TY - JOUR
T1 - Low cytomegalovirus seroprevalence in early multiple sclerosis: a case for the ‘hygiene hypothesis’?
AU - Alari-Pahissa, E.
AU - Moreira, A.
AU - Zabalza, A.
AU - Alvarez-Lafuente, R.
AU - Munteis, E.
AU - Vera, A.
AU - Arroyo, R.
AU - Alvarez-Cermeño, J. C.
AU - Villar, L. M.
AU - López-Botet, M.
AU - Martínez-Rodríguez, J. E.
PY - 2018/7/1
Y1 - 2018/7/1
N2 - © 2018 EAN Background and purpose: Cytomegalovirus (CMV) infection has recently been associated with a lower multiple sclerosis (MS) susceptibility, although it remains controversial whether it has a protective role or is merely an epiphenomenon related to westernization and early-life viral infections. We aimed to evaluate whether CMV serostatus may differ in patients with early MS as compared with patients with non-early MS, analyzing the putative association of this virus with MS clinical course and humoral immune responses against other herpesviruses. Methods: Multicentric analysis was undertaken of 310 patients with MS (early MS, disease duration ≤5 years, n = 127) and controls (n = 155), evaluating specific humoral responses to CMV, Epstein–Barr virus and human herpesvirus-6, as well as T-cell and natural killer (NK)-cell immunophenotypes. Results: Cytomegalovirus seroprevalence in early MS was lower than in non-early MS or controls (P < 0.01), being independently associated with disease duration (odds ratio, 1.04; 95% confidence interval, 1.01–1.08, P < 0.05). CMV+ patients with MS displayed increased proportions of differentiated T-cells (CD27−CD28−, CD57+, LILRB1+) and NKG2C+ NK-cells, which were associated with a lower disability in early MS (P < 0.05). CMV+ patients with early MS had an age-related decline in serum anti-EBNA-1 antibodies (P < 0.01), but no CMV-related differences in anti-human herpesvirus-6 humoral responses. Conclusions: Low CMV seroprevalence was observed in patients with early MS. Modification of MS risk attributed to CMV might be related to the induction of differentiated T-cell and NK-cell subsets and/or modulation of Epstein–Barr virus-specific immune responses at early stages of the disease.
AB - © 2018 EAN Background and purpose: Cytomegalovirus (CMV) infection has recently been associated with a lower multiple sclerosis (MS) susceptibility, although it remains controversial whether it has a protective role or is merely an epiphenomenon related to westernization and early-life viral infections. We aimed to evaluate whether CMV serostatus may differ in patients with early MS as compared with patients with non-early MS, analyzing the putative association of this virus with MS clinical course and humoral immune responses against other herpesviruses. Methods: Multicentric analysis was undertaken of 310 patients with MS (early MS, disease duration ≤5 years, n = 127) and controls (n = 155), evaluating specific humoral responses to CMV, Epstein–Barr virus and human herpesvirus-6, as well as T-cell and natural killer (NK)-cell immunophenotypes. Results: Cytomegalovirus seroprevalence in early MS was lower than in non-early MS or controls (P < 0.01), being independently associated with disease duration (odds ratio, 1.04; 95% confidence interval, 1.01–1.08, P < 0.05). CMV+ patients with MS displayed increased proportions of differentiated T-cells (CD27−CD28−, CD57+, LILRB1+) and NKG2C+ NK-cells, which were associated with a lower disability in early MS (P < 0.05). CMV+ patients with early MS had an age-related decline in serum anti-EBNA-1 antibodies (P < 0.01), but no CMV-related differences in anti-human herpesvirus-6 humoral responses. Conclusions: Low CMV seroprevalence was observed in patients with early MS. Modification of MS risk attributed to CMV might be related to the induction of differentiated T-cell and NK-cell subsets and/or modulation of Epstein–Barr virus-specific immune responses at early stages of the disease.
KW - Epstein–Barr virus
KW - cytomegalovirus
KW - herpesvirus
KW - hygiene hypothesis
KW - immunosenescence
KW - multiple sclerosis
KW - natural killer cells
U2 - 10.1111/ene.13622
DO - 10.1111/ene.13622
M3 - Article
VL - 25
SP - 925
EP - 933
JO - European Journal of Neurology
JF - European Journal of Neurology
SN - 1351-5101
IS - 7
ER -