March 3, 2026

Antibody response against HERV-K polymerase and envelope by patients with multiple sclerosis

Key Points

The study identifies a significant antibody response to HERV-K polymerase and envelope in multiple sclerosis patients, revealing possible implications for disease understanding.
Patients with multiple sclerosis showed notable levels of antibodies against both HERV-K polymerase and envelope, indicating immune involvement.

Structured PICO

Do patients with multiple sclerosis have a higher humoral immune response against HERV-K polymerase and envelope peptides compared to healthy controls?

Population

31 patients with multiple sclerosis (MS) and 54 healthy individuals with no history of autoimmune diseases (total n=85)

Intervention

Evaluation of anti-HERV-K (polymerase) and HERV-W (envelope) antibodies using indirect ELISA with synthesized peptides

Comparator

Healthy population with no history of autoimmune diseases

Outcome

Immunoreactivity (humoral response) for HERV-K polymerase and envelope, and HERV-W envelope peptidessurrogate

Patients with multiple sclerosis exhibit a significant humoral immune response against HERV-K polymerase and envelope peptides, which may serve as a diagnostic tool and help understand viral immunology in MS.

Abstract

INTRODUCTION Human Endogenous Retroviruses (HERVs) are viruses that have infected germ cells of our ancestors millions of years ago and compose 8% of human genome. The expression of HERVs is associated with neurological disorders such as multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). The humoral immune response against peptides from the envelope proteins, but not to polymerase, of HERV-K has been previously described. The aim of this study is to evaluate anti-HERV- K polymerase (pol) humoral response in patients with MS. METHODS GenBank platform were used to select peptides with similarity above 50%, comparing HERV sequences (K or W) with the protein Myelin Oligodendrocyte Glycoprotein (MOG). The synthesized peptides were used in the ELISA test for anti-HERV-K (pol - polymerase) and W (env - envelope) antibodies in serum of patients with MS (31) and healthy population (54) with no history of autoimmune diseases. RESULTS One peptide (pep) related to HERV-W env and 8 peptides of HERV-K env or pol were selected and synthesized. Validation of the indirect ELISA with sera from MS patients showed that there was immunoreactivity for all peptides compared to healthy population (p < 0.0001). HERV-K env peptide 5 (WSGNQTLETRD) and 7 (ECVANSAVIL) showed the highest values of sensitivity and specificity, as well as diagnostic accuracy with 95.16% and 96.77%, respectively. HERV-K pol peptides 6 (LGIPTYAM), 8 (VTHVPSFR) and 9 (STVKTFTYLD) have demonstrated high values of accuracy 82.26, 80.65 and 82.26, respectively. These cutoff values were used to calculate the ELISA index - EI. The MS samples had a higher EI compared to the healthy population for almost all peptides of HERV-K pol (p < 0.001). CONCLUSION The present work showed a humoral response related to HERV-K pol and env, as well as HERV-W env, by patients with MS. All diagnostic parameters are appreciable, which makes it possible to use this tool to better understand the mechanisms related to viral immunology in patients.

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