Low vitamin D and elevated immunoreactivity against Epstein-Barr virus before first clinical manifestation of multiple sclerosis.
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.


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.
Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, Gudrunstr. 56, 44791 Bochum, Germany.
Bernhard F
BF
Décard
Nicolas
N
von Ahsen
Thomas
T
Grunwald
Frank
F
Streit
Anke
A
Stroet
Petra
P
Niggemeier
Volkmar
V
Schottstedt
Joachim
J
Riggert
Ralf
R
Gold
Andrew
A
Chan
D000328:Adult; D017668:Age of Onset; D001782:Blood Donors; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D005858:Germany; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D006887:Hydroxycholecalciferols / Q000097:blood; D007074:Immunoglobulin G / Q000032:analysis; D008297:Male; D009103:Multiple Sclerosis / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D053719:Tandem Mass Spectrometry; D014808:Vitamin D Deficiency / Q000097:blood / Q000150:complications / Q000175:diagnosis*
D006887:Hydroxycholecalciferols; D007074:Immunoglobulin G