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

{"title":"Differences in innate immune cell populations distinguish autoimmune from herpesvirus-associated encephalitis","authors":"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","doi":"10.1016/j.jaut.2025.103396","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>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.</div><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"152 ","pages":"Article 103396"},"PeriodicalIF":7.9000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of autoimmunity","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0896841125000411","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}

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.

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

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.