Contributions
Abstract: P442
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Immunology
Background: Development of personalized health care for multiple sclerosis (MS) is hindered by a poor understanding of the biological processes underlying the disease, their interactions, and the heterogeneity between patients. Further progresses in the development of MS disease modifying treatments (DMT) largely depend on a greater knowledge of the immunological asset. Analysis of circulating immune cells by flow cytometry has revealed MS-associated alterations in the composition and function of T and B cell subsets, including temporal changes associated with disease activity and response to treatment.
Aim: By combining integrative omics, imaging and clinical data, we aim at developing algorithms that can be used in clinical practice to define the prognosis and select the best therapeutic approach.
Methods: We present cytomics data obtained in four European centers by flow cytometry of immune cell subsets in PBMC samples from 246 MS patients (age 42.5 ± 10 years; sex: 67.5% female; disease duration: 10.6 ± 8 years; subtype: 73.5% RRMS; 20% PMS; 6.5% CIS; mean EDSS: 2.4 ± 1.7) and 77 healthy controls (HC). Assays were strictly standardized using specifically prepared antibody-cocktail lyotubes. Differences between groups were assessed by analysis of covariance (ANCOVA) adjusting for sex and age.
Results: Comparison with HC indicated that the global MS population had significantly lower frequencies of naïve-Treg (p=0.007) and Th1/17 (p=0.04) and higher total Treg (p=0.004) and Breg (p=0.02). No differences in the same cell populations were found when focusing on untreated MS patients versus HC. Regarding the use of DMT, we found that patients receiving high-efficacy drugs had less naïve-Treg compared with the other groups separately (HC, untreated patients and patients receiving low efficacy drugs; p< 0.0001) and more total Treg and Breg compared to untreated patients (Treg p=0.02; Breg p=0.01) and HC (Treg p=0.0002; Breg p=0.007); such difference did not reach the statistical significance comparing patients receiving high-efficacy to those receiving low-efficacy drugs.
Conclusion: Our results show significant differences in specific immune cells populations between patients and controls. An increase in Treg and Breg frequencies was evident in treated patients, in particular in those receiving high-efficacy drugs. Such cytomics markers will be used in the development of clinical decision support systems for improving disease management.
Disclosure: This work was supported by the European Commission, ERACOSYSMED program (Sys4MS project). PV is currently an employe of Genentech. All other co-authors have not disclosures related with this study
Abstract: P442
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Immunology
Background: Development of personalized health care for multiple sclerosis (MS) is hindered by a poor understanding of the biological processes underlying the disease, their interactions, and the heterogeneity between patients. Further progresses in the development of MS disease modifying treatments (DMT) largely depend on a greater knowledge of the immunological asset. Analysis of circulating immune cells by flow cytometry has revealed MS-associated alterations in the composition and function of T and B cell subsets, including temporal changes associated with disease activity and response to treatment.
Aim: By combining integrative omics, imaging and clinical data, we aim at developing algorithms that can be used in clinical practice to define the prognosis and select the best therapeutic approach.
Methods: We present cytomics data obtained in four European centers by flow cytometry of immune cell subsets in PBMC samples from 246 MS patients (age 42.5 ± 10 years; sex: 67.5% female; disease duration: 10.6 ± 8 years; subtype: 73.5% RRMS; 20% PMS; 6.5% CIS; mean EDSS: 2.4 ± 1.7) and 77 healthy controls (HC). Assays were strictly standardized using specifically prepared antibody-cocktail lyotubes. Differences between groups were assessed by analysis of covariance (ANCOVA) adjusting for sex and age.
Results: Comparison with HC indicated that the global MS population had significantly lower frequencies of naïve-Treg (p=0.007) and Th1/17 (p=0.04) and higher total Treg (p=0.004) and Breg (p=0.02). No differences in the same cell populations were found when focusing on untreated MS patients versus HC. Regarding the use of DMT, we found that patients receiving high-efficacy drugs had less naïve-Treg compared with the other groups separately (HC, untreated patients and patients receiving low efficacy drugs; p< 0.0001) and more total Treg and Breg compared to untreated patients (Treg p=0.02; Breg p=0.01) and HC (Treg p=0.0002; Breg p=0.007); such difference did not reach the statistical significance comparing patients receiving high-efficacy to those receiving low-efficacy drugs.
Conclusion: Our results show significant differences in specific immune cells populations between patients and controls. An increase in Treg and Breg frequencies was evident in treated patients, in particular in those receiving high-efficacy drugs. Such cytomics markers will be used in the development of clinical decision support systems for improving disease management.
Disclosure: This work was supported by the European Commission, ERACOSYSMED program (Sys4MS project). PV is currently an employe of Genentech. All other co-authors have not disclosures related with this study