RT Journal Article
SR Electronic
T1 Increased cytomegalovirus immune responses at disease onset are protective in the long-term prognosis of patients with multiple sclerosis
JF Journal of Neurology, Neurosurgery & Psychiatry
JO J Neurol Neurosurg Psychiatry
FD BMJ Publishing Group Ltd
SP 173
OP 180
DO 10.1136/jnnp-2022-330205
VO 94
IS 3
A1 Comabella, Manuel
A1 Tintore, Mar
A1 Sao Avilés, Augusto
A1 Carbonell-Mirabent, Pere
A1 Malhotra, Sunny
A1 Rovira, Alex
A1 Fissolo, Nicolás
A1 Lünemann, Jan D
A1 Montalban, Xavier
YR 2023
UL http://jnnp.bmj.com/content/94/3/173.abstract
AB Objective It remains unclear whether viral infections interfere with multiple sclerosis (MS) disease progression. We evaluated the prognostic role of antibody responses toward viruses determined at disease onset on long-term disease outcomes.Methods Humoral immune responses against Epstein-Barr virus (EBV)-encoded nuclear antigen EBNA1, viral capsid antigen (VCA) and early antigen, and toward cytomegalovirus (HCMV), human herpesvirus 6 and measles were investigated in a cohort of 143 patients with MS for their association with long-term disability and inflammation disease outcomes.Results Median (IQR) follow-up was 20 (17.2–22.8) years. In univariable analysis, increased HCMV levels were associated with a lower risk to Expanded Disability Status Scale 4.0 (HR 0.95; 95% CI 0.91 to 0.99; p=0.03), to develop a secondary progressive MS (HR 0.94; 95% CI 0.90 to 0.99; p=0.02) and to first-line treatment (HR 0.98; 95% CI 0.96 to 0.99; p=0.04). High HCMV IgG levels were associated with a longer time to first-line treatment (p=0.01). Increased immune responses against EBV-VCA were associated with higher risk for first-line (HR 1.45; 95% CI 1.12 to 1.88; p=0.005) and second-line treatments (HR 2.03; 95% CI 1.18 to 3.49; p=0.01), and high VCA IgG levels were associated with shorter time to first-line (p=0.004) and second-line (p=0.02) therapies. EBNA1-specific IgG levels correlated with disease severity (0.17; p=0.04) and with an increased relapse rate during follow-up (relapse rate 1.26; 95% CI 1.03 to 1.56; p=0.02) that remained stable in multivariable analysis.Conclusions These results indicate that elevated immune responses against HCMV at disease onset have protective effects on long-term disability and inflammation disease outcomes. Our data also indicate that increased immune responses against EBV in early phases may influence long-term disease prognosis.Data are available on reasonable request.