Evidence map›Paper›PMID 38556899›Full record

SynthesisEuropean journal of neurology2024

Beyond T cell toxicity - Intrathecal chemokine CXCL13 indicating B cell involvement in immune-related adverse events following checkpoint inhibition: A two-case series and literature review.

Ferdinand Otto, Michael Seiberl, Lara Bieler, Tobias Moser, Waltraud Kleindienst, Walter Wallner-Essl, Peter Koelblinger, Peter Wipfler, Andrea Harrer

Open access · goldAbstract readCase ReportsSystematic Review
In one paragraph

Synthesis in European journal of neurology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
2.8field-weighted citation impact, top 8% of its field
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

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 10 citations in OpenAlex.

  1. Pooled it
  2. Pain spectrum in immune checkpoint inhibitor-related adverse events: evolution, characteristics and management challenges based on bibliometrics.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2026
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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

9 authors at 1 institution in 1 country.

Ferdinand OttoDepartment of Neurology, Christian-Doppler University Hospital, Paracelsus Medical University, Center for Cognitive Neuroscience, member of EpiCARE, Salzburg, Austria.ORCID 0000-0003-1568-089X
Michael SeiberlDepartment of Neurology, Christian-Doppler University Hospital, Paracelsus Medical University, Center for Cognitive Neuroscience, member of EpiCARE, Salzburg, Austria.
Lara BielerDepartment of Neurology, Christian-Doppler University Hospital, Paracelsus Medical University, Center for Cognitive Neuroscience, member of EpiCARE, Salzburg, Austria.
Tobias MoserDepartment of Neurology, Christian-Doppler University Hospital, Paracelsus Medical University, Center for Cognitive Neuroscience, member of EpiCARE, Salzburg, Austria.ORCID 0000-0002-5397-5595
Waltraud KleindienstDepartment of Neurology, Christian-Doppler University Hospital, Paracelsus Medical University, Center for Cognitive Neuroscience, member of EpiCARE, Salzburg, Austria.
Walter Wallner-EsslDepartment of Neuroradiology, Christian-Doppler University Hospital, Paracelsus Medical University, Salzburg, Austria.
Peter KoelblingerDepartment of Dermatology and Allergology, Paracelsus Medical University, Salzburg, Austria.
Peter WipflerDepartment of Neurology, Christian-Doppler University Hospital, Paracelsus Medical University, Center for Cognitive Neuroscience, member of EpiCARE, Salzburg, Austria.
Andrea HarrerDepartment of Neurology, Christian-Doppler University Hospital, Paracelsus Medical University, Center for Cognitive Neuroscience, member of EpiCARE, Salzburg, Austria.
Paracelsus Medical University · AT

Funding

PMU-FFF R-18/01/100-HAP
6 · The paper itself

Abstract

background and purposeThis study was undertaken to raise awareness of a role of B cells in immune checkpoint inhibitor (ICI)-associated neurological immune-related adverse events (nirAE).

methodsA systematic literature review was made, with case observations of a melanoma and a non-small cell lung cancer (NSCLC) patient who developed ICI-associated nirAE with cerebrospinal fluid (CSF) findings indicating B cell involvement.

resultsTwo patients receiving ipilimumab/nivolumab for melanoma and chemotherapy/pembrolizumab for NSCLC developed nirAE in the form of myocarditis/myositis/myasthenia gravis overlap syndrome (triple M) and cerebellitis plus longitudinal transverse myelitis (c-LETM), respectively. Intrathecal inflammation with chemokine C-X-C motif ligand (CXCL13) elevation was present in both patients; the triple M case had acetylcholine receptor antibodies, antititin reactivity, altered CD4/CD8 T cell ratio in blood, and depressed programmed death-1 (PD-1) expression on CSF T cells; the c-LETM case showed intrathecal antibody production and plasma cells. Both patients insufficiently responded to first-line treatment. The NSCLC case improved upon administration of B cell-depleting therapy with rituximab, whereas the melanoma patient died before escalation therapy was initiated. Literature research revealed one additional ICI-associated LETM case with intrathecal CXCL13 elevation, three cases with ICI-associated aquaporin-4 antibody neuromyelitis spectrum disorder, and evidence of B cell-mediated toxicity based on antibody-mediated immune pathologies in ICI-associated immune-related adverse events.

conclusionsThe case observations highlight the plethora of uncertainties in diagnosis and treatment of ICI-associated nirAE, exemplify the heterogeneity of immune mechanisms involved, and suggest a role of B cells, which may be underdiagnosed. Intrathecal CXCL13 may serve as a biomarker of B cell involvement in nirAE, supported by intrathecal immunoglobulin synthesis, presence of plasma cells, and/or recruitment of cognate immune cells.

Indexed as

B-LymphocytesChemokine CXCL13Immune Checkpoint InhibitorsAgedAntibodies, Monoclonal, HumanizedFemaleHumansIpilimumabLung NeoplasmsMelanomaMyelitis, TransverseNivolumabT-LymphocytesAntibodies, Monoclonal, HumanizedChemokine CXCL13CXCL13 protein, humanImmune Checkpoint InhibitorsIpilimumabNivolumabpembrolizumabcerebrospinal fluidchemokine CXCL13immune checkpoint inhibitorimmune‐related neurological adverse events

Identifiers

PMID38556899
PMCPMC11235827
OpenAlexW4393383819

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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 OpenQuestion graph.