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Effective Therapeutical Modulation of the Inflammation in Patients with Psoriasis Using Guselkumab Targeting the Specific Subunit p19 IL-23 of the Regulatory Axis of IL-23/Th17


Authors: J. Krejsek
Authors‘ workplace: Ústav klinické imunologie a alergologie, LF UK a FN Hradec Králové, přednosta prof. RNDr. Jan Krejsek, CSc.
Published in: Čes-slov Derm, 93, 2018, No. 6, p. 244-249
Category:

Overview

The special role in the pathogenesis of psoriasis is given to keratinocytes which are releasing damage associated molecular patterns (DAMP) as a consequence of the exposure to the various noxious stimuli. The identification of DAMP by PRR receptor is followed by the both local and systemic release of proinflammatory cytokines. Some DAMP pattern, so called alarmins, are processed in dendritic cells and are presented as antigenic fragments in optimal cytokine and costimulatory microenvironment to T cells. The abnormal functional polarisation of proliferating T cells in to Th17, Th1, and Th22 subsets is the consequence of this presentation. The critical role into the polarisation to the Th1 and Th17 subsets is given to IL-12 and IL-23 cytokines which share in their unique dimeric structures the common subunit p40. IL-23 is irreplaceable for the whole activity of Th17 subset. This concept is evidenced by the excellent results of several clinical studies in which the neutralisation of p19 subunit specific for IL-23 by guselkumab is substantially alleviating clinical activity of psoriasis. The clinical efficacy and excellent safety profil of guselkumab is superior to other biologicals used in the treatment of psoriasis.

Keywords:

IL – p – guselkumab – biological therapy


Sources

1. Albanesi, C., Madonna, S., Gisondi, P., et al. The interplay between keratinocytes and immune cells in the pathogenesis of psoriasis. Front Immunol, 2018, 9 (1549), p. 1-7.

2. Blauvelt, A., Papp, KA., Griffiths, ChEM., et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate to severe psoriasis. Results from the phase III, double-blinded, placebo- and active comparator-controlled VOYAGE 1 trial. J Am Acad Dermatol, 2016, http://dx.doi.org/10.1016/j.jaad.2016.11.041.

3. Bridgewood, Ch., Fearnley, GW., Berekmeri, A., et al. IL-36γ is a strong inducer of IL-23 in psoriatic cells and activates angiogenesis. Front Immunol, 2018, 9 (200), p. 1-12.

4. Coates, LC., FitzGerald, O., Helliwell, PS., et al. Psoriasis, psoriatic arthritis, and rheumatoid arthritis: is all inflammation the same? Semin Arthrit Rheumatism, 2016, 46, p. 291-304.

5. Diani, M., Altomare, G., Reali, E. T cell responses in psoriasis and psoriatic arthritis. Autoimmun Rev, 2015, 14 (4), p. 286-92.

6. Fotiadou, Ch., Lazaridou, E., Sotiriou, E., et al. Targeting IL-23 in psoriasis: current perspectives. Psoriasis: Targets Ther, 2018, 8, p. 1-5.

7. Hawkes, JE., Chan, TC., Krueger, JG. Psoriasis pathogenesis and the development of novel targeted immune therapies. J Allergy Clin Immunol, 2017, 140 (3), p. 645-653.

8. Kim, J., Krueger, JG. The immunopathogenesis of psoriasis. Dermatol Clin, 2015 33 (1), p. 13-23.

9. Krejsek, J., Andrýs, C., Krčmová, I. Imunologie člověka. 1. vyd. Hradec Králové: Garamon, 2016. 496 s. ISBN: 978-80-86472-74-4. http://www.imunologie-cloveka-krejsek.cz

10. Kuwabara, T., Ishikawa, F., Kondo, M., et al. The role of IL-17 and related cytokines in inflammatory autoimmune diseases. Med Inflam, 2017, http://dx.doi.org/ 10.1155/2017/3908061.

11. Lanfranca, MP., Lin, Y., Fang, J., et al. Biological and pathological activities of interleukin-22. J Mol Med, 2016, 94, p. 523-534.

12. Machado, Á., Torres, T. Guselkumab for the treatment of psoriasis. BioDrugs, 2018, https://doi.org/10.1007/s40259-018-0265-6.

13. Mylle, S., Grine, L., Speeckaert, R., et al. Targeting the IL-23/IL-17 pathway in psoriasis: the search for the good, the bad and the ugly. Am J Clin Dermatol, 2018, doi: 10.1007/s40257-018-0366-5.

14. Puig, L. The role of IL-23 in the treatment of psoriasis. Expert Rev Clin Immunol, 2017, 13 (6), p. 525-534.

15. Rapalli, VK., Singhvi, G., Dubey, SK., et al. Emerging landscape in psoriasis management: From topical application to targeting biomolecules. Biomed Pharmacother, 2018, 106, p. 707-713.

16. Saeterdal, I., Mork, NJ., Dalaker, M., et al. TNF–α inhibitors and efalizumab for the treatment of skin diseases. Oslo, Norway: Knowledge Centre for the Health Services at The Norwegian Institute of Public Health (NIPH); 2007 May. Report from Norwegian Knowledge Centre for the Health Services (NOKC) No. 15-2007.

17. Salem, I., Ramser, A., Isham, N., et al. The gut microbiome as a major regulator of the gut-skin axis. Frontiers Microbiol, 2018, 9 (1459), p. 1-14.

18. Sator, P. Safety and tolerability of adalimumab for the treatment of psoriasis: a review summarizing 15 years of real-life experience. Ther Adv Chronic Dis, 2018, 9 (8), 147-158.

19. Schön, MP., Erpenbeck, L. The interleukin-23/Interleukin-17 axis links adaptive and innate immunity in psoriasis. Front Immunol, 2018, 9 (1323), p. 1-11.

20. Sil, P., Wong, SW., Martinez, J. More than skin deep: autophagy is vital for skin barrier function. Front Immunol, 2018, 9 (1376), p. 1-14.

21. Sud, V., Abboud, A., Tohme, S., et al. IL-17A – A regulator in acute inflammation: Insights from in vitro, in vivo and in silico studies. Cytokine, 2018, S1043-4666 (18), p. 30116-9.

22. Tai, Y., Wang, Q., Korner, H., et al. Molecular mechanisms of T cells activation by dendritic cells in autoimmune diseases. Front Pharmacol, 2018, 9 (642), p. 1-10.

23. Taylor, PR., Roy, S., Leal, SM., et al. Activation of neutrophils by autocrine IL-17A-IL-17RC interactions during fungal infection is regulated by IL-6, IL-23, RORγt and dectin-2. Nature Immunol, 2014, 15 (2), p. 143-151.

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Dermatology & STDs Paediatric dermatology & STDs
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