vitiligo lesions after narrow-band UVB therapy: an immunohistochemical study. Arch Dermatol Res 304:823–830.  https://doi.org/10.1007/s00403-012-1269-6 CrossRefPubMedGoogle Scholar
  4. 4.
    Bach EA, Aguet M, Schreiber RD (1997) The IFN gamma receptor: a paradigm for cytokine receptor signaling. Annu Rev Immunol 15:563–591.  https://doi.org/10.1146/annurev.immunol.15.1.563 CrossRefPubMedGoogle Scholar
  5. 5.
    Basak PY, Adiloglu AK, Koc IG, Tas T, Akkaya VB (2008) Evaluation of activatory and inhibitory natural killer cell receptors in non-segmental vitiligo: a flow cytometric study. J Eur Acad Dermatol Venereol 22:970–976.  https://doi.org/10.1111/j.1468-3083.2008.02681.x CrossRefPubMedGoogle Scholar
  6. 6.
    Bhise SB, Nalawade AD, Wadhawa H (2004) Role of protein tyrosine kinase inhibitors in cancer therapeutics. Indian J Biochem Biophys 41(6):273–280PubMedGoogle Scholar
  7. 7.
    Craiglow BG, King BA(2015)Tofacitinib citrate for the treatment of vitiligo: a pathogenesis-directed therapy. JAMA Dermatol151:1110–1112.  https://doi.org/10.1001/jamadermatol.2015.1520 CrossRefPubMedGoogle Scholar
  8. 8.
    Di Lernia V, Bardazzi F (2016) Profile of tofacitinib citrate and its potential in the treatment of moderate-to-severe chronic plaque psoriasis. Drug Des Devel Ther 10:533–539.  https://doi.org/10.2147/DDDT.S82599 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Elloso MM, Gomez-Angelats M, Fourie AM (2012) Targeting the Th17 pathway in psoriasis. J Leukoc Biol 92:1187–1197.  https://doi.org/10.1189/jlb.0212101 CrossRefPubMedGoogle Scholar
  10. 10.
    Gaffen SL (2009) Structure and signaling in the IL-17 receptor family. Nat Rev Immunol 9(8):556–567.  https://doi.org/10.1038/nri2586 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Galluzzo M, D’Adamio S, Servoli S, Bianchi L, Chimenti S, Talamonti M (2016) Tofacitinib for the treatment of psoriasis. Expert Opin Pharmacother 17(10):1421–1433.  https://doi.org/10.1080/14656566.2016.1195812 CrossRefPubMedGoogle Scholar
  12. 12.
    Ghoreschi K, Laurence A, O’Shea JJ (2009) Janus kinases in immune cell signaling. Immunol Rev 228:273–287.  https://doi.org/10.1111/j.1600-065X.2008.00754.x CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Hamzavi I, Jain H, McLean D, Shapiro J, Zeng H, Lui H (2004) Parametric modeling of narrowband UV-B phototherapy for vitiligo using a novel quantitative tool: the Vitiligo Area Scoring Index. Arch Dermatol 140:677–683.  https://doi.org/10.1001/archderm.140.6.677 CrossRefPubMedGoogle Scholar
  14. 14.
    Harris JE, Rashighi M, Nguyen N, Jabbari A, Ulerio G, Clynes R, Christiano AM, Mackay-Wiggan J (2016) Rapid skin repigmentation on oral ruxolitinib in a patient with coexistent vitiligo and alopecia areata (AA). J Am Acad Dermatol 74(2):370–371.  https://doi.org/10.1016/j.jaad.2015.09.073 CrossRefPubMedGoogle Scholar
  15. 15.
    Hsu L, Armstrong AW (2014) JAK inhibitors: treatment efficacy and safety profile in patients with psoriasis. J Immunol Res 2014: 283617.  https://doi.org/10.1155/2014/283617
  16. 16.
    Ishizaki M, Akimoto T, Muromoto R, Yokoyama M, Ohshiro Y, Sekine Y, Maeda H, Shimoda K, Oritani K, Matsuda T (2011) Involvement of tyrosine kinase-2 in both the IL-12/Th1 and IL-23/Th17 axes in vivo. J Immunol 187:181–189.  https://doi.org/10.4049/jimmunol.1003244 CrossRefPubMedGoogle Scholar
  17. 17.
    Klarquist J, Denman CJ, Hernandez C, Wainwright DA, Strickland FM, Overbeck A, Mehrotra S, Nishimura MI, Le Poole IC (2010) Reduced skin homing by functional Treg in vitiligo. Pigment Cell Melanoma Res 23:276–286.  https://doi.org/10.1111/j.1755-148X.2010.00688.x CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Kofoed K, Skov L, Zachariae C (2015) New drugs and treatment targets in psoriasis. Acta Derm Venereol 95(2):133–139.  https://doi.org/10.2340/00015555-1931 CrossRefPubMedGoogle Scholar
  19. 19.
