EBV-specific immune responses in patients with multiple sclerosis responding to IFNβ therapy.
BACKGROUND
Symptomatic primary infection with the human γ-herpesvirus Epstein-Barr virus (EBV) and elevated immune responses to EBV are associated with the development and progression of multiple sclerosis (MS). Interferon-beta (IFNβ), first-line treatment for relapse-onset MS, exhibits complex immunoregulatory and antiviral activities.


OBJECTIVE
To determine EBV-specific immune responses in patients with MS during IFNβ therapy.


METHODS
We evaluated cellular and humoral immune responses to EBV- and human cytomegalovirus (HCMV)-encoded antigens in patients with MS before and 1 year after IFNβ treatment by ELISA and flow cytometry. Twenty-eight patients with MS who showed a clinical response to IFNβ as defined by the absence of relapses and lack of progression on the Expanded Disability Status Scale score during the first 2 years of treatment were included.


RESULTS
Clinically effective IFNβ-therapy was associated with a downregulation of proliferative T cell responses to the latent EBV nuclear antigen-1 (EBNA1). EBNA1-specific IgG responses as well as cellular and humoral immune responses to MHC class I restricted EBV antigens expressed during lytic replication and viral B cell transformation were similar before and after IFNβ therapy. Although HCMV-specific IgG levels slightly decreased, proliferative T-cell responses towards HCMV antigens remained unchanged during IFNβ therapy.


CONCLUSIONS
Clinically effective IFNβ therapy is associated with a reduction of proliferative T-cell responses to EBNA1.
Centre d'Esclerosi Múltiple de Catalunya, CEM-Cat, Unitat de Neuroimmunologia Clínica, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
Manuel
M
Comabella
Kristina
K
Kakalacheva
Jordi
J
Río
Christian
C
Münz
Xavier
X
Montalban
Jan D
JD
Lünemann
D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D049109:Cell Proliferation / Q000187:drug effects; D003587:Cytomegalovirus / Q000276:immunology; D004185:Disability Evaluation; D004797:Enzyme-Linked Immunosorbent Assay; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D056724:Immunity, Humoral / Q000187:drug effects*; D007074:Immunoglobulin G / Q000097:blood; D007155:Immunologic Factors / Q000627:therapeutic use*; D016899:Interferon-beta / Q000627:therapeutic use*; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome
D000914:Antibodies, Viral; D019309:Epstein-Barr Virus Nuclear Antigens; D007074:Immunoglobulin G; D007155:Immunologic Factors; D016899:Interferon-beta; C417029:EBV-encoded nuclear antigen 1