Effect of PUVA on Janus Kinase/Signal Transducer and Activator of Transcription Pathway in Patients with Vitiligo

Document Type : Original Article

Authors

1 Dermatology and Venereology department, Faculty of Medicine, Beni-Suef University, Egypt

2 Dermatology and Venereology department, Beni-Suef, Egypt

3 Biochemistry department, Faculty of Medicine, Cairo University, Egypt

Abstract

The aim of the current study was to detect effect of PUVA on JAK/STAT pathway and its relationship with the pathogenesis of Vitiligo. It was a Case-Control study conducted from Abril 2019 to December 2019 in the Dermatology outpatient clinic at Beni-Suef Univeristy Hospital and included 30 patients that had Vitiligo disease (7 males and 23 females), their age ranged from 20 to 50 years, the average age was 33.73±8.7. And 30 age and sex matched healthy controls. All participants were subjected to full clinical and laboratory investigations. Skin biopsies had been taken from all studied participants (Vitiligo cases and healthy controls) to study effect of PUVA on JAK/STAT pathway and its relationship with the pathogenesis of Vitiligo. Tissue expression of JAK/STAT was significantly higher in Vitiligo  skin lesions as compared with healthy skin biopsies taken from controls both before and even after exposure to PUVA. Tissue expression of JAK/STAT decreased significantly after exposure to PUVA in Vitiligo skin lesions. Tissue expression of JAK was significantly higher in Vitiligo skin lesions in patients with positive as compared with negative family history. There was a significant linear moderate positive correlation between tissue expression of STAT and patients’ age among studied Vitiligo patients. There was a significant linear moderate negative correlation between tissue expression of STAT and duration of last new lesion among studied Vitiligo patients. There was a significant linear moderate positive correlation between tissue expression of STAT and Vitiligo disease activity (VIDA) score among studied Vitiligo patients. JAK and STAT tissue expression showed a significant linear strong positive correlation among studied population. We suggest that JAK/STAT plays an important role in the pathogenesis of the Vitiligo disease. This could also open a new era for treatment of Vitiligo disease by anti-JAK modalities.

