Serological profiling of the EBV immune response in Chronic Fatigue Syndrome using a peptide microarray Madlen Loebel, Maren Eckey, Franziska Sotzny, Elisabeth Hahn, Sandra Bauer, Patricia Grabowski, Johannes Zerweck, Pavlo Holenya, Leif G. Hanitsch, Kirsten Wittke, Peter Borchmann, Jens-Ulrich Rüffer, Falk Hiepe, Klemens Ruprecht, Uta Behrends, Carola Meindl, Hans-Dieter Volk, Ulf Reimer, Carmen Scheibenbogen http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0179124 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.