CSF and blood signatures support classification of limbic encephalitis subtypes
Autoimmune limbic encephalitis (ALE) represents a heterogeneous disease associated with antibodies targeting extracellular (ALE<sub>extra</sub>) epitopes, intracellular (ALE<sub>intra</sub>) epitopes, anti-glutamic acid decarboxylase65 ALE (ALE<sub>GAD65</sub>), and ALE without detectable antibodies (ALE<sub>abneg</sub>). Combining analysis of cellular parameters, investigated by flow cytometry, and soluble parameters in the blood and cerebrospinal fluid (CSF) from a large cohort of 148 ALE patients (33 ALE<sub>extra</sub>, 12 ALE<sub>intra</sub>, 28 ALE-GAD65, 37 ALE<sub>abneg</sub>) in comparison to paradigmatic examples for neuro-inflammatory (51 relapsing remitting MS patients (RRMS)), and neuro-degenerative (34 Alzheimer's disease patients (AD)) diseases revealed discrete immune signatures in ALE subgroups. Identification of ALE-subtype specific markers facilitated classification of rare ALE-associated tumors, which may prompt further diagnostic efforts in clinical practice. While ALE<sub>intra</sub> exhibited features of neuro-inflammation, ALE<sub>extra</sub> displayed features of neuro-inflammation as well as neuro-degeneration. Moreover, ALE<sub>GAD65</sub> and ALE<sub>abneg</sub> lacked hallmarks of inflammation. This may explain the low efficacy of anti-inflammatory treatment regimens in ALE<sub>GAD65</sub> and presumably also ALE<sub>abneg</sub>.
Authors
- Niklas Meyer (ORCID: https://orcid.org/0000-0002-8377-097X)
- Judith Alferink (ORCID: https://orcid.org/0000-0002-3251-6584)
- Sven Guenther Meuth (ORCID: https://orcid.org/0000-0003-2571-3501)
- Heinz Wiendl (ORCID: https://orcid.org/0000-0003-4310-3432)
- Saskia Räuber (ORCID: https://orcid.org/0000-0001-8901-5572)
- Matthias Pawlowski (ORCID: https://orcid.org/0000-0001-6259-6100)
- Andreas Schulte‐Mecklenbeck (ORCID: https://orcid.org/0000-0003-3855-4706)
- Andre Dik (ORCID: https://orcid.org/0000-0003-4695-4136)
- Lisanne Korn (ORCID: https://orcid.org/0000-0002-4671-5701)
- Catharina C. Groß (ORCID: https://orcid.org/0000-0002-4872-9189)
- Stjepana Kovac (ORCID: https://orcid.org/0000-0002-2500-6893)
- Nico Melzer (ORCID: https://orcid.org/0000-0002-2420-701X)
- Christine Strippel (ORCID: https://orcid.org/0000-0002-7080-6769)
- Gerd Meyer zu Hörste (ORCID: https://orcid.org/0000-0002-4341-4719)
- Laura Bierhansl (ORCID: https://orcid.org/0000-0002-6752-690X)
- Harald Prüß
Institutions
- University of Münster (DE)
- University of Oxford (GB)
- University Hospital Münster (DE)
- Heinrich Heine University Düsseldorf (DE)
- Charité - Universitätsmedizin Berlin (DE)
Publication Details
- Journal
- Brain Behavior and Immunity
- Published
- 2024-10-12
- DOI
- https://doi.org/10.1016/j.bbi.2024.10.018
- Primary Topic
- Autoimmune Neurological Disorders and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Deutsche Forschungsgemeinschaft