Scholarlink

<p>Autoimmune encephalitis (AE) is an inflammatory syndrome of the central nervous system (CNS) triggered by aberrant immune responses against neuronal intracellular (IC-AE) or surface (NS-AE) autoantigens. The resulting neuronal alterations and clinical trajectories differ, with IC-AE often leading to fatal outcomes. Unfortunately, the scarce availability of tissue from AE cases has hampered systematic analyses that would allow an understanding of the pathogenesis underlying neuronal alterations in T cell-mediated AE syndromes. Here, we assembled a cohort comprising both NS-AE (n = 8) and IC-AE (n = 12) from multiple institutions to delineate key histopathological features that distinguish neuronal pathology between IC-AE and NS-AE. In contrast to NS-AE, IC-AE lesions present a prominent neuronal pSTAT1 signature, accompanied by a high proportion of brain-resident memory CD8 + T cells and neurodegenerative GPNMB + phagocytes which show synaptic engulfment with little C3-complement deposition. Our findings highlight distinct histopathological features of IC-AE compared to NS-AE, providing actionable biomarkers for diagnostics and treatment strategies.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Neuronal pSTAT1 hallmarks synaptic pathology in autoimmune encephalitis against intracellular antigens

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年4月25日

查看全文
  • Giovanni Di Liberto,
  • Kristof Egervari,
  • Alberto Vogrig,
  • Marianna Spatola,
  • Margot Piccinno,
  • Ilena Vincenti,
  • Ingrid Wagner,
  • Mario Kreutzfeldt,
  • Verena Endmayr,
  • Karoline Ostertag,
  • Jasmin Rahimi,
  • Alex Vicino,
  • Anne-Katrin Pröbstel,
  • David Meyronet,
  • Stephan Frank,
  • Marco Prinz,
  • Ekkehard Hewer,
  • Jean-Philippe Brouland,
  • Laurence de Leval,
  • Laura Parkkinen,
  • Bogdan Draganski,
  • Virginie Desestret,
  • Divyanshu Dubey,
  • Sean J. Pittock,
  • Shanu F. Roemer,
  • Dennis W. Dickson,
  • Romana Höftberger,
  • Sarosh R. Irani,
  • Jérôme Honnorat,
  • Renaud Du Pasquier,
  • Doron Merkler

摘要

Autoimmune encephalitis (AE) is an inflammatory syndrome of the central nervous system (CNS) triggered by aberrant immune responses against neuronal intracellular (IC-AE) or surface (NS-AE) autoantigens. The resulting neuronal alterations and clinical trajectories differ, with IC-AE often leading to fatal outcomes. Unfortunately, the scarce availability of tissue from AE cases has hampered systematic analyses that would allow an understanding of the pathogenesis underlying neuronal alterations in T cell-mediated AE syndromes. Here, we assembled a cohort comprising both NS-AE (n = 8) and IC-AE (n = 12) from multiple institutions to delineate key histopathological features that distinguish neuronal pathology between IC-AE and NS-AE. In contrast to NS-AE, IC-AE lesions present a prominent neuronal pSTAT1 signature, accompanied by a high proportion of brain-resident memory CD8 + T cells and neurodegenerative GPNMB + phagocytes which show synaptic engulfment with little C3-complement deposition. Our findings highlight distinct histopathological features of IC-AE compared to NS-AE, providing actionable biomarkers for diagnostics and treatment strategies.