Serological profiling of the EBV immune response in Chronic Fatigue Syndrome using a peptide microarray

Abstract

BACKGROUND: Epstein-Barr-Virus (EBV) plays an important role as trigger or cofactor for various autoimmune diseases. In a subset of patients with Chronic  Fatigue Syndrome (CFS) disease starts with infectious mononucleosis as late  primary EBV-infection, whereby altered levels of EBV-specific antibodies can be  observed in another subset of patients. METHODS: We performed a comprehensive  mapping of the IgG response against EBV comparing 50 healthy controls with 92 CFS  patients using a microarray platform. Patients with multiple sclerosis (MS),  systemic lupus erythematosus (SLE) and cancer-related fatigue served as controls.  3054 overlapping peptides were synthesised as 15-mers from 14 different EBV  proteins. Array data was validated by ELISA for selected peptides. Prevalence of  EBV serotypes was determined by qPCR from throat washing samples. RESULTS: EBV  type 1 infections were found in patients and controls. EBV seroarray profiles  between healthy controls and CFS were less divergent than that observed for MS or  SLE. We found significantly enhanced IgG responses to several EBNA-6 peptides  containing a repeat sequence in CFS patients compared to controls. EBNA-6 peptide  IgG responses correlated well with EBNA-6 protein responses. The EBNA-6 repeat  region showed sequence homologies to various human proteins. CONCLUSION: Patients  with CFS had a quite similar EBV IgG antibody response pattern as healthy  controls. Enhanced IgG reactivity against an EBNA-6 repeat sequence and against  EBNA-6 protein is found in CFS patients. Homologous sequences of various human  proteins with this EBNA-6 repeat sequence might be potential targets for  antigenic mimicry.