Comabella Manuel, Hegen Harald, Villar Luisa M, Rejdak Konrad, Sao-Avilés Augusto, Behrens Malina, Sastre-Garriga Jaume, Mongay Neus, Berek Klaus, Martínez-Yelamos Sergio, Pérez-Miralles Francisco, Abdelhak Ahmed, Bachhuber Franziska, Tumani Hayrettin, Lycke Jan, Carbonell-Mirabent Pere, Valls-Carbó Adrián, Rosenstein Igal, Alvarez-Lafuente Roberto, Castillo-Triviño Tamara, Otaegui David, Llufriu Sara, Blanco Yolanda, Sánchez-López Antonio J, García-Merino Antonio, Fissolo Nicolás, Gutiérrez Lucía, Villacieros-Álvarez Javier, Monreal Enric, Wiendl Heinz, Montalban Xavier, Lünemann Jan D
Servei de Neurologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED)-ISCIII, Madrid, Spain.
J Neurol. 2024 Dec 12;272(1):26. doi: 10.1007/s00415-024-12763-w.
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).
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.
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.
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.
病毒感染对疾病易感性和进展的影响主要在复发型多发性硬化症(RMS)患者中进行了研究。在此,我们确定了原发性进展型多发性硬化症(PPMS)患者对常见病毒的免疫反应。
在一个平均随访8年的68例PPMS患者队列中,测定了针对爱泼斯坦-巴尔病毒(EBV),特别是针对潜伏性EBV核抗原1和裂解性病毒衣壳抗原VCA、人类疱疹病毒6型(HHV-6)、人类巨细胞病毒(HCMV)和麻疹病毒的抗体反应,并与66名年龄和性别匹配的健康对照进行了比较。
与对照组相比,PPMS患者对EBV编码的核抗原-1(EBNA1)的体液免疫反应增强,但对裂解性EBV衣壳抗原(VCA)或其他病毒抗原的反应未增强。PPMS患者中HCMV的血清阳性率显著更高。基线时的抗病毒免疫反应与随时间的残疾进展无关。
原发性进展型疾病患者对EBNA1的免疫反应选择性升高,表明针对EBNA1的免疫反应与RMS和PPMS的发展之间存在联系。我们的数据还表明,慢性HCMV感染与进展型多发性硬化症有关。