Epstein-Barr virus-specific intrathecal oligoclonal IgG production in relapsing-remitting multiple sclerosis is limited to a subset of patients and is composed of low-affinity antibodies.
BACKGROUND
The purpose of this study was to investigate intrathecal production and affinity distributions of Epstein-Barr virus (EBV)-specific antibodies in multiple sclerosis (MS) and controls.


METHODS
Cerebrospinal fluid (CSF) and serum concentrations, quantitative intrathecal synthesis, oligoclonal bands (OCB) patterns and affinity distributions of anti-Epstein Barr virus (EBV) antibodies were evaluated in 100 relapsing-remitting MS (RRMS) patients and 200 age- and sex-matched controls with other inflammatory neurological disorders (OIND) and other noninflammatory neurological disorders (NIND).


RESULTS
Levels of anti-EBNA-1 and anti-viral capsid antigen (VCA) IgG were different in both the CSF (P <0.0001 and P <0.01, respectively) and serum (P <0.001 and P <0.05, respectively) among the RRMS, OIND and NIND. An intrathecal synthesis of anti-EBNA-1 IgG and anti-VCA IgG, as indicated by the antibody index, was underrepresented in the RRMS, OIND and NIND (range 1 to 7%). EBV-specific OCB were detected in 24% of the RRMS patients and absent in the controls. High-affinity antibodies were more elevated in the RRMS and in the OIND than in the NIND for CSF anti-EBNA-1 IgG (P <0.0001) and anti-VCA IgG (P <0.0001). After treatment with increasing concentrations of sodium thiocyanate, the EBV-specific IgG OCB had low affinity in all 24 RRMS patients analyzed.


CONCLUSIONS
Our findings do not support the potential role of an EBV persistent brain chronic infection in MS and suggest that an EBV-specific intrathecal oligoclonal IgG production can occur in a subset of MS patients as part of humoral polyreactivity driven by chronic brain inflammation.
Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, Via Aldo Moro 8, I-44124, Cona Ferrara, Italy. massimiliano.castellazzi@unife.it.
Massimiliano
M
Castellazzi
Department of Medical Sciences, University of Ferrara, Via Aldo Moro 8, I-44124, Cona Ferrara, Italy. carlo.contini@unife.it.
Carlo
C
Contini
Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, Via Aldo Moro 8, I-44124, Cona Ferrara, Italy. carmine.tamborino@unife.it.
Carmine
C
Tamborino
Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, Via Aldo Moro 8, I-44124, Cona Ferrara, Italy. ffasolo@sissa.it.
Francesca
F
Fasolo
Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, Via Aldo Moro 8, I-44124, Cona Ferrara, Italy. gloria.roversi1981@gmail.com.
Gloria
G
Roversi
Department of Medical Sciences, University of Ferrara, Via Aldo Moro 8, I-44124, Cona Ferrara, Italy. srcslv@unife.it.
Silva
S
Seraceni
Department of Medical Sciences, University of Ferrara, Via Aldo Moro 8, I-44124, Cona Ferrara, Italy. roberta.rizzo@unife.it.
Roberta
R
Rizzo
Department of Neurosciences and Rehabilitation, Azienda Ospedaliero-Universitaria, Via Aldo Moro 8, I-44124, Cona Ferrara, Italy. e.baldi@ospfe.it.
Eleonora
E
Baldi
Department of Neurosciences and Rehabilitation, Azienda Ospedaliero-Universitaria, Via Aldo Moro 8, I-44124, Cona Ferrara, Italy. mr.tola@ospfe.it.
Maria Rosaria
MR
Tola
Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, Via Aldo Moro 8, I-44124, Cona Ferrara, Italy. tiziana.bellini@unife.it.
Tiziana
T
Bellini
Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, Via Aldo Moro 8, I-44124, Cona Ferrara, Italy. enrico.granieri@unife.it.
Enrico
E
Granieri
Department of Neurosciences and Rehabilitation, Azienda Ospedaliero-Universitaria, Via Aldo Moro 8, I-44124, Cona Ferrara, Italy. e.fainardi@ospfe.it.
Enrico
E
Fainardi
D000328:Adult; D000914:Antibodies, Viral / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D005260:Female; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D043025:Oligoclonal Bands / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*
D000914:Antibodies, Viral; D015415:Biomarkers; D007074:Immunoglobulin G; D043025:Oligoclonal Bands