Tdp‐43 and herv‐k envelope‐specific immunogenic epitopes are recognized in als patients

Abstract

The human endogenous retrovirus‐K (HERV‐K) and TAR DNA‐binding protein 43 (TDP‐ 43) have been associated with the pathophysiology of amyotrophic lateral sclerosis (ALS). Given these findings, we investigated the humoral response against HERV‐K envelope surface (env‐su) glycoprotein antigens and TDP‐43 in the plasma of ALS patients and healthy controls (HCs). The measured levels of Abs against the different epitopes’ fragments were significantly elevated in ALS patients, both in long‐survivor (LS) and newly diagnosed (ND) patients, compared to HCs. We observed a positive correlation between HERV‐K and TDP‐43 antibodies (Abs) levels, which seemed to strengthen with disease progression, that was not found in HCs. The TDP‐43 and HERV‐K epitopes identified in this study are highly immunogenic and recognized by the humoral response of ALS patients. Increased circulating levels of Abs directed against specific HERV‐K‐ and TDP‐43‐ derived epitopes could serve as possible biomarkers.