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

PLoS One. 2017 Jun 12;12(6):e0179124. doi: 10.1371/journal.pone.0179124. eCollection 2017.

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.

MeSH terms

  • Adult
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • Antigens, Viral / immunology
  • Biomarkers
  • Cross Reactions
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes / immunology
  • Epstein-Barr Virus Infections / blood*
  • Epstein-Barr Virus Infections / complications
  • Epstein-Barr Virus Infections / immunology*
  • Epstein-Barr Virus Infections / virology
  • Fatigue Syndrome, Chronic / blood*
  • Fatigue Syndrome, Chronic / complications
  • Fatigue Syndrome, Chronic / epidemiology
  • Fatigue Syndrome, Chronic / immunology*
  • Female
  • Herpesvirus 4, Human / classification
  • Herpesvirus 4, Human / genetics
  • Herpesvirus 4, Human / immunology*
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Male
  • Middle Aged
  • Prevalence
  • Protein Array Analysis
  • Viral Load

Substances

  • Antibodies, Viral
  • Antigens, Viral
  • Biomarkers
  • Epitopes
  • Immunoglobulin G

Grant support

This work was supported by a grant 10158447 from the "Europäischen Fonds für regionale Entwicklung (EFRE)" of the European Union grant "Investition in Ihre Zukunft". The funder provided support in the form of salaries for authors PH, EM, UR, JZ and ML, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. The work was further supported by the Lost Voices Foundation e.V., and by a flex fund grant (07-905) from the German Center for Infection Research. The authors ME, JZ, PH and UR are employed by a commercial company, JPT Peptide Technologies GmbH, and received support in the form of salaries. JPT Peptide Technologies is not the funder of this study, but the recipient of the funding. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.