Abstract
Human endogenous retrovirus (HERV)-K env-su glycoprotein has been documented in amyotrophic lateral sclerosis (ALS), where HERV-K env-su 19–37 antibody levels significantly correlated with clinical measures of disease severity. Herein, we investigated further the humoral and cell-mediated immune response against specific antigenic peptides derived from HERV-K in ALS. HERV-K env glycoprotein expression on peripheral blood mononuclear cells (PBMCs) membrane and cytokines and chemokines after stimulation with HERV-K env 19–37 and HERV-K env 109–126 were quantified in patients and healthy controls (HCs). HERV-K env glycoprotein was more expressed in B cells and NK cells of ALS patients compared to HCs, whereas HERV-K env transcripts were similar in ALS and HCs. In ALS patients, specific stimulation with HERV-K env 109–126 peptide showed a higher expression of IL-6 by CD19/B cells. Both peptides, however, were able to induce a great production of IFN-γ by stimulation CD19/B cells, and yielded a higher expression of MIP-1α and a lower expression of MCP-1. HERV-K env 19–37 peptide induced a great production of TNF-α in CD8/T cells. In conclusion, we observed the ability of HERV-K to modulate the immune system, generating mediators mainly involved in proinflammatory response.
Highlights
Introduction published maps and institutional affilAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects both upper and lower motor neurons, determining progressive paralysis and death, within3–5 years post diagnosis
By using the intracellular cytokine (ICC) method, we evaluated in peripheral blood mononuclear cells (PBMCs), the immune response T and B mediated after stimulation with specific peptides
Regarding Human endogenous retrovirus (HERV)-K env-su 109–126 peptide, 76% of amyotrophic lateral sclerosis (ALS) patients and 16% of healthy controls (HCs) were positive for Abs in sera (AUC = 0.9, p < 0.0001) (Figure 1b)
Summary
Introduction published maps and institutional affilAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects both upper and lower motor neurons, determining progressive paralysis and death, within3–5 years post diagnosis. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects both upper and lower motor neurons, determining progressive paralysis and death, within. About 5–10% of ALS cases are familial, the remaining are apparently sporadic of unknown etiology [1]. A poor knowledge of ALS pathophysiology is the major reason for the absence of specific diagnostic tests in clinical practice and the lack of an effective treatment. It is important to find reliable diagnostic and prognostic markers that can guide the clinical diagnostic process at an early stage of the disease. There is no cure for ALS, and the FDA-approved drugs are only marginally effective in slowing the progression of the disease by a few months [1]. Several studies have demonstrated the presence of reverse transcriptase activity in serum samples of both ALS patients and their unaffected relatives [2,3], indicating that a common inherited iations
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