Keywords

Main Subjects


  1. Bergqvist, C., & Ezzedine, K. (2020). Vitiligo: a review. Dermatology, 236(6), 571-592.‏
  2. Wang, Y., Li, S., & Li, C. (2019). Perspectives of new advances in the pathogenesis of vitiligo: from oxidative stress to autoimmunity. Medical science monitor: international medical journal of experimental and clinical research, 25, 1017.‏
  3. Shi, Q., Zhang, W., Guo, S., Jian, Z., Li, S., Li, K., ... & Li, C. (2016). Oxidative stress-induced overexpression of miR-25: the mechanism underlying the degeneration of melanocytes in vitiligo. Cell Death & Differentiation, 23(3), 496-508.‏
  4. Li, M., Fan, Y., Wang, Y., Xu, J., & Xu, H. (2020). ZMIZ1 promotes the proliferation and migration of melanocytes in vitiligo. Experimental and Therapeutic Medicine, 20(2), 1371-1378.‏
  5. Favoino, E., Prete, M., Catacchio, G., Ruscitti, P., Navarini, L., Giacomelli, R., & Perosa, F. (2021). Working and safety profiles of JAK/STAT signaling inhibitors. Are these small molecules also smart?. Autoimmunity Reviews, 102750.‏
  6. Roskoski Jr, R. (2016). Janus kinase (JAK) inhibitors in the treatment of inflammatory and neoplastic diseases. Pharmacological research, 111, 784-803.‏
  7. Morris, R., Kershaw, N. J., & Babon, J. J. (2018). The molecular details of cytokine signaling via the JAK/STAT pathway. Protein Science, 27(12), 1984-2009.‏
  8. Bergqvist, C., & Ezzedine, K. (2021). Vitiligo: A focus on pathogenesis and its therapeutic implications. The Journal of Dermatology, 48(3), 252-270.‏
  9. Nada, H. R., El Sharkawy, D. A., Elmasry, M. F., Rashed, L. A., & Mamdouh, S. (2018). Expression of Janus Kinase 1 in vitiligo & psoriasis before and after narrow band UVB: A case–control study. Archives of dermatological research, 310(1), 39-46.‏
  10. Knobler, R. M., Hönigsmann, H., & Edelson, R. L. (2018). Psoralen phototherapies. In Psoralen DNA photobiology (pp. 117-133). CRC Press.‏
  11. Mahira, S., Kommineni, N., Doppalapudi, S., & Khan, W. (2019). Edge activated ultradeformable liposomes of psoralen and its derivatives: Development and comparative evaluation for vitiligo therapy. Journal of Drug Delivery Science and Technology, 52, 83-95.‏
  12. Xin, P., Xu, X., Deng, C., Liu, S., Wang, Y., Zhou, X., ... & Sun, S. (2020). The role of JAK/STAT signaling pathway and its inhibitors in diseases. International Immunopharmacology, 80, 106210.‏
  13. Relke, N., & Gooderham, M. (2019). The use of Janus kinase inhibitors in vitiligo: a review of the literature. Journal of cutaneous medicine and surgery, 23(3), 298-306.‏‏
  14. Van Den Boorn, J. G., Konijnenberg, D., Dellemijn, T. A., Van Der Veen, J. W., Bos, J. D., Melief, C. J., ... & Luiten, R. M. (2009). Autoimmune destruction of skin melanocytes by perilesional T cells from vitiligo patients. Journal of Investigative Dermatology, 129(9), 2220-2232.‏
  15. Seif El Nasr, H., Shaker, O. G., Fawzi, M. M. T., & El‐Hanafi, G. (2013). Basic fibroblast growth factor and tumour necrosis factor alpha in vitiligo and other hypopigmented disorders: suggestive possible therapeutic targets.Journal of the European Academy of Dermatology and Venereology, 27(1), 103-108.‏
  16. Klarquist, J., Denman, C. J., Hernandez, C., Wainwright, D. J., Strickland, F. M., Overbeck, A., ... & Le Poole, I. C. (2010). Reduced skin homing by functional Treg in vitiligo. Pigment cell & melanoma research, 23(2), 276-286.‏
  17. Kalbasi, A., Tariveranmoshabad, M., Hakimi, K., Kremer, S., Campbell, K. M., Funes, J. M., ... & Torrejon, D. (2020). Uncoupling interferon signaling and antigen presentation to overcome immunotherapy resistance due to JAK1 loss in melanoma. Science Translational Medicine, 12(565).‏
  18. Craiglow, B. G., & King, B. A. (2015). Tofacitinib citrate for the treatment of vitiligo: a pathogenesis-directed therapy. JAMA dermatology, 151(10), 1110-1112.‏
  19. Samaka, R. M., Basha, M. A., & Menesy, D. (2019). Role of Janus kinase 1 and signal transducer and activator of transcription 3 in vitiligo. Clinical, cosmetic and investigational dermatology, 12, 469.‏
  20. Harris, J. E., Rashighi, M., Nguyen, N., Jabbari, A., Ulerio, G., Clynes, R., ... & Mackay-Wiggan, J. (2016). Rapid skin repigmentation on oral ruxolitinib in a patient with coexistent vitiligo and alopecia areata (AA). Journal of the American Academy of Dermatology, 74(2), 370-371.‏
  21. Landry, D. A., Sormany, F., Haché, J., Roumaud, P., & Martin, L. J. (2017). Steroidogenic genes expressions are repressed by high levels of leptin and the JAK/STAT signaling pathway in MA-10 Leydig cells. Molecular and cellular biochemistry, 433(1-2), 79-95.‏
  22. Frank, K., Hamade, H., Casabona, G., Gotkin, R. H., Kaye, K. O., Tiryaki, T., ... & Cotofana, S. (2019). Influences of age, gender, and body mass index on the thickness of the abdominal fatty layers and its relevance for abdominal liposuction and abdominoplasty. Aesthetic surgery journal, 39(10), 1085-1093.‏