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

Abstract

BackgroundEpstein-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.MethodsWe 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.ResultsEBV 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.ConclusionPatients 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.

Chronic viral infections in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

“…In addition, these serum antibodies could persist for several years, indicating that immune disturbances may allow viral reactivation [ 71 ]. An abnormal immune response to EBV infection has been reported in ME/CFS cases; however, later publication showed no differences of EBV prevalence among patients and controls [ 72 , 73 ]. Although Manian and colleagues found higher titers of IgG class antibodies against EBV viral capsid antigen in patients than in controls, they did not find a statistically significant difference in titers of antibodies to early antigens of EBV, HSV-1, HSV-2 and HHV-6 in patients compared to healthy controls.…”

“…In contrast, reduced CMV and HSV specific B-cell responses were not identified. On the other hand, the presence of antibodies against EBV DNA polymerase and EBV-encoded dUTPase has been detected in the serum of a subset of ME/CFS patients but not in controls [ 84 ], and the IgG response to EBV EBNA-6 peptides has been heightened in ME/CFS [ 73 ]. Sequences of amino acids in the EBNA-6 repeat region were found to be homologous to the human lactoperoxidase precursor (LPO) and thyroid peroxidase precursor (TPO) proteins as well as the two enzymes ornithine transcarbamylase (OTC) and phosphofructokinase-1 (PFK-1), which have metabolic functions.…”

Principles of the treatment of chronic Epstein–Barr virus infection and associated diseases

“…В основе патогенеза данного синдрома лежит тяжелая гипервоспалительная реакция иммунных клеток, в первую очередь тканевых макрофагов, моноцитов и лимфоцитов. Заболевание развивается у детей чаще, чем у взрослых, вероятность летального исхода составляет 40 усталости, в патогенезе которого большую роль также играют герпесвирусы человека 6-го и 7-го типов [14]. Клинические проявления включают физическую усталость и когнитивную дисфункцию, значительно снижающие работоспособность и регистрирующиеся в течение 6 мес в отсутствие других причин.…”

Influence of the Epstein-Barr Virus Persistence upon the Development of the ImmuneMediated Somatic Diseases

“…Ранее у пациентов с синдромом хронической усталости был описан повышенный уровень IgM к капсидному антигену вируса Эпштейна-Барр, ряду ранних антигенов вируса, в то время как уровень IgG обычно был сопоставим с таковым у латентно инфицированных Эпштейна-Барр вирусом людей без этого синдрома. При недавнем тщательном изучении иммунного ответа на белки вируса обнаружено повышение уровеня IgG к латентному антигену EBNA-6 (альтернативное название EBNA-3С), характерное для группы людей с синдромом хронической усталости [28]. Имеет значение, что эта группа людей инфицирована именно 1-м типом вируса Эпштейна-Барр, который отличается от 2-го типа как раз структурой гена, кодирующего EBNA-3 (A, B, C).…”