Plasma proteome in LGI-1 autoimmune encephalitis.

Area of Science:

• Neuroimmunology
• Proteomics
• Transcriptomics

Background:

• Leucine-rich glioma-inactivated antibody associated autoimmune encephalitis (LGI-1 AE) is a rare autoimmune disorder affecting the central nervous system, leading to seizures and cognitive impairment.
• While immunotherapy can be effective, persistent cognitive deficits remain a challenge.
• Previous research indicated peripheral immune cell abnormalities in chronic LGI-1 AE.

Purpose of the Study:

• To investigate peripheral immune system alterations in acute and chronic LGI-1 AE.
• To identify potential biomarkers and therapeutic targets by analyzing plasma proteomic and monocyte transcriptomic profiles.

Main Methods:

• Plasma proteomic profiling using SomaLogic 11k panel on samples from acute LGI-1 AE, chronic LGI-1 AE, and healthy controls.
• Monocyte bulk RNA sequencing from chronic LGI-1 AE patients and controls.
• Differential expression analysis and pathway enrichment analysis (Gene Ontology Biological Processes).

Main Results:

• Plasma proteomic analysis revealed significant upregulation of innate immune activation, myeloid cell chemoattractants, complement cascade components, and lymphocyte signaling molecules in acute LGI-1 AE.
• Autophagy-related pathways were significantly downregulated in acute LGI-1 AE.
• Monocyte transcriptomics highlighted IL-6 signaling as a key dysregulated pathway, with 18 upregulated and 170 downregulated genes.

Conclusions:

• IL-6 signaling and terminal complement cascade activation are implicated in LGI-1 AE pathogenesis.
• Suppressed autophagy pathways represent a potential novel mechanism contributing to LGI-1 AE, warranting further investigation.
• These findings suggest opportunities for therapeutic repurposing and highlight the need for deeper understanding of autophagy's role in LGI-1 AE.