HERV-K Modulates the Immune Response in ALS Patients

Area of Science:

• Immunology
• Neuroscience
• Virology

Background:

• Human endogenous retrovirus (HERV)-K env-su glycoprotein is implicated in amyotrophic lateral sclerosis (ALS).
• Previous studies linked HERV-K env-su _19-37 antibody levels to ALS disease severity.

Purpose of the Study:

• To investigate the humoral and cell-mediated immune response to specific HERV-K peptides in ALS patients.
• To quantify HERV-K env glycoprotein expression and cytokine/chemokine profiles after peptide stimulation.

Main Methods:

• Quantified HERV-K env glycoprotein expression on peripheral blood mononuclear cells (PBMCs) in ALS patients and healthy controls (HCs).
• Stimulated PBMCs with HERV-K env _19-37 and HERV-K env _109-126 peptides and measured cytokine/chemokine production.
• Analyzed immune cell populations including B cells, NK cells, CD19/B cells, and CD8/T cells.

Main Results:

• HERV-K env glycoprotein expression was higher on B cells and NK cells in ALS patients compared to HCs.
• HERV-K env _109-126 peptide stimulation increased IL-6 in CD19/B cells.
• Both peptides induced significant IFN-γ production in CD19/B cells, increased MIP-1α, and decreased MCP-1.
• HERV-K env _19-37 peptide stimulated TNF-α production in CD8/T cells.

Conclusions:

• HERV-K can modulate the immune system in ALS patients.
• HERV-K activation generates mediators primarily involved in the proinflammatory response.
• These findings suggest a potential role for HERV-K in ALS pathogenesis.