Mechanisms of immune tolerance breakdown in paraneoplastic neurological syndromes.

Autor: Peter E; Inserm U1314/UMR CNRS5284, SynatAc Team, MeLis Institute, Lyon, France; French Reference Center on Paraneoplastic Neurological Syndromes, Hospices Civils de Lyon, Lyon, France; University of Lyon, Université Claude-Bernard Lyon 1, Lyon, France., Dumez P; Inserm U1314/UMR CNRS5284, SynatAc Team, MeLis Institute, Lyon, France; French Reference Center on Paraneoplastic Neurological Syndromes, Hospices Civils de Lyon, Lyon, France; University of Lyon, Université Claude-Bernard Lyon 1, Lyon, France., Honnorat J; Inserm U1314/UMR CNRS5284, SynatAc Team, MeLis Institute, Lyon, France; French Reference Center on Paraneoplastic Neurological Syndromes, Hospices Civils de Lyon, Lyon, France; University of Lyon, Université Claude-Bernard Lyon 1, Lyon, France., Desestret V; Inserm U1314/UMR CNRS5284, SynatAc Team, MeLis Institute, Lyon, France; French Reference Center on Paraneoplastic Neurological Syndromes, Hospices Civils de Lyon, Lyon, France; University of Lyon, Université Claude-Bernard Lyon 1, Lyon, France. Electronic address: virginie.desestret@chu-lyon.fr.
Jazyk: angličtina
Zdroj: Revue neurologique [Rev Neurol (Paris)] 2024 Nov; Vol. 180 (9), pp. 931-939. Date of Electronic Publication: 2024 Sep 19.
DOI: 10.1016/j.neurol.2024.08.002
Abstrakt: Paraneoplastic neurological syndromes (PNS) are rare autoimmune disorders triggered by the presence of a cancer. The autoimmunity is herein directed against proteins expressed both in the tumor and in the nervous system, namely the onconeural antigens, against which are directed specific autoantibodies, each of them characterizing a neurological syndrome. The mechanisms of the immune tolerance breakdown in PNS leading to the production of specific autoantibodies directed against the nervous system and leading to the immune attack begins to be explained. Each syndrome is associated with a specific histo-molecular subtype of tumor suggesting a link between the PNS genesis and oncogenesis. The expression of the onconeural antigen by these tumors is insufficient to explain the immune tolerance breakdown. In some PNS tumors, alterations of the antigen have been identified: mutations, gene copy number variation and overexpression of transcript and protein. But in others PNS, no such molecular alterations of the onconeural antigens have been demonstrated. In these cases, other mechanisms of neoantigen generation that may be involved remain to be deciphered. Cancer outcomes of PNS tumors are also characterized by the high frequency of lymph node metastasis at diagnosis. At the primary tumor site, the antitumor immune reaction seems to be particularly intense and characterized by a prominence of B-cell and Ig-secreting plasma cells that may generate the autoantibody secretion. The immune control mechanisms leading to such organization of the immune attack are not known to date. Renewed research efforts are thus needed to better understand the mechanism of immune tolerance breakdown in each PNS and determine potential targets to meet the therapeutic challenges posed by these rare disorders.
(Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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