Contributions
Abstract: P1082
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Immunology
Introduction: B-cells have an important role in Multiple Sclerosis (MS). Epstein-Barr virus (EBV), a γ-herpesvirus which could be implicated in MS pathogenesis, establishes a chronic infection in B cells. Human cytomegalovirus (HCMV) is a β-herpesvirus related to lower MS susceptibility that induces an adaptive reconfiguration of the NK-cell compartment which has been associated with a decreased risk of progression. However, the influence of EBV and HCMV in the B-cell compartment of healthy controls (HC) and MS patients is not well established.
Objective: To evaluate the immunophenotype of peripheral B-cells in MS and HC according to clinical characteristics and herpesviruses serostatus (EBV and HCMV).
Methods: Seventy-three MS patients (55 Relapsing-remitting MS (RRMS), 18 progressive forms (PMS)) and 40 HC were included in the study. 28 MS patients were treated with disease-modifying therapies (DMT) (23 interferon-β, 5 glatiramer acetate). Herpesviruses serostatus was obtained by standard diagnostic tests. All samples were analysed by flow cytometry evaluating B-cell subsets according to surface expression of CD19, CD38, CD10, CD27, IgD and IgM.
Results: EBV seroprevalence was higher in MS patients as compared to HC (98.6% vs. 85%, p< 0.01), contrasting with similar HCMV seroprevalence (MS 63%, HC 70%, p=0.54). MS patients and HC had no differences in the proportions of plasmablasts, naïve, memory unswitched and switched B-cells. The proportions of transitional B-cells (CD38+CD10+) were higher in DMT-treated as compared to untreated patients (6.2%±4.8 vs. 3.2%±2.1; p< 0.01). Considering herpervirus seroprevalence, no differences were found in B-cell subsets in relation to EBV serostatus. By contrast, a DMT-related increase in transitional B-cells was found in RRMS HCMV+ but not in HCMV- patients (7.8%±5.6 vs. 4.0%±1.4; p< 0.01). In HCMV- cases, a greater proportion of naïve B-cells (CD38-CD10-IgD+CD27-) was observed in PMS as compared to RRMS and HC (60.8%±10.3, 47.2%±18.0, 42.7%±11.2, respectively; p< 0.05), without differences according to MS form in HCMV+ cases. EDSS inversely correlated with unswitched B-cells (CD38-CD10-IgD+CD27+) in HCMV+ (p< 0.01), but not in HCMV- patients.
Conclusion: HCMV seropositivity appears associated to changes in the distribution of peripheral B-cell subsets in MS, related to DMT. Further studies are required to confirm these findings and evaluate whether the response to DMT may be influenced by this herpesvirus infection.
Disclosure: Supported by a grant from Biogen Idec via the IMIM (Hospital del Mar Medical Research Institute) and FIS/PI17/00254 (Spanish Ministry of Economy and Competitiveness).
Ana Zabalza has received travel funding from Biogen Idec and Novartis, personal fees for a lecture from Eisai and a study grant from Novartis.
Antia Moreira has received travel funding from Teva and Biogen Idec, personal fees for a lecture from Genzyme and a study grant from Novartis.
Elvira Munteis has received personal fees for consulting services and lectures from Merck-Serono, Biogen Idec, Teva, Genzyme, Novartis, Bayer and Almirall.
Jose E.Martínez-Rodríguez has participated as principal investigator in pharmaceutical company-sponsored clinical trials including Novartis, Roche, Merck-Serono, Actelion, and Celgene, and personal fees for consulting services and lectures from Roche, Novartis, Biogen Idec and Merck-Serono.
Elisenda Alari-Pahissa: nothing to disclose
Andrea Vera: nothing to disclose
Miguel López-Botet: nothing to disclose
Abstract: P1082
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Immunology
Introduction: B-cells have an important role in Multiple Sclerosis (MS). Epstein-Barr virus (EBV), a γ-herpesvirus which could be implicated in MS pathogenesis, establishes a chronic infection in B cells. Human cytomegalovirus (HCMV) is a β-herpesvirus related to lower MS susceptibility that induces an adaptive reconfiguration of the NK-cell compartment which has been associated with a decreased risk of progression. However, the influence of EBV and HCMV in the B-cell compartment of healthy controls (HC) and MS patients is not well established.
Objective: To evaluate the immunophenotype of peripheral B-cells in MS and HC according to clinical characteristics and herpesviruses serostatus (EBV and HCMV).
Methods: Seventy-three MS patients (55 Relapsing-remitting MS (RRMS), 18 progressive forms (PMS)) and 40 HC were included in the study. 28 MS patients were treated with disease-modifying therapies (DMT) (23 interferon-β, 5 glatiramer acetate). Herpesviruses serostatus was obtained by standard diagnostic tests. All samples were analysed by flow cytometry evaluating B-cell subsets according to surface expression of CD19, CD38, CD10, CD27, IgD and IgM.
Results: EBV seroprevalence was higher in MS patients as compared to HC (98.6% vs. 85%, p< 0.01), contrasting with similar HCMV seroprevalence (MS 63%, HC 70%, p=0.54). MS patients and HC had no differences in the proportions of plasmablasts, naïve, memory unswitched and switched B-cells. The proportions of transitional B-cells (CD38+CD10+) were higher in DMT-treated as compared to untreated patients (6.2%±4.8 vs. 3.2%±2.1; p< 0.01). Considering herpervirus seroprevalence, no differences were found in B-cell subsets in relation to EBV serostatus. By contrast, a DMT-related increase in transitional B-cells was found in RRMS HCMV+ but not in HCMV- patients (7.8%±5.6 vs. 4.0%±1.4; p< 0.01). In HCMV- cases, a greater proportion of naïve B-cells (CD38-CD10-IgD+CD27-) was observed in PMS as compared to RRMS and HC (60.8%±10.3, 47.2%±18.0, 42.7%±11.2, respectively; p< 0.05), without differences according to MS form in HCMV+ cases. EDSS inversely correlated with unswitched B-cells (CD38-CD10-IgD+CD27+) in HCMV+ (p< 0.01), but not in HCMV- patients.
Conclusion: HCMV seropositivity appears associated to changes in the distribution of peripheral B-cell subsets in MS, related to DMT. Further studies are required to confirm these findings and evaluate whether the response to DMT may be influenced by this herpesvirus infection.
Disclosure: Supported by a grant from Biogen Idec via the IMIM (Hospital del Mar Medical Research Institute) and FIS/PI17/00254 (Spanish Ministry of Economy and Competitiveness).
Ana Zabalza has received travel funding from Biogen Idec and Novartis, personal fees for a lecture from Eisai and a study grant from Novartis.
Antia Moreira has received travel funding from Teva and Biogen Idec, personal fees for a lecture from Genzyme and a study grant from Novartis.
Elvira Munteis has received personal fees for consulting services and lectures from Merck-Serono, Biogen Idec, Teva, Genzyme, Novartis, Bayer and Almirall.
Jose E.Martínez-Rodríguez has participated as principal investigator in pharmaceutical company-sponsored clinical trials including Novartis, Roche, Merck-Serono, Actelion, and Celgene, and personal fees for consulting services and lectures from Roche, Novartis, Biogen Idec and Merck-Serono.
Elisenda Alari-Pahissa: nothing to disclose
Andrea Vera: nothing to disclose
Miguel López-Botet: nothing to disclose