دورية أكاديمية
أعرض في EDS

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.

التفاصيل البيبلوغرافية
العنوان: 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.
المؤلفون: Otto F; Department of Neurology, Christian-Doppler University Hospital, Paracelsus Medical University, Center for Cognitive Neuroscience, member of EpiCARE, Salzburg, Austria., Seiberl M; Department of Neurology, Christian-Doppler University Hospital, Paracelsus Medical University, Center for Cognitive Neuroscience, member of EpiCARE, Salzburg, Austria., Bieler L; Department of Neurology, Christian-Doppler University Hospital, Paracelsus Medical University, Center for Cognitive Neuroscience, member of EpiCARE, Salzburg, Austria., Moser T; Department of Neurology, Christian-Doppler University Hospital, Paracelsus Medical University, Center for Cognitive Neuroscience, member of EpiCARE, Salzburg, Austria., Kleindienst W; Department of Neurology, Christian-Doppler University Hospital, Paracelsus Medical University, Center for Cognitive Neuroscience, member of EpiCARE, Salzburg, Austria., Wallner-Essl W; Department of Neuroradiology, Christian-Doppler University Hospital, Paracelsus Medical University, Salzburg, Austria., Koelblinger P; Department of Dermatology and Allergology, Paracelsus Medical University, Salzburg, Austria., Wipfler P; Department of Neurology, Christian-Doppler University Hospital, Paracelsus Medical University, Center for Cognitive Neuroscience, member of EpiCARE, Salzburg, Austria., Harrer A; Department of Neurology, Christian-Doppler University Hospital, Paracelsus Medical University, Center for Cognitive Neuroscience, member of EpiCARE, Salzburg, Austria.; Department of Dermatology and Allergology, Paracelsus Medical University, Salzburg, Austria.
المصدر: European journal of neurology [Eur J Neurol] 2024 Jul; Vol. 31 (7), pp. e16279. Date of Electronic Publication: 2024 Mar 31.
نوع المنشور: Journal Article; Case Reports; Systematic Review
اللغة: English
بيانات الدورية: Publisher: Wiley Country of Publication: England NLM ID: 9506311 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1468-1331 (Electronic) Linking ISSN: 13515101 NLM ISO Abbreviation: Eur J Neurol Subsets: MEDLINE
أسماء مطبوعة: Publication: <2014- > : Oxford : Wiley
Original Publication: Oxford ; New York : Rapid Communications, [1994-
مواضيع طبية MeSH: B-Lymphocytes*/drug effects , B-Lymphocytes*/immunology , Chemokine CXCL13*/cerebrospinal fluid , Immune Checkpoint Inhibitors*/adverse effects, Aged ; Female ; Humans ; Antibodies, Monoclonal, Humanized/adverse effects ; Antibodies, Monoclonal, Humanized/administration & dosage ; Ipilimumab/adverse effects ; Ipilimumab/administration & dosage ; Lung Neoplasms/drug therapy ; Lung Neoplasms/immunology ; Melanoma/drug therapy ; Myelitis, Transverse/chemically induced ; Myelitis, Transverse/immunology ; Nivolumab/adverse effects ; Nivolumab/administration & dosage ; T-Lymphocytes/immunology ; T-Lymphocytes/drug effects
مستخلص: Background and Purpose: This study was undertaken to raise awareness of a role of B cells in immune checkpoint inhibitor (ICI)-associated neurological immune-related adverse events (nirAE).
Methods: A 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.
Results: Two 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.
Conclusions: The 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.
(© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)
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معلومات مُعتمدة: R-18/01/100-HAP PMU-FFF
فهرسة مساهمة: Keywords: cerebrospinal fluid; chemokine CXCL13; immune checkpoint inhibitor; immune‐related neurological adverse events
المشرفين على المادة: 0 (Antibodies, Monoclonal, Humanized)
0 (Chemokine CXCL13)
0 (CXCL13 protein, human)
0 (Immune Checkpoint Inhibitors)
0 (Ipilimumab)
31YO63LBSN (Nivolumab)
DPT0O3T46P (pembrolizumab)
تواريخ الأحداث: Date Created: 20240401 Date Completed: 20240607 Latest Revision: 20240727
رمز التحديث: 20240727
مُعرف محوري في PubMed: PMC11235827
DOI: 10.1111/ene.16279
PMID: 38556899
قاعدة البيانات: MEDLINE
الوصف
تدمد:1468-1331
DOI:10.1111/ene.16279