Ocrelizumab Alters Cytotoxic Lymphocyte Function While Reducing EBV-Specific CD8


Journal

Neurology(R) neuroimmunology & neuroinflammation
ISSN: 2332-7812
Titre abrégé: Neurol Neuroimmunol Neuroinflamm
Pays: United States
ID NLM: 101636388

Informations de publication

Date de publication:
Jul 2024
Historique:
medline: 25 4 2024
pubmed: 25 4 2024
entrez: 25 4 2024
Statut: ppublish

Résumé

The role of B cells in the pathogenic events leading to relapsing multiple sclerosis (R-MS) has only been recently elucidated. A pivotal step in defining this role has been provided by therapeutic efficacy of anti-CD20 monoclonal antibodies. Indeed, treatment with anti-CD20 can also alter number and function of other immune cells not directly expressing CD20 on their cell surface, whose activities can contribute to unknown aspects influencing therapeutic efficacy. We examined the phenotype and function of cytotoxic lymphocytes and Epstein-Barr virus (EBV)-specific immune responses in people with R-MS before and after ocrelizumab treatment. In this prospective study, we collected blood samples from people with R-MS (n = 41) before and 6 and 12 months after initiating ocrelizumab to assess the immune phenotype and the indirect impact on cytotoxic functions of CD8 We observed that while ocrelizumab depleted circulating B cells, it also reduced the expression of activation and migratory markers on both CD8 Taken together, our findings suggest that ocrelizumab-while depleting B cells-affects the cytotoxic function of CD8

Sections du résumé

BACKGROUND AND OBJECTIVES OBJECTIVE
The role of B cells in the pathogenic events leading to relapsing multiple sclerosis (R-MS) has only been recently elucidated. A pivotal step in defining this role has been provided by therapeutic efficacy of anti-CD20 monoclonal antibodies. Indeed, treatment with anti-CD20 can also alter number and function of other immune cells not directly expressing CD20 on their cell surface, whose activities can contribute to unknown aspects influencing therapeutic efficacy. We examined the phenotype and function of cytotoxic lymphocytes and Epstein-Barr virus (EBV)-specific immune responses in people with R-MS before and after ocrelizumab treatment.
METHODS METHODS
In this prospective study, we collected blood samples from people with R-MS (n = 41) before and 6 and 12 months after initiating ocrelizumab to assess the immune phenotype and the indirect impact on cytotoxic functions of CD8
RESULTS RESULTS
We observed that while ocrelizumab depleted circulating B cells, it also reduced the expression of activation and migratory markers on both CD8
DISCUSSION CONCLUSIONS
Taken together, our findings suggest that ocrelizumab-while depleting B cells-affects the cytotoxic function of CD8

Identifiants

pubmed: 38662990
doi: 10.1212/NXI.0000000000200250
doi:

Substances chimiques

Antibodies, Monoclonal, Humanized 0
ocrelizumab A10SJL62JY
Immunologic Factors 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e200250

Auteurs

Gianmarco Abbadessa (G)

From the Department of Advanced Medical and Surgical Sciences (G.A., G. Miele, E.S., G.L., S. Bonavita), University of Campania Luigi Vanvitelli; Istituto per l'Endocrinologia e l'Oncologia Sperimentale "G.Salvatore" - Consiglio Nazionale delle Ricerche (M.T.L., S. Bruzzaniti, G. Matarese, M.G.); Department of Molecular Medicine and Medical Biotechnologies (E.P., G. Matarese, M.G.); Department of Clinical Medicine and Surgery (F.P.), University of Naples "Federico II"; and UOC Biochimica Clinica - Ospedali dei Colli (C.D.F.), Naples, Italy.

Maria Teresa Lepore (MT)

From the Department of Advanced Medical and Surgical Sciences (G.A., G. Miele, E.S., G.L., S. Bonavita), University of Campania Luigi Vanvitelli; Istituto per l'Endocrinologia e l'Oncologia Sperimentale "G.Salvatore" - Consiglio Nazionale delle Ricerche (M.T.L., S. Bruzzaniti, G. Matarese, M.G.); Department of Molecular Medicine and Medical Biotechnologies (E.P., G. Matarese, M.G.); Department of Clinical Medicine and Surgery (F.P.), University of Naples "Federico II"; and UOC Biochimica Clinica - Ospedali dei Colli (C.D.F.), Naples, Italy.

Sara Bruzzaniti (S)

From the Department of Advanced Medical and Surgical Sciences (G.A., G. Miele, E.S., G.L., S. Bonavita), University of Campania Luigi Vanvitelli; Istituto per l'Endocrinologia e l'Oncologia Sperimentale "G.Salvatore" - Consiglio Nazionale delle Ricerche (M.T.L., S. Bruzzaniti, G. Matarese, M.G.); Department of Molecular Medicine and Medical Biotechnologies (E.P., G. Matarese, M.G.); Department of Clinical Medicine and Surgery (F.P.), University of Naples "Federico II"; and UOC Biochimica Clinica - Ospedali dei Colli (C.D.F.), Naples, Italy.

Erica Piemonte (E)

From the Department of Advanced Medical and Surgical Sciences (G.A., G. Miele, E.S., G.L., S. Bonavita), University of Campania Luigi Vanvitelli; Istituto per l'Endocrinologia e l'Oncologia Sperimentale "G.Salvatore" - Consiglio Nazionale delle Ricerche (M.T.L., S. Bruzzaniti, G. Matarese, M.G.); Department of Molecular Medicine and Medical Biotechnologies (E.P., G. Matarese, M.G.); Department of Clinical Medicine and Surgery (F.P.), University of Naples "Federico II"; and UOC Biochimica Clinica - Ospedali dei Colli (C.D.F.), Naples, Italy.

