Immune reconstitution therapies: concepts for durable remission in multiple sclerosis

Lünemann, Jan D.; Ruck, Tobias; Muraro, Paolo A.; Bar‐Or, Amit; Wiendl, Heinz

doi:10.1038/s41582-019-0268-z

Cited by 79 publications

(99 citation statements)

References 88 publications

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“…The impact on memory B cells was similar to the depletion rates found after treatment with injectable CLAD 15 and has been implicated in the long-lasting efficacy of IRTs. 1,9,16,17 We also confirm a selectivity of CLAD towards central memory TH cells. Importantly, a majority of autoreactive cells belong to this very phenotype.…”

Section: Discussionsupporting

confidence: 73%

Long‐term peripheral immune cell profiling reveals further targets of oral cladribine in MS

Moser

Schwenker

Seiberl

et al. 2020

Ann Clin Transl Neurol

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Objectives: To expand the knowledge about the immunological consequences of cladribine (CLAD), a pulsed immune reconstitution therapy approved for active multiple sclerosis (MS), beyond the known short-term effects on peripheral immune cell subsets. Methods: In this study, we characterized depletion and restitution kinetics as well as cytokine profiles of peripheral immune cell subsets in 18 patients with MS following treatment with oral CLAD. The methods involved blood collection prior to CLAD and every three months over a period of 24 months, and extensive characterization of various immune cells subsets by multiparametric flow cytometry. Results: We found a selectivity of CLAD towards central memory T cells and memory B cells and detected a hyper-repopulation of maturing B cells. Counts of classical (À65%) and various nonclassical TH17 cells (À84% to À87%) were markedly reduced 24 months after treatment start, and were comparable with depletion rates of classswitched memory B-cell phenotypes (À87% to À95%). The nadir of TH cells was more pronounced in the second treatment year. We observed a proportional surge of CD20 T-cell subsets and an expansion of regulatory T, B and NK cells. Natural killer T cells (NKT) were only depleted in year two and did not recover. Interpretation: Peripheral immune cell profiling revealed more differentiated insights into the immunological effects of CLAD. While some immune cell subsets expanded, we also observed additive depleting effects after the second treatment course. Further studies are required to elucidate whether these changes are paramount for the consistent and prolonged disease-modifying effect of CLAD.

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Section: Discussionsupporting

confidence: 73%

Long‐term peripheral immune cell profiling reveals further targets of oral cladribine in MS

Moser

Schwenker

Seiberl

et al. 2020

Ann Clin Transl Neurol

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“…Alemtuzumab. Alemtuzumab is a monoclonal antibody to CD52 that leads to depletion of T cells and B cells 99,100 . Treatment impairs cellular and humoral immunity; the extent of impairment depends on the time since the last dose and the number of treatment cycles 101,102 .…”

Section: Immune-depleting and Repopulating Therapies B Cell-depletingmentioning

confidence: 99%

Neurological immunotherapy in the era of COVID-19 — looking for consensus in the literature

Korsukewitz¹,

Reddel

Bar‐Or

et al. 2020

Nat Rev Neurol

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“…Immune reconstitution therapy (IRT) is an emerging concept for the treatment of MS [9,10]. The aim of IRTs is to eliminate a pathogenic immune repertoire through intense short-term immunosuppression, and to subsequently rebuild a new and healthy immune system with the goal to re-establish a persistent immune tolerance [11]. After a period of deep immune depletion, the immune system undergoes reconstitution and radical changes in the lymphocyte repertoire and regains its ability to respond to infections.…”

Section: Introductionmentioning

confidence: 99%

The Meaning of Immune Reconstitution after Alemtuzumab Therapy in Multiple Sclerosis

Rolla

Maglione

Mercanti

et al. 2020

Cells

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Alemtuzumab is a monoclonal antibody that binds to CD52, a protein present on the surface of mature lymphocytes, but not on the stem cells from which these lymphocytes are derived. It is currently used as an immune reconstitution therapy in patients with relapsing–remitting multiple sclerosis. Alemtuzumab treatment is an intermittent infusion that induces long-term remission of Multiple Sclerosis also in the treatment-free period. After the robust T and B cell depletion induced by alemtuzumab, the immune system undergoes radical changes during its reconstitution. In this review, we will discuss the current knowledge on the reconstitution of the lymphocyte repertoire after alemtuzumab treatment and how it could affect the development of side effects, which led to its temporary suspension by the European Medical Agency.

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Immune reconstitution therapies: concepts for durable remission in multiple sclerosis

Cited by 79 publications

References 88 publications

Long‐term peripheral immune cell profiling reveals further targets of oral cladribine in MS

Long‐term peripheral immune cell profiling reveals further targets of oral cladribine in MS

Neurological immunotherapy in the era of COVID-19 — looking for consensus in the literature

The Meaning of Immune Reconstitution after Alemtuzumab Therapy in Multiple Sclerosis

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