Contributions
Abstract: EP1488
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 15 Immunology
Background: Multiple sclerosis (MS) is characterized by multiple immunological dysfunctions that lead to the expansion of T and B autoreactive clones and to intrathecal anti-central nervous system (CNS) antibody production. Although cerebrospinal fluid (CSF) B cells are easily accessible and may reflect relevant immune-pathological events within meninges and brain parenchyma, they have been poorly studied so far.
Aim: To characterize CSF B-cell subsets at clinical onset in order to evaluate their diagnostic and prognostic value.
Methods: Paired CSF and serum samples were obtained from 17 patients (13 RRMS, 4 CIS) and 20 individuals affected by not-inflammatory neurological diseases (NIND). The intrathecal IgG synthesis was evaluated by means of quantitative formulae and the demonstration of IgG oligoclonal bands (IgGOB). B cell subsets in the CSF were analyzed by Flow-Cytometry and classified in naive B cell (CD19+CD20+CD27-), memory B-cells (CD19+CD27+), plasmablasts (PB, CD19+CD27++CD38++CD138-) and plasmacells (PC, CD19+CD27++CD38++CD138+).
Results: Mild CSF pleocytosis (8.9cell/ul± 6.9) and detectable B-cells (2.0%± 0.5 of nucleated CD45+ cells) were found in RRMS patients but not in NIND (1.1cell/ul± 0.8) B cell (0.2±0.0). Memory B cell significantly varied among patients (60.7%±20.3 of CD19+), as well as PB (35.2 ± 15.1 of CD19+CD27+) and PC (64.1±14.7 of CD19+CD27+). Of note, no PB or PC could be detected in CIS patient. A mild correlation was observed between whole B cell and quantitative indexes of intrathecal IgG synthesis (r:0.6, p< 0.05 for both IgG Index and IgGIF). Further correlation analysis between quantitative indexes of intrathecal IgG synthesis and single B-cell subsets disclosed a strong correlation with PC (r: 0.89, p< 0.05 and r: 0.90, p< 0.05, respectively), and a correlation trend, even if not statistically significant, with PB (r: 0.80, p=0.055 and r: 0.68, p=0.137, respectively).
Conclusions: The correlation between CSF PC/PB and quantitative indexes of intrathecal IgG production supports an on-going follicular reaction. Whether this phenomenon is intrathecally-exclusive or occurs in the periphery as well, will need coupled analysis of CSF and blood samples investigations. Even though preliminary, the absence of PB and PC in CSF of CIS patients could suggest a role of these subsets in the conversion to clinically defined MS. Larger population and long-term follow-up will help to evaluate their diagnostic and prognostic values in MS.
Disclosure:
Grassivaro F, Venturini M, Toffanin E and Ruggero S have nothing to disclose.
Puthenparampil Marco received travel grant from Novartis, Sanofi-Genzyme, Biogen Idec, Almirall, Teva and Sanofi Aventis and honoraria from Almirall; he has been consultant for Genzyme
Federle Lisa has received funding for travel from Novartis, Merck Serono, Biogen Idec, Sanofi-Genzyme, Bayer Schering Pharma, Almirall, Teva and honoraria from MerkSerono, Teva and Almirall.
Rinaldi Francesca serves as an advisory board member of Biogen-Idec and has received funding for travel and speaker honoraria from Merck Serono, Biogen Idec, Sanofi-Aventis, Teva and Bayer Schering Pharma.
Perini Paola has received funding for travel and speaker honoraria from Merck Serono, Biogen Idec, Sanofi-Aventis, and Bayer Schering Pharma and has been consultant for Merck Serono, Biogen Idec and Teva;
Gallo Paolo has been a consultant for Bayer Schering, Biogen Idec, Genzyme, Merck Serono and Novartis; has received funding for travel and speaker honoraria from Merck-Serono, Biogen Idec, Sanofi-Aventis, Novartis Pharma and Bayer-Schering Pharma, Teva; has received research support from Bayer, Biogen Idec/Elan, MerkSerono, Genzyme and Teva; and has received research grant from the University of Padova, Veneto Region of Italy, the Italian Association for Multiple Sclerosis, the Italian Ministry of Public Health.
Abstract: EP1488
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 15 Immunology
Background: Multiple sclerosis (MS) is characterized by multiple immunological dysfunctions that lead to the expansion of T and B autoreactive clones and to intrathecal anti-central nervous system (CNS) antibody production. Although cerebrospinal fluid (CSF) B cells are easily accessible and may reflect relevant immune-pathological events within meninges and brain parenchyma, they have been poorly studied so far.
Aim: To characterize CSF B-cell subsets at clinical onset in order to evaluate their diagnostic and prognostic value.
Methods: Paired CSF and serum samples were obtained from 17 patients (13 RRMS, 4 CIS) and 20 individuals affected by not-inflammatory neurological diseases (NIND). The intrathecal IgG synthesis was evaluated by means of quantitative formulae and the demonstration of IgG oligoclonal bands (IgGOB). B cell subsets in the CSF were analyzed by Flow-Cytometry and classified in naive B cell (CD19+CD20+CD27-), memory B-cells (CD19+CD27+), plasmablasts (PB, CD19+CD27++CD38++CD138-) and plasmacells (PC, CD19+CD27++CD38++CD138+).
Results: Mild CSF pleocytosis (8.9cell/ul± 6.9) and detectable B-cells (2.0%± 0.5 of nucleated CD45+ cells) were found in RRMS patients but not in NIND (1.1cell/ul± 0.8) B cell (0.2±0.0). Memory B cell significantly varied among patients (60.7%±20.3 of CD19+), as well as PB (35.2 ± 15.1 of CD19+CD27+) and PC (64.1±14.7 of CD19+CD27+). Of note, no PB or PC could be detected in CIS patient. A mild correlation was observed between whole B cell and quantitative indexes of intrathecal IgG synthesis (r:0.6, p< 0.05 for both IgG Index and IgGIF). Further correlation analysis between quantitative indexes of intrathecal IgG synthesis and single B-cell subsets disclosed a strong correlation with PC (r: 0.89, p< 0.05 and r: 0.90, p< 0.05, respectively), and a correlation trend, even if not statistically significant, with PB (r: 0.80, p=0.055 and r: 0.68, p=0.137, respectively).
Conclusions: The correlation between CSF PC/PB and quantitative indexes of intrathecal IgG production supports an on-going follicular reaction. Whether this phenomenon is intrathecally-exclusive or occurs in the periphery as well, will need coupled analysis of CSF and blood samples investigations. Even though preliminary, the absence of PB and PC in CSF of CIS patients could suggest a role of these subsets in the conversion to clinically defined MS. Larger population and long-term follow-up will help to evaluate their diagnostic and prognostic values in MS.
Disclosure:
Grassivaro F, Venturini M, Toffanin E and Ruggero S have nothing to disclose.
Puthenparampil Marco received travel grant from Novartis, Sanofi-Genzyme, Biogen Idec, Almirall, Teva and Sanofi Aventis and honoraria from Almirall; he has been consultant for Genzyme
Federle Lisa has received funding for travel from Novartis, Merck Serono, Biogen Idec, Sanofi-Genzyme, Bayer Schering Pharma, Almirall, Teva and honoraria from MerkSerono, Teva and Almirall.
Rinaldi Francesca serves as an advisory board member of Biogen-Idec and has received funding for travel and speaker honoraria from Merck