B cell depletion attenuates CD27 signaling of T helper cells in multiple sclerosis

Ulutekin, Can; Galli, Edoardo; Schreiner, Bettina; Khademi, Mohsen; Callegari, Ilaria; Piehl, Fredrik; Sanderson, Nicholas; Kirschenbaum, Daniel; Mundt, Sarah; Filippi, Massimo; Furlan, Roberto; Olsson, Tomas; Derfuss, Tobias; Ingelfinger, Florian; Becher, Burkhard

doi:10.1016/j.xcrm.2023.101351

Cited by 2 publications

(2 citation statements)

References 87 publications

(112 reference statements)

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“…This supports the theory that anti-CD20 agents deplete B cells that have potential crosstalk with T cell subsets ( 10 , 24 , 25 ). A significant decrease in the frequency of cTfh cells has been observed in multiple sclerosis patients following BCDT treatment, and this reduction has been associated with disease remission ( 26 ). These observations suggest that BCDTs may indirectly deplete potentially pathogenic cTfh cells, highlighting their interdependence with B cells.…”

Section: Discussionmentioning

confidence: 99%

Normalized circulating Tfh and Th17 associates with improvement in myasthenia gravis treated with ofatumumab

Song,

He,

Huo

et al. 2024

Front. Immunol.

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ObjectiveTo assess the effect of B cell depletion therapy (BCDT) on circulating T follicular helper (cTfh) and circulating T helper 17 (cTh17) cells and its relation to clinical improvement in patients with myasthenia gravis (MG).Methods28 anti-AchR positive MG patients treated with ofatumumab and 28 healthy controls (HCs) were included. Frequencies of cTfh and cTh17 cells were monitored by flow cytometry at baseline and 4, and 12 weeks after the initial dose ofatumumab. Serum cytokines associated with cTfh and cTh17, including IL-6, IL-21, and IL-17, were also analyzed.ResultsThe frequency of cTfh and cTh17 significantly increased in MG patients compared with HCs. Additionally, elevated levels of both T-cell subsets correlated with MG severity. During the follow-up, cTfh and cTh17 return to normal after BCDT. Furthermore, the decrease in cTfh and cTh17 was associated with MG scores improvement over time. Notably, cTfh- and cTh17-related cytokines, including IL-6, IL-21, and IL-17, exhibited a marked decrease following ofatumumab therapy.ConclusionsAbnormal expansion of cTfh and cTh17 cells may be key features in the immunopathology of MG. Their levels returned to normal after BCDT, which was closely correlated with clinical amelioration. This result suggests that these two T-cell subsets may be targets for BCDT treatment of MG.

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Section: Discussionmentioning

confidence: 99%

Normalized circulating Tfh and Th17 associates with improvement in myasthenia gravis treated with ofatumumab

Song,

He,

Huo

et al. 2024

Front. Immunol.

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“… 4 B cell-depleting agents have been highly efficient in the treatment of MS, although functional understanding of their contribution to disease remains largely enigmatic. 5 Thus, we discerned genetic predisposition from non-heritable, disease-related effects on the circulating B cell compartment in monozygotic twin pairs discordant for MS.…”

Section: Introductionmentioning

confidence: 97%

Twin study dissects CXCR3+ memory B cells as non-heritable feature in multiple sclerosis

Ingelfinger,

Kuiper,

Ulutekin

et al. 2024

Med

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B cell depletion attenuates CD27 signaling of T helper cells in multiple sclerosis

Cited by 2 publications

References 87 publications

Normalized circulating Tfh and Th17 associates with improvement in myasthenia gravis treated with ofatumumab

Normalized circulating Tfh and Th17 associates with improvement in myasthenia gravis treated with ofatumumab

Twin study dissects CXCR3+ memory B cells as non-heritable feature in multiple sclerosis

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