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Long-Term Effects of Alemtuzumab on CD4+ Lymphocytes in Multiple Sclerosis Patients: A 72-Month Follow-Up

S. Rolla, SF. De Mercanti, V. Bardina, A. Maglione, D. Taverna, F. Novelli, E. Cocco, A. Vladic, M. Habek, I. Adamec, POL. Annovazzi, D. Horakova, M. Clerico

. 2022 ; 13 (-) : 818325. [pub] 20220228

Jazyk angličtina Země Švýcarsko

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc22019348

Introduction: Alemtuzumab is highly effective in the treatment of patients with relapsing multiple sclerosis (PwRMS) and selectively targets the CD52 antigen, with a consequent profound lymphopenia, particularly of CD4+ T lymphocytes. However, the immunological basis of its long-term efficacy has not been clearly elucidated. Methods: We followed up 29 alemtuzumab-treated RMS patients over a period of 72 months and studied the immunological reconstitution of their CD4+ T cell subsets by means of phenotypic and functional analysis and through mRNA-related molecule expression, comparing them to healthy subject (HS) values (rate 2:1). Results: In patients receiving only two-course alemtuzumab, the percentage of CD4+ lymphocytes decreased and returned to basal levels only at month 48. Immune reconstitution of the CD4+ subsets was characterized by a significant increase (p < 0.001) in Treg cell percentage at month 24, when compared to baseline, and was accompanied by restoration of the Treg suppressor function that increased within a range from 2- to 6.5-fold compared to baseline and that persisted through to the end of the follow-up. Furthermore, a significant decrease in self-reactive myelin basic protein-specific Th17 (p < 0.0001) and Th1 (p < 0.05) cells reaching HS values was observed starting from month 12. There was a change in mRNA of cytokines, chemokines, and transcriptional factors related to Th17, Th1, and Treg cell subset changes, consequently suggesting a shift toward immunoregulation and a reduction of T cell recruitment to the central nervous system. Conclusions: These data provide further insight into the mechanism that could contribute to the long-term 6-year persistence of the clinical effect of alemtuzumab on RMS disease activity.

Citace poskytuje Crossref.org

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$a Introduction: Alemtuzumab is highly effective in the treatment of patients with relapsing multiple sclerosis (PwRMS) and selectively targets the CD52 antigen, with a consequent profound lymphopenia, particularly of CD4+ T lymphocytes. However, the immunological basis of its long-term efficacy has not been clearly elucidated. Methods: We followed up 29 alemtuzumab-treated RMS patients over a period of 72 months and studied the immunological reconstitution of their CD4+ T cell subsets by means of phenotypic and functional analysis and through mRNA-related molecule expression, comparing them to healthy subject (HS) values (rate 2:1). Results: In patients receiving only two-course alemtuzumab, the percentage of CD4+ lymphocytes decreased and returned to basal levels only at month 48. Immune reconstitution of the CD4+ subsets was characterized by a significant increase (p < 0.001) in Treg cell percentage at month 24, when compared to baseline, and was accompanied by restoration of the Treg suppressor function that increased within a range from 2- to 6.5-fold compared to baseline and that persisted through to the end of the follow-up. Furthermore, a significant decrease in self-reactive myelin basic protein-specific Th17 (p < 0.0001) and Th1 (p < 0.05) cells reaching HS values was observed starting from month 12. There was a change in mRNA of cytokines, chemokines, and transcriptional factors related to Th17, Th1, and Treg cell subset changes, consequently suggesting a shift toward immunoregulation and a reduction of T cell recruitment to the central nervous system. Conclusions: These data provide further insight into the mechanism that could contribute to the long-term 6-year persistence of the clinical effect of alemtuzumab on RMS disease activity.
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$a De Mercanti, Stefania Federica $u Department of Clinical and Biological Sciences, University of Torino, Torino, Italy
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$a Bardina, Valentina $u Department of Clinical and Biological Sciences, University of Torino, Torino, Italy $u Laboratory of Microbiology and Virology, Amedeo di Savoia Hospital, Torino, Italy
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$a Maglione, Alessandro $u Department of Clinical and Biological Sciences, University of Torino, Torino, Italy
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$a Taverna, Daniela $u Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy
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$a Novelli, Francesco $u Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy
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$a Cocco, Eleonora $u Department of Medical Science and Public Health, University of Cagliari and Multiple Sclerosis Center, Cagliari, Italy
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$a Vladic, Anton $u Department of Neurology, Clinical Hospital Sveti Duh Zagreb and Medical Faculty, University J.J Strossmayer Osijek, Prague, Croatia
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$a Habek, Mario $u Referral Center for Autonomic Nervous System, University Hospital Center Zagreb, Zagreb, Croatia $u School of Medicine, University of Zagreb, Zagreb, Croatia
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$a Adamec, Ivan $u Referral Center for Autonomic Nervous System, University Hospital Center Zagreb, Zagreb, Croatia $u School of Medicine, University of Zagreb, Zagreb, Croatia
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$a Annovazzi, Pietro Osvaldo Luigi $u Multiple Sclerosis Centre, Gallarate Hospital, ASST Valle Olona, Gallarate, Italy
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$a Horakova, Dana $u Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czechia
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$a Clerico, Marinella $u Department of Clinical and Biological Sciences, University of Torino, Torino, Italy
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