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

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.

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.

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).

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.