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Elevated Epstein–Barr virus‐encoded nuclear antigen‐1 immune responses predict conversion to multiple sclerosis
Author(s) -
Lünemann Jan D.,
Tintoré Mar,
Messmer Brady,
Strowig Till,
Rovira Álex,
Perkal Héctor,
Caballero Estrella,
Münz Christian,
Montalban Xavier,
Comabella Manuel
Publication year - 2010
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.21886
Subject(s) - immune system , antigen , multiple sclerosis , immunology , hazard ratio , medicine , virus , epstein–barr virus , antibody , measles virus , confidence interval , measles , vaccination
Objective The aims of the study were to determine the immune responses to candidate viral triggers of multiple sclerosis (MS) in patients with clinically isolated syndromes (CISs), and to evaluate their potential value in predicting conversion to MS. Methods Immune responses to Epstein–Barr virus (EBV), human herpesvirus 6, cytomegalovirus (HCMV), and measles were determined in a cohort of 147 CIS patients with a mean follow‐up of 7 years and compared with 50 demographically matched controls. Results Compared with controls, CIS patients showed increased humoral ( p < 0.0001) and cellular ( p = 0.007) immune responses to the EBV‐encoded nuclear antigen‐1 (EBNA1), but not to other EBV‐derived proteins. Immunoglobulin G (IgG) responses to other virus antigens and frequencies of T cells specific for HCMV and influenza virus gene products were unchanged in CIS patients. EBNA1 was the only viral antigen with which immune responses correlated with number of T2 lesions ( p = 0.006) and number of Barkhof criteria (p=0.001) at baseline, and with number of T2 lesions ( p = 0.012 at both 1 and 5 years), presence of new T2 lesions ( p = 0.003 and p = 0.028 at 1 and 5 years), and Expanded Disability Status Scale score ( p = 0.015 and p = 0.010 at 1 and 5 years) during follow‐up. In a univariate Cox regression model, increased EBNA1‐specific IgG responses predicted conversion to MS based on McDonald criteria (hazard ratio [95% confidence interval], 2.2 [1.2‐4.3]; p = 0.003). Interpretation Our results indicate that elevated immune responses toward EBNA1 are selectively increased in CIS patients and suggest that EBNA1‐specific IgG titers could be used as a prognostic marker for disease conversion and disability progression. ANN NEUROL 2010;67:159–169