Antibody screening identifies HERV-K-related immune responses as candidate biomarkers in Parkinson's disease

Parkinson's disease (PD) is increasingly recognized as a disorder involving both neurodegenerative and immune-related mechanisms. To explore potential immune alterations associated with PD, we analyzed plasma antibody responses against a panel of viral and host synthetic linear epitopes in PD patients (n = 50) and healthy controls (HCs) (n = 54). Antibody levels against Interferon Regulatory Factor 5 (IRF5), Cathepsin B (CTSB), L-asparaginase (ASRGL1), Human Endogenous Retrovirus type K (HERV-K), Interferon-α (IFN-α), Interferon- ω (IFN-ω), α-synuclein, Herpes Simplex Virus type 1 (HSV-1), olfactory receptor proteins (OLF-R), and Dickkopf-related protein 3 (DKK3) were measured. PD patients showed significantly higher antibody levels against IRF5, CTSB, ASRGL1, and HSV-1 compared with controls, while antibodies against HERV-K were significantly lower. No differences were observed for IFN-α, IFN-ω, α-synuclein, OLF-R, or DKK3. Correlation analysis revealed several associations among antibody responses. IRF5 antibodies correlated positively with CTSB, ASRGL1, HERV-K, IFN-α, IFN-ω, and HSV-1. CTSB correlated with IFN-α, IFN-ω, HSV-1, OLF-R, and DKK3, while ASRGL1 correlated with HERV-K and IFN-ω. IFN-α correlated with IFN-ω, HSV-1, and DKK3, and IFN-ω correlated with HSV-1 and DKK3. HSV-1 antibodies were also associated with OLF-R and DKK3. Notably, HERV-K antibodies showed a negative correlation with DKK3. Stratification analyses indicated that antibody levels against HERV-K were higher in patients with milder disease stages accordingly with Hoehn and Yahr scale (HY 1-4) compared with HY 5, whereas IFN-α antibodies were increased in HY5 patients. Female patients generally showed lower antibody levels than males for different targets. No differences were observed according to disease duration. Overall, these findings indicate that PD patients display selective changes in antibody responses involving antiviral and host proteins. These targets may represent potential biomarkers of immune alterations in PD, although further studies are required to clarify the underlying biological mechanisms.