Evidence map›Paper›PMID 42312812›Full record

ArticleAnnals of neurology2026

From Marginal to Central: Marginal Zone-like B Cells as Critical Targets in Cladribine-Treated Multiple Sclerosis.

Marta Pirronello, Mario Picozza, Gisella Guerrera, Silvia Corbisiero, Andrea Misiti, Roberta C Placido, Alice Verdiani, Lorenzo de Marco, Manolo Sambucci, Elena Olivieri and 11 more

Abstract read
In one paragraph

Article in Annals of neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors.

Marta Pirronello *Neuroimmunology Unit, European Centre for Brain Research, Fondazione Santa Lucia IRCCS, Rome, Italy.ORCID https://orcid.org/0000-0002-9907-2279
Mario Picozza *Neuroimmunology Unit, European Centre for Brain Research, Fondazione Santa Lucia IRCCS, Rome, Italy.ORCID https://orcid.org/0000-0002-2529-6456
Gisella GuerreraNeuroimmunology Unit, European Centre for Brain Research, Fondazione Santa Lucia IRCCS, Rome, Italy.ORCID https://orcid.org/0000-0002-3467-6469
Silvia CorbisieroNeuroimmunology Unit, European Centre for Brain Research, Fondazione Santa Lucia IRCCS, Rome, Italy.ORCID https://orcid.org/0000-0001-7360-6570
Andrea MisitiNeuroimmunology Unit, European Centre for Brain Research, Fondazione Santa Lucia IRCCS, Rome, Italy.ORCID https://orcid.org/0009-0002-5019-5400
Roberta C PlacidoNeuroimmunology Unit, European Centre for Brain Research, Fondazione Santa Lucia IRCCS, Rome, Italy.ORCID https://orcid.org/0000-0001-6083-8292
Alice VerdianiNeuroimmunology Unit, European Centre for Brain Research, Fondazione Santa Lucia IRCCS, Rome, Italy.ORCID https://orcid.org/0000-0001-9367-9574
Lorenzo de MarcoNeuroimmunology Unit, European Centre for Brain Research, Fondazione Santa Lucia IRCCS, Rome, Italy.ORCID https://orcid.org/0000-0002-4995-9752
Manolo SambucciNeuroimmunology Unit, European Centre for Brain Research, Fondazione Santa Lucia IRCCS, Rome, Italy.ORCID https://orcid.org/0000-0003-1124-7327
Elena OlivieriNeuroimmunology Unit, European Centre for Brain Research, Fondazione Santa Lucia IRCCS, Rome, Italy.ORCID https://orcid.org/0009-0003-6236-7975
Daniela F AngeliniNeuroimmunology Unit, European Centre for Brain Research, Fondazione Santa Lucia IRCCS, Rome, Italy.ORCID https://orcid.org/0000-0003-4552-9226
Esmeralda QuartuccioNeuroscience Department, San Camillo-Forlanini Hospital, Rome, Italy.
Luca ProsperiniNeuroscience Department, San Camillo-Forlanini Hospital, Rome, Italy.ORCID https://orcid.org/0000-0003-3237-6267
Carla TortorellaNeuroscience Department, San Camillo-Forlanini Hospital, Rome, Italy.ORCID https://orcid.org/0000-0001-9037-7300
Maria C BuscarinuDepartment of Neurosciences, Mental Health and Sensory Organs, Sapienza University of Rome, Rome, Italy.ORCID https://orcid.org/0000-0002-4839-1528
Valeria ZancanDepartment of Neurosciences, Mental Health and Sensory Organs, Sapienza University of Rome, Rome, Italy.ORCID https://orcid.org/0009-0004-3948-2534
Francesca de MasiNeuroimaging Unit, Fondazione Santa Lucia IRCSS, Rome, Italy.
Marco SalvettiDepartment of Neurosciences, Mental Health and Sensory Organs, Sapienza University of Rome, Rome, Italy.ORCID https://orcid.org/0000-0002-0501-8803
Claudio GasperiniNeuroscience Department, San Camillo-Forlanini Hospital, Rome, Italy.ORCID https://orcid.org/0000-0002-3959-4067
Giovanna BorsellinoNeuroimmunology Unit, European Centre for Brain Research, Fondazione Santa Lucia IRCCS, Rome, Italy.ORCID https://orcid.org/0000-0002-4227-6481
Luca BattistiniNeuroimmunology Unit, European Centre for Brain Research, Fondazione Santa Lucia IRCCS, Rome, Italy.ORCID https://orcid.org/0000-0002-6488-4891

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveMultiple sclerosis (MS) is a chronic autoimmune disease where B cells play a central pathogenic role. Cladribine, an oral therapy, provides durable benefits by reshaping lymphocyte populations, yet its specific long-term impact on distinct B-cell subsets is not fully understood. This study aimed to define cladribine's longitudinal effects on B-cell subsets and characterize their inflammatory properties.

methodsWe conducted a 48-month longitudinal study of 36 persons with relapsing-remitting MS treated with cladribine who had completed 2 annual treatment cycles, using high-parameter flow cytometry to track B-cell subset dynamics. In a parallel cross-sectional analysis, B cells from 16 untreated patients and 16 healthy donors were profiled for polyfunctional cytokine production granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and key surface markers.

resultsCladribine induced profound, sustained depletion of memory B cells, with marginal zone-like (MZ-like) cells showing the deepest and most persistent loss, alongside reconstitution of transitional and naïve populations. Functionally, MZ-like B cells were the most potent polyfunctional producers of proinflammatory cytokines and immunoglobulin M (IgM), a capacity significantly enhanced in persons with MS compared to healthy donors, and expressed the highest levels of CD1c and CD1d, consistent with specialization in lipid antigen presentation.

interpretationMZ-like B cells are a dominant, polyfunctional inflammatory subset in MS, equipped for non-canonical lipid antigen presentation and IgM secretion. They represent a preferential pharmacological target of cladribine. Sustained reduction of this pathogenic memory pool, followed by repopulation with less inflammatory B cells, offers a mechanistic basis for cladribine's durable clinical benefit and nominates MZ-like cells as biomarkers of response and therapeutic targets. ANN NEUROL 2026;100:808-823.

Indexed as

B-LymphocytesB-Lymphocyte SubsetsCladribineImmunosuppressive AgentsMultiple Sclerosis, Relapsing-RemittingAdultCross-Sectional StudiesCytokinesFemaleHumansLongitudinal StudiesMaleMiddle AgedCladribineCytokinesImmunosuppressive Agents

Identifiers

PMID42312812
PMCPMC13587114

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.