Rekonstytucja układu odpornościowego w wyniku zastosowania preparatu kladrybiny podawanej doustnie Artykuł przeglądowy
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Opublikowane:
mar 31, 2023
Słowa kluczowe:
stwardnienie rozsiane, rekonstytucja, kladrybina, limfocyt
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Abstrakt
Rekonstytucja po zastosowaniu kladrybiny doustnej jest zmianą architektury układu odpornościowego. W wyniku terapii dochodzi do zmniejszenia liczby komórek autoreaktywnych, a zmiana stosunków komórek układu odpornościowego prowadzi do zmiany jego profilu w kierunku bardziej przeciwzapalnym. Analiza danych dotyczących dynamiki stężeń subpopulacji limfocytów wskazuje na dominujący wpływ kladrybiny na limfocyty B, w tym w szczególności na limfocyty B pamięci. Wpływ na limfocyty T jest mniej zaznaczony i charakteryzuje się wolniejszym tempem repopulacji. Kontrolowana proliferacja limfocytów B dzięki względnie zaoszczędzonym limfocytom T może być odpowiedzialna za brak wtórnych autoimmunizacji.
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Bibliografia
1. Giovannoni G, Mathews J. Cladribine Tablets for Relapsing-Remitting Multiple Sclerosis: A Clinician’s Review. Neurol Ther. 2022; 11(2): 571-95. http://doi.org/10.1007/s40120-022-00339-7.
2. Leist TP, Weissert R. Cladribine: mode of action and implications for treatment of multiple sclerosis. Clin Neuropharmacol. 2011; 34(1): 28-35.
3. Bar-Or A, Li R. Cellular immunology of relapsing multiple sclerosis: interactions, checks, and balances. Lancet Neurol. 2021; 20(6): 470-83.
4. Zhang X, Tao Y, Chopra M et al. Differential reconstitution of T cell subsets following immunodepleting treatment with alemtuzumab (anti-CD52 monoclonal antibody) in patients with relapsing-remitting multiple sclerosis. J Immunol. 2013; 191(12): 5867-74.
5. Baker D, Herrod SS, Alvarez-Gonzalez C et al. Both cladribine and alemtuzumab may effect MS via B-cell depletion. Neurol Neuroimmunol Neuroinflamm. 2017; 4(4): e360.
6. Comi G, Cook S, Giovannoni G et al. Effect of cladribine tablets on lymphocyte reduction and repopulation dynamics in patients with relapsing multiple sclerosis. Mult Scler Relat Disord. 2019; 29: 168-74. http://doi.org/10.1016/j.msard.2019.01.038.
7. Ceronie B, Jacobs BM, Baker D et al. Cladribine treatment of multiple sclerosis is associated with depletion of memory B cells. J Neurol. 2018; 265(5): 1199-209. http://doi.org/10.1007/s00415-018-8830-y.
8. Sellner J, Rommer PS. Immunological consequences of „immune reconstitution therapy” in multiple sclerosis: A systematic review. Autoimmun Rev. 2020; 19(4): 102492. http://doi.org/10.1016/j.autrev.2020.102492.
9. Wiendl H, Schmierer K, Hodgkinson S et al.; MAGNIFY-MS Study Group. Specific Patterns of Immune Cell Dynamics May Explain the Early Onset and Prolonged Efficacy of Cladribine Tablets: A MAGNIFY-MS Substudy. Neurol Neuroimmunol Neuroinflamm. 2022; 10(1): e200048.
10. Lycett MJ, Lea RA, Maltby VE et al. The effect of cladribine on immunoglobulin levels compared to B cell targeting therapies in multiple sclerosis. Mult Scler J Exp Transl Clin. 2023; 9(1): 20552173221149688. http://doi.org/10.1177/20552173221149688.
11. Giunti D, Borsellino G, Benelli R et al. Phenotypic and functional analysis of T cells homing into the CSF of subjects with inflammatory diseases of the CNS. J Leukoc Biol. 2003; 73(5): 584-90. http://doi.org/10.1189/jlb.1202598.
12. Kivisäkk P, Mahad DJ, Callahan MK et al. Expression of CCR7 in multiple sclerosis: impli-cations for CNS immunity. Ann Neurol. 2004; 55(5): 627-38. http://doi.org/10.1002/ana.20049.