Giuseppina Miele (G)

From the Department of Advanced Medical and Surgical Sciences (G.A., G. Miele, E.S., G.L., S. Bonavita), University of Campania Luigi Vanvitelli; Istituto per l'Endocrinologia e l'Oncologia Sperimentale "G.Salvatore" - Consiglio Nazionale delle Ricerche (M.T.L., S. Bruzzaniti, G. Matarese, M.G.); Department of Molecular Medicine and Medical Biotechnologies (E.P., G. Matarese, M.G.); Department of Clinical Medicine and Surgery (F.P.), University of Naples "Federico II"; and UOC Biochimica Clinica - Ospedali dei Colli (C.D.F.), Naples, Italy.

Elisabetta Signoriello (E)

From the Department of Advanced Medical and Surgical Sciences (G.A., G. Miele, E.S., G.L., S. Bonavita), University of Campania Luigi Vanvitelli; Istituto per l'Endocrinologia e l'Oncologia Sperimentale "G.Salvatore" - Consiglio Nazionale delle Ricerche (M.T.L., S. Bruzzaniti, G. Matarese, M.G.); Department of Molecular Medicine and Medical Biotechnologies (E.P., G. Matarese, M.G.); Department of Clinical Medicine and Surgery (F.P.), University of Naples "Federico II"; and UOC Biochimica Clinica - Ospedali dei Colli (C.D.F.), Naples, Italy.

Francesco Perna (F)

From the Department of Advanced Medical and Surgical Sciences (G.A., G. Miele, E.S., G.L., S. Bonavita), University of Campania Luigi Vanvitelli; Istituto per l'Endocrinologia e l'Oncologia Sperimentale "G.Salvatore" - Consiglio Nazionale delle Ricerche (M.T.L., S. Bruzzaniti, G. Matarese, M.G.); Department of Molecular Medicine and Medical Biotechnologies (E.P., G. Matarese, M.G.); Department of Clinical Medicine and Surgery (F.P.), University of Naples "Federico II"; and UOC Biochimica Clinica - Ospedali dei Colli (C.D.F.), Naples, Italy.

Chiara De Falco (C)

From the Department of Advanced Medical and Surgical Sciences (G.A., G. Miele, E.S., G.L., S. Bonavita), University of Campania Luigi Vanvitelli; Istituto per l'Endocrinologia e l'Oncologia Sperimentale "G.Salvatore" - Consiglio Nazionale delle Ricerche (M.T.L., S. Bruzzaniti, G. Matarese, M.G.); Department of Molecular Medicine and Medical Biotechnologies (E.P., G. Matarese, M.G.); Department of Clinical Medicine and Surgery (F.P.), University of Naples "Federico II"; and UOC Biochimica Clinica - Ospedali dei Colli (C.D.F.), Naples, Italy.

G Lus (G)

From the Department of Advanced Medical and Surgical Sciences (G.A., G. Miele, E.S., G.L., S. Bonavita), University of Campania Luigi Vanvitelli; Istituto per l'Endocrinologia e l'Oncologia Sperimentale "G.Salvatore" - Consiglio Nazionale delle Ricerche (M.T.L., S. Bruzzaniti, G. Matarese, M.G.); Department of Molecular Medicine and Medical Biotechnologies (E.P., G. Matarese, M.G.); Department of Clinical Medicine and Surgery (F.P.), University of Naples "Federico II"; and UOC Biochimica Clinica - Ospedali dei Colli (C.D.F.), Naples, Italy.

Giuseppe Matarese (G)

From the Department of Advanced Medical and Surgical Sciences (G.A., G. Miele, E.S., G.L., S. Bonavita), University of Campania Luigi Vanvitelli; Istituto per l'Endocrinologia e l'Oncologia Sperimentale "G.Salvatore" - Consiglio Nazionale delle Ricerche (M.T.L., S. Bruzzaniti, G. Matarese, M.G.); Department of Molecular Medicine and Medical Biotechnologies (E.P., G. Matarese, M.G.); Department of Clinical Medicine and Surgery (F.P.), University of Naples "Federico II"; and UOC Biochimica Clinica - Ospedali dei Colli (C.D.F.), Naples, Italy.

Simona Bonavita (S)

From the Department of Advanced Medical and Surgical Sciences (G.A., G. Miele, E.S., G.L., S. Bonavita), University of Campania Luigi Vanvitelli; Istituto per l'Endocrinologia e l'Oncologia Sperimentale "G.Salvatore" - Consiglio Nazionale delle Ricerche (M.T.L., S. Bruzzaniti, G. Matarese, M.G.); Department of Molecular Medicine and Medical Biotechnologies (E.P., G. Matarese, M.G.); Department of Clinical Medicine and Surgery (F.P.), University of Naples "Federico II"; and UOC Biochimica Clinica - Ospedali dei Colli (C.D.F.), Naples, Italy.

Mario Galgani (M)

From the Department of Advanced Medical and Surgical Sciences (G.A., G. Miele, E.S., G.L., S. Bonavita), University of Campania Luigi Vanvitelli; Istituto per l'Endocrinologia e l'Oncologia Sperimentale "G.Salvatore" - Consiglio Nazionale delle Ricerche (M.T.L., S. Bruzzaniti, G. Matarese, M.G.); Department of Molecular Medicine and Medical Biotechnologies (E.P., G. Matarese, M.G.); Department of Clinical Medicine and Surgery (F.P.), University of Naples "Federico II"; and UOC Biochimica Clinica - Ospedali dei Colli (C.D.F.), Naples, Italy.

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