ArticleAnnals of neurology2022
Antibody Response to HML-2 May Be Protective in Amyotrophic Lateral Sclerosis.
Article in Annals of neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- Downregulation of miRNAs Accompanies Increased HERV-K (HML-2) Expression in Amyotrophic Lateral Sclerosis.Molecular neurobiology · 2026Article
- Antibody screening identifies HERV-K-related immune responses as candidate biomarkers in Parkinson's disease.Frontiers in cellular and infection microbiology · 2026Article
- Cutting-edge treatments in amyotrophic lateral sclerosis: the role of molecular pathogenesis in targeted therapies.Stem cell research & therapy · 2025Review
- Human Endogenous Retroviruses and Diseases.MedComm · 2025Review
- Machine learning predicts distinct biotypes of amyotrophic lateral sclerosis.European journal of human genetics : EJHG · 2025Article
- The prefusion structure of the HERV-K (HML-2) Env spike complex.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Human Endogenous Retroviruses as Novel Therapeutic Targets in Neurodegenerative Disorders.Vaccines · 2025Review
- A Characterization of the Humoral Immune Response to Human Endogenous Retroviruses andPathogens (Basel, Switzerland) · 2025Article
- Review
- The presence and clinical significance of autoantibodies in amyotrophic lateral sclerosis: a narrative review.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Review
- Review
- TDP-43 proteinopathy in ALS is triggered by loss of ASRGL1 and associated with HML-2 expression.Nature communications · 2024Article
- Activation of human endogenous retroviruses and its physiological consequences.Nature reviews. Molecular cell biology · 2024Review
- New Insights into Endogenous Retrovirus-K Transcripts in Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2024Article
- Antibody Response to HERV-K and HERV-W Envelope Epitopes in Patients with Myasthenia Gravis.International journal of molecular sciences · 2023Article
- Human Endogenous Retrovirus-K (HML-2)-Related Genetic Variation: Human Genome Diversity and Disease.Genes · 2023Review
- The Molecular Link Between TDP-43, Endogenous Retroviruses and Inflammatory Neurodegeneration in Amyotrophic Lateral Sclerosis: a Potential Target for Triumeq, an Antiretroviral Therapy.Molecular neurobiology · 2023Review
- Endogenous retroviruses and TDP-43 proteinopathy form a sustaining feedback driving intercellular spread of Drosophila neurodegeneration.Nature communications · 2023Article
- HERV-K Envelope Protein Induces Long-Lasting Production of Autoantibodies in T1DM Patients at Onset in Comparison to ZNT8 Autoantibodies.Pathogens (Basel, Switzerland) · 2022Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesReactivation of HERV-K(HML-2) has been found in subsets of individuals with amyotrophic lateral sclerosis (ALS). This study examines the antibody response against HML-2 in ALS and analyzes its clinical relevance.
methodsAntibodies to HML-2 envelope (env) were analyzed using a peptide array for epitope mapping and by a peptide enzyme-linked immunosorbent assay (ELISA) in 242 healthy donors, and 243 ALS and 85 multiple sclerosis (MS) individuals. Extracellular levels of HML-2 were analyzed by digital polymerase chain reaction (PCR).
resultsAntibodies in the sera of ALS individuals recognized more HML-2 env peptides compared to healthy controls (p < 0.0001). ALS individuals had higher levels of HML-2 than healthy donors (p = 0.02) and higher antibody levels against a select HML-2 env peptide compared to healthy donors or individuals with multiple sclerosis (p < 0.0001). 55.14% of ALS compared to 21.16% of healthy donors and 13.10% of MS individuals had antibodies against the HML-2 peptide (AUC = 0.769, p < 0.0001). Levels of extracellular HML-2 DNA in serum (p = 0.02) and the number of HML-2 env peptides recognized by ALS sera (p = 0.02) correlated with disease duration. Among ALS individuals, lower levels of HML-2 antibodies were associated with a definite diagnosis per EL Escorial criteria (p = 0.03), and with a lower predicted (p = 0.02) and observed survival (p = 0.03).
interpretationThere is a differential antibody response against specific epitopes of HML-2 env in ALS and controls, suggesting epitope spreading, likely due to persistent antigenic exposure following reactivation of the viral genes. Low levels of antibodies to HML-2 env in ALS are associated with poor prognosis and decreased survival probability. ANN NEUROL 2022;92:782-792.
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