13. Stuve O, Soelberg Soerensen P, Leist T et al. Effects of cladribine tablets on lymphocyte subsets in patients with multiple sclerosis: an extended analysis of surface markers. Ther Adv Neurol Disord. 2019; 12: 1756286419854986. http://doi.org/10.1177/1756286419854986.
14. Mitosek-Szewczyk K, Tabarkiewicz J, Wilczynska B et al. Impact of cladribine therapy on changes in circulating dendritic cell subsets, T cells and B cells in patients with multiple scle-rosis. J Neurol Sci. 2013; 332(1-2): 35-40. http://doi.org/10.1016/j.jns.2013.06.003.
15. Liliemark J. The clinical pharmacokinetics of cladribine. Clin Pharmacokinet. 1997; 32(2): 120-31. http://doi.org/10.2165/00003088-199732020-00003.
2. Leist TP, Weissert R. Cladribine: mode of action and implications for treatment of multiple sclerosis. Clin Neuropharmacol. 2011; 34(1): 28-35.
3. Bar-Or A, Li R. Cellular immunology of relapsing multiple sclerosis: interactions, checks, and balances. Lancet Neurol. 2021; 20(6): 470-83.
4. Zhang X, Tao Y, Chopra M et al. Differential reconstitution of T cell subsets following immunodepleting treatment with alemtuzumab (anti-CD52 monoclonal antibody) in patients with relapsing-remitting multiple sclerosis. J Immunol. 2013; 191(12): 5867-74.
5. Baker D, Herrod SS, Alvarez-Gonzalez C et al. Both cladribine and alemtuzumab may effect MS via B-cell depletion. Neurol Neuroimmunol Neuroinflamm. 2017; 4(4): e360.
6. Comi G, Cook S, Giovannoni G et al. Effect of cladribine tablets on lymphocyte reduction and repopulation dynamics in patients with relapsing multiple sclerosis. Mult Scler Relat Disord. 2019; 29: 168-74. http://doi.org/10.1016/j.msard.2019.01.038.
7. Ceronie B, Jacobs BM, Baker D et al. Cladribine treatment of multiple sclerosis is associated with depletion of memory B cells. J Neurol. 2018; 265(5): 1199-209. http://doi.org/10.1007/s00415-018-8830-y.
8. Sellner J, Rommer PS. Immunological consequences of „immune reconstitution therapy” in multiple sclerosis: A systematic review. Autoimmun Rev. 2020; 19(4): 102492. http://doi.org/10.1016/j.autrev.2020.102492.
9. Wiendl H, Schmierer K, Hodgkinson S et al.; MAGNIFY-MS Study Group. Specific Patterns of Immune Cell Dynamics May Explain the Early Onset and Prolonged Efficacy of Cladribine Tablets: A MAGNIFY-MS Substudy. Neurol Neuroimmunol Neuroinflamm. 2022; 10(1): e200048.
10. Lycett MJ, Lea RA, Maltby VE et al. The effect of cladribine on immunoglobulin levels compared to B cell targeting therapies in multiple sclerosis. Mult Scler J Exp Transl Clin. 2023; 9(1): 20552173221149688. http://doi.org/10.1177/20552173221149688.
11. Giunti D, Borsellino G, Benelli R et al. Phenotypic and functional analysis of T cells homing into the CSF of subjects with inflammatory diseases of the CNS. J Leukoc Biol. 2003; 73(5): 584-90. http://doi.org/10.1189/jlb.1202598.
12. Kivisäkk P, Mahad DJ, Callahan MK et al. Expression of CCR7 in multiple sclerosis: impli-cations for CNS immunity. Ann Neurol. 2004; 55(5): 627-38. http://doi.org/10.1002/ana.20049.
13. Stuve O, Soelberg Soerensen P, Leist T et al. Effects of cladribine tablets on lymphocyte subsets in patients with multiple sclerosis: an extended analysis of surface markers. Ther Adv Neurol Disord. 2019; 12: 1756286419854986. http://doi.org/10.1177/1756286419854986.
14. Mitosek-Szewczyk K, Tabarkiewicz J, Wilczynska B et al. Impact of cladribine therapy on changes in circulating dendritic cell subsets, T cells and B cells in patients with multiple scle-rosis. J Neurol Sci. 2013; 332(1-2): 35-40. http://doi.org/10.1016/j.jns.2013.06.003.
15. Liliemark J. The clinical pharmacokinetics of cladribine. Clin Pharmacokinet. 1997; 32(2): 120-31. http://doi.org/10.2165/00003088-199732020-00003.