Objective Vitamin D deficiency and Epstein–Barr virus (EBV) infection may be associated with the development of multiple sclerosis (MS). We investigated serum 25-hydroxyvitamin D (25-OH-D) levels and anti-EBV immunoreactivity in 25 individuals before the first clinical manifestation of MS.
Patients and methods 56 serum samples of 25 individuals who had donated blood prior to the first clinical MS manifestation (clinically isolated syndrome (CIS)) (four male subjects, 21 female subjects, mean age 31.5 years at time of pre-CIS blood sampling; mean age at disease onset 33.4 years) were available, covering an interval of 7.3 years–2 months (mean 31.5 months) before CIS. In 18 of 25 patients serum samples were also obtained after established diagnosis of MS. Longitudinal age- and gender-matched healthy blood donors (four male subjects, 21 female subjects, 39 samples, mean age 32.5 years) served as controls. Serum 25-OH-D was measured by isotope dilution-liquid chromatography-tandem mass spectrometry. 25-OH-D levels were deconvoluted using published seasonal coefficients from a German population. Immunoglobulin G (IgG) against Epstein–Barr virus nuclear antigen-1 (EBNA1) were assessed using commercially available ELISA.
Results Low 25-OH-D levels were observed during the 24-month pre-CIS interval (47.8 (32.5–77.2) nmol/l, median (IQR); healthy controls: 81.6 (57.7–98.5), p=0.004, however, still higher than after established diagnosis (24.5 (13.7–47.7), p<0.0001 compared with controls). IgG against EBNA1 during the 36-month pre-CIS interval was increased (185.9 (91.2–460.0) IU/ml, median (IQR); healthy controls 63.7 (29.5–121.6), p=0.002).
Conclusions Low vitamin D and remote EBV infection may be associated with clinical MS breakthrough within 2–3 years.
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BFD and NvA contributed equally to this work.
Funding This work was supported by grants from the German Ministry for Education and Research (BMBF, ‘German Competence Network Multiple Sclerosis’ (KKNMS), grant number CONTROL MS, 01GI0914).
Competing interests BF Décard has received personal compensation for activities with Teva. N von Ahsen, T Grunwald, F Streit, P Niggemeier, V Schottstedt and J Riggert have no conflicts of interest. A Stroet has received personal compensation for activities with Novartis, Almirall Hermal GmbH and Sanofi. R Gold received personal compensation for activities with Bayer Healthcare, Biogen Idec and Teva Neuroscience and in an editorial capacity from Therapeutic Advances in Neurological Disorders. R Gold has received patent payments from Biogen Idec and research support from the German Ministry for Education and Research (BMBF, ‘German Competence Network Multiple Sclerosis’ (KKNMS), CONTROL MS, 01GI0914), Bayer Healthcare, Biogen Idec, Merck Serono, Novartis and Teva Neuroscience. A Chan received personal compensation as a speaker or consultant for Bayer Schering, Biogen Idec, Merck Serono, Novartis, Sanofi-Aventis and Teva Neuroscience. A Chan received research support from the German Ministry for Education and Research (BMBF, ‘German Competence Network Multiple Sclerosis’ (KKNMS), CONTROL MS, 01GI0914), Bayer Schering, Biogen Idec, Merck Serono and Novartis.
Patient consent Obtained.
Ethics approval The study was approved by the local ethics committee.
Provenance and peer review Not commissioned; externally peer reviewed.
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