    Kwatra SG, Dabade TS, Gustafson CJ, Feldman SR (2012) JAK inhibitors in psoriasis: a promising new treatment modality. J Drugs Dermatol 11(8):913–918PubMedGoogle Scholar
  20. 20.
    Lai SY, Johnson FM (2010) Defining the role of the JAK-STAT pathway in head and neck and thoracic malignancies: implications for future therapeutic approaches. Drug Resist Update 13:67–78.  https://doi.org/10.1016/j.drup.2010.04.001 CrossRefGoogle Scholar
  21. 21.
    Landry DA, Sormany F, Haché J, Roumaud P, Martin LJ (2017) Steroidogenic genes expressions are repressed by high levels of leptin and the JAK/STAT signaling pathway in MA-10 Leydig cells. Mol Cell Biochem.  https://doi.org/10.1007/s11010-017-3017-x PubMedGoogle Scholar
  22. 22.
    Ludbrook VJ, Hicks KJ, Hanrott KE, Patel JS, Binks MH, Wyres MR, Watson J, Wilson P, Simeoni M, Schifano LA, Reich K, Griffiths CE (2016) Investigation of selective JAK1 inhibitor GSK2586184 for the treatment of psoriasis in a randomized placebo-controlled phase IIa study. Br J Dermatol 174:985–995.  https://doi.org/10.1111/bjd.14399 CrossRefPubMedGoogle Scholar
  23. 23.
    Marks R, Barton SP, Shuttleworth D, Finlay AY (1989) Assessment of disease progress in psoriasis. Arch Dermatol 125:235–240.  https://doi.org/10.1001/archderm.1989.01670140087017 CrossRefPubMedGoogle Scholar
  24. 24.
    Ortiz-Ibáñez K, Alsina MM, Muñoz-Santos C (2013) Tofacitinib and other kinase inhibitors in the treatment of psoriasis. Actas Dermosifiligor 104:304–310.  https://doi.org/10.1016/j.adengl.2013.03.002 CrossRefGoogle Scholar
  25. 25.
    Papp KA, Menter MA, Raman M, Disch D, Schlichting DE, Gaich C, Macias W, Zhang X, Janes JM (2016) A randomized phase 2b trial of baricitinib, an oral Janus kinase (JAK) 1/JAK2 inhibitor, in patients with moderate-to-severe psoriasis. Br J Dermatol 174(6):1266–1276.  https://doi.org/10.1111/bjd.14403 CrossRefPubMedGoogle Scholar
  26. 26.
    Punwani N, Scherle P, Flores R, Shi J, Liang J, Yeleswaram S, Levy R, Williams W, Gottlieb A (2012) Preliminary clinical activity of a topical JAK1/2 inhibitor in the treatment of psoriasis. J Am Acad Dermatol 67(4):658–64.  https://doi.org/10.1016/j.jaad.2011.12.018 CrossRefGoogle Scholar
  27. 27.
    Rane SG, Reddy EP (2000) Janus kinases: components of multiple signaling pathways. Oncogene 19:5662–5679.  https://doi.org/10.1038/sj.onc.1203925 CrossRefPubMedGoogle Scholar
  28. 28.
    Schindler C, Plumlee C (2008) Inteferons pen the JAK-STAT pathway. Semin Cell Dev Biol 19:311–318.  https://doi.org/10.1016/j.semcdb.2008.08.010 CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Nasr Seif El, Shaker H, Fawzi OG, El-Hanafi MM G (2013) Basic fibroblast growth factor and tumour necrosis factor alpha in vitiligo and other hypopigmented disorders: suggestive possible therapeutic targets. J Eur Acad Dermatol Venereol 27:103–108.  https://doi.org/10.1111/j.1468-3083.2011.04368.x CrossRefGoogle Scholar
  30. 30.
    Sohn SJ, Barrett K, Van Abbema A, Chang C, Kohli PB, Kanda H, Smith J, Lai Y, Zhou A, Zhang B, Yang W et al (2013) A restricted role for TYK2 catalytic activity in human cytokine responses revealed by novel TYK2-selective inhibitors. J Immunol 191:2205–2216.  https://doi.org/10.4049/jimmunol.1202859 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    van den Boorn JG, Konijnenberg D, Dellemijn TA, van der Veen JP, Bos JD, Melief CJ, Vyth-Dreese FA, Luiten RM (2009) Autoimmune destruction of skin melanocytes by perilesional T cells from vitiligo patients. J Invest Dermatol 129:2220–2232.  https://doi.org/10.1038/jid.2009.32 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Dermatology Department, Faculty of MedicineCairo UniversityCairoEgypt
  2. 2.Medical Biochemistry and Molecular Biology Department, Faculty of MedicineCairo UniversityCairoEgypt
  3. 3.CairoEgypt

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