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

Scientific paper - Original scientific paper

• Author: Simona Rolla
• Author: Stefania Federica De Mercanti
• Author: Valentina Bardina
• Author: Alessandro Maglione
• Author: Daniela Taverna
• Author: Francesco Novelli
• Author: Eleonora Cocco
• Author: Anton Vladić
• Author: Mario Habek
• Author: Ivan Adamec
• Author: Pietro Osvaldo Luigi Annovazzi
• Author: Dana Horakova
• Author: Marinella Clerico
• Author's institution: University of Zagreb; School of Medicine; (Department of Neurology)
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Neurology

Abstract (english)

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.
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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).
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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.
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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.

• Keywords (english): Alemtuzumab / pharmacology; Alemtuzumab / therapeutic use; CD4-Positive T-Lymphocytes; Follow-Up Studies; Humans; Multiple Sclerosis / drug therapy; RNA, Messenger / therapeutic use
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Published version
• Journal title: Frontiers in Immunology
• Numbering: vol. 13, 818325
• e-ISSN: 1664-3224
• DOI: https://doi.org/10.3389/fimmu.2022.818325
• URN:NBN: urn:nbn:hr:105:992905
• Publication: 2022-02-28
• Document URL: https://www.frontiersin.org/articles/10.3389/fimmu.2022.818325/full
• Type of resource: Text
• Access conditions: Open access
• Created on: 2022-09-30 09:40:14