Fig. 1: EBNA-1_381-452-specific antibody titers are elevated in MS patients.

EBNA-1_381-452-specific IgG titers were quantified in N = 704 MS patients and N = 5381 controls by ELISA. A Bars represent the number of MS patients and controls with detectable (OD ≥ 0.32) EBNA-1_381-452-specific IgG antibody titers. Groups were compared using the two-sided Fisher’s exact test. B Violin plots represent the EBNA-1_381-452-specific IgG antibody titers of EBNA-1_381-452-specific IgG antibody seropositive MS patients (N = 689) and controls (N = 4189). Each data point represents one individual control or MS patient. Black lines indicate the median OD as well as the first and third quartiles. Dashed black lines indicate the cut-off for detection of EBNA-1_381-452-specific IgG antibody (OD ≥ 0.32). Groups were compared using the two-sided Mann-Whitney Test. C Forest plot for the discrimination of MS patients and controls based on the EBNA-1_381-452-specific IgG antibody titers. The number of MS patients (N = 704) and controls (N = 5381) with EBNA-1_381-452-specific IgG antibody titers above the indicated cut-offs were compared using Fisher’s exact test. The individual OR (±95% CI) for each cut-off is shown. D Two-sided ROC analysis (not correct for multiple comparisons) to discriminate between EBNA-1_381-452 IgG antibody seropositive MS patients (N = 689) and controls (N = 4189). E Distribution of MS patients and controls with high-level (OD ≥ 1.7), low level (OD ≤ 1.69 – ≥0.32), and absent (OD ≤ 0.31) EBNA-1_381-452-specific antibody titers. Groups were compared using the Chi-square test. F, G EBNA-1_381-452-specific IgG antibody titers are associated with axonal damage and MS disease severity. F Blots represent the number of MRI MS lesion in MS patients with high-level, low level, and absent EBNA-1_381-452-specific antibody titers. Groups were compared using the Chi-square test. G Plasma NfL concentrations were quantified in N = 704 MS patients at the time point of MS diagnosis by SIMOA. Blots represent the mean plasma NfL concentrations in MS patients with high-level, low level, and absent EBNA-1_381-452-specific antibody titers. Plasma NfL concentrations were compared between the groups using two-sided ANOVA and Dunn’s Post-Test. Source data are provided as a Source Data file. AUC: Area under the curve, EBNA-1: Epstein–Barr Virus Nuclear Antigen 1, MRI: Magnetic Resonance Imaging, MS: Multiple Sclerosis, NfL: Neurofilament Light Chain, OD: Optical Density. OR: Odds Ratio.