Differences in innate immune cell populations distinguish autoimmune from herpesvirus-associated encephalitis

IF 7.9 1区医学 Q1 IMMUNOLOGY

Journal of autoimmunity Pub Date : 2025-03-01 DOI:10.1016/j.jaut.2025.103396

Saskia Räuber , Andreas Schulte-Mecklenbeck , Kelvin Sarink , Kristin S. Golombeck , Christina B. Schroeter , Alice Willison , Christopher Nelke , Christine Strippel , Andre Dik , Marco Gallus , Stjepana Kovac , Heinz Wiendl , Gerd Meyer zu Hörste , Tobias Ruck , Oliver M. Grauer , Udo Dannlowski , Tim Hahn , Catharina C. Gross , Sven G. Meuth , Nico Melzer

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引用次数: 0

Abstract

Background

Autoimmune encephalitis (AIE) is a disabling inflammatory condition of the brain deemed to be due to a dysregulated immune response. Viral infections and malignancies together with certain genetic polymorphisms are thought to contribute to the pathogenesis of AIE, yet the exact mechanisms remain insufficiently understood. Diagnosis of AIE currently relies on clinical consensus criteria. However, diagnostic workup can be challenging in some cases, potentially delaying treatment initiation associated with poor clinical outcomes.

This study aims to investigate the systemic and intrathecal immune cell profiles of AIE in comparison to viral meningoencephalitis (VME) as a clinically relevant differential diagnosis and evaluate its diagnostic and therapeutic potential.

Methods

97 mainly treatment-naïve AIE patients, 47 patients with VME, and 109 somatic symptom disorder (SD) controls were included. Analysis of peripheral blood (PB) and cerebrospinal fluid (CSF) immune cell profiles was performed using multidimensional flow cytometry (mFC) in combination with novel computational approaches.

Results

We were able to identify alterations in the adaptive B and T cell-mediated immune response in AIE compared to SD controls which correspond to respective changes in the brain parenchyma. AIE and VME exhibit similar patterns of adaptive B and T cell responses and differ in pattern of innate immunity especially NK cells. MFC together with routine CSF parameters can differentiate AIE from VME and SD controls implying diagnostic potential.

Conclusion

AIE is characterized by a B and T cell-mediated systemic and intrathecal immune-cell signature which corresponds to changes reported in the brain parenchyma providing insights into immunopathogenesis. Differences between AIE and VME were most prominent for the innate immune response indicating a potential role of NK cells in the pathogenesis of autoimmunity. Our data provides evidence that mFC could be a novel complementary approach to the diagnosis of AIE with diagnostic, therapeutic, and prognostic implications.

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先天免疫细胞群的差异区分了自身免疫性脑炎和疱疹病毒相关脑炎

自身免疫性脑炎（AIE）是一种大脑致残性炎症，被认为是由于免疫反应失调所致。病毒感染和恶性肿瘤以及某些遗传多态性被认为与AIE的发病机制有关，但其确切机制尚不清楚。AIE的诊断目前依赖于临床共识标准。然而，在某些情况下，诊断检查可能具有挑战性，可能会延迟与临床结果不佳相关的治疗开始。本研究旨在探讨AIE与病毒性脑膜脑炎（VME）的全身和鞘内免疫细胞谱，作为临床相关的鉴别诊断，并评估其诊断和治疗潜力。方法97例主要为treatment-naïve AIE患者，47例VME患者，109例躯体症状障碍（SD）对照。使用多维流式细胞术（mFC）结合新的计算方法分析外周血（PB）和脑脊液（CSF）免疫细胞谱。结果与SD对照组相比，我们能够识别AIE中适应性B细胞和T细胞介导的免疫反应的改变，这对应于脑实质的各自变化。AIE和VME表现出相似的适应性B细胞和T细胞应答模式，但在先天免疫特别是NK细胞应答模式上存在差异。MFC和常规CSF参数可以区分AIE与VME和SD控制，这意味着诊断潜力。结论aie的特点是B和T细胞介导的全身和鞘内免疫细胞特征，这与脑实质的变化相对应，为免疫发病机制提供了新的认识。AIE和VME之间的差异在先天免疫反应中最为突出，表明NK细胞在自身免疫发病机制中的潜在作用。我们的数据提供了证据，证明mFC可能是AIE诊断的一种新的补充方法，具有诊断、治疗和预后意义。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of autoimmunity 医学-免疫学

CiteScore

27.90

自引率

1.60%

发文量

117

审稿时长

17 days

期刊介绍： The Journal of Autoimmunity serves as the primary publication for research on various facets of autoimmunity. These include topics such as the mechanism of self-recognition, regulation of autoimmune responses, experimental autoimmune diseases, diagnostic tests for autoantibodies, as well as the epidemiology, pathophysiology, and treatment of autoimmune diseases. While the journal covers a wide range of subjects, it emphasizes papers exploring the genetic, molecular biology, and cellular aspects of the field. The Journal of Translational Autoimmunity, on the other hand, is a subsidiary journal of the Journal of Autoimmunity. It focuses specifically on translating scientific discoveries in autoimmunity into clinical applications and practical solutions. By highlighting research that bridges the gap between basic science and clinical practice, the Journal of Translational Autoimmunity aims to advance the understanding and treatment of autoimmune diseases.