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. 2024 Dec 12;272(1):26.
doi: 10.1007/s00415-024-12763-w.

Increased EBNA1-specific antibody response in primary-progressive multiple sclerosis

Manuel Comabella  1   2 , Harald Hegen  3 , Luisa M Villar  4 , Konrad Rejdak  5 , Augusto Sao-Avilés  1 , Malina Behrens  6 , Jaume Sastre-Garriga  1 , Neus Mongay  1 , Klaus Berek  3 , Sergio Martínez-Yelamos  7 , Francisco Pérez-Miralles  8 , Ahmed Abdelhak  9   10 , Franziska Bachhuber  9 , Hayrettin Tumani  9 , Jan Lycke  11 , Pere Carbonell-Mirabent  1 , Adrián Valls-Carbó  11 , Igal Rosenstein  12 , Roberto Alvarez-Lafuente  13 , Tamara Castillo-Triviño  2   14 , David Otaegui  2   15 , Sara Llufriu  16 , Yolanda Blanco  16 , Antonio J Sánchez-López  17   18 , Antonio García-Merino  17 , Nicolás Fissolo  1   2 , Lucía Gutiérrez  1 , Javier Villacieros-Álvarez  1 , Enric Monreal  19 , Heinz Wiendl  6 , Xavier Montalban  1 , Jan D Lünemann  20
Affiliations

Increased EBNA1-specific antibody response in primary-progressive multiple sclerosis

Manuel Comabella et al. J Neurol. .

Abstract

Background and objectives: The impact of viral infections on disease susceptibility and progression has predominantly been studied in patients with relapse-onset MS (RMS). Here, we determined immune responses to ubiquitous viruses in patients with primary progressive MS (PPMS).

Methods: Antibody responses to Epstein-Barr virus (EBV), specifically to the latent EBV nuclear antigen 1 and the lytic viral capsid antigen VCA, human herpesvirus 6 (HHV-6), human cytomegalovirus (HCMV), and measles virus were determined in a cohort of 68 PPMS patients with a mean follow-up of 8 years and compared with 66 healthy controls matched for sex and age.

Results: Compared with controls, PPMS patients showed increased humoral immune responses to the EBV-encoded nuclear antigen-1 (EBNA1), but not to the lytic EBV capsid antigen (VCA) or to other viral antigens. Seroprevalence rates for HCMV were significantly higher in PPMS. Antiviral immune responses at baseline did not correlate with disability progression over time.

Discussion: Elevated immune responses toward EBNA1 are selectively increased in people with primary progressive disease, indicating a link between EBNA1-targeting immune responses and the development of both RMS and PPMS. Our data also suggest that chronic HCMV infection is associated with progressive MS.

Keywords: Epstein–Barr virus; Human cytomegalovirus; Multiple sclerosis; Primary progressive; Virus.

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Conflict of interest statement

Declarations. Conflicts of interest: The authors declare that they have no competing interests to declare that are relevant to the content of this article.

Figures

Fig. 1
Fig. 1
Selective increase of EBNA1-specific IgG response in PPMS patients graphs show the distribution of IgG immune responses against ubiquitous viruses in patients with PPMS compared to healthy donors (HD) matched by sex and age. The non-parametric Mann–Whitney U test was used to compare antibody responses between the 2 groups. EBV Epstein–Barr virus, EBNA1 Epstein–Barr nuclear antigen 1, HCMV human cytomegalovirus, HHV-6 human herpesvirus 6, VCA viral capsid antigen
See this image and copyright information in PMC

References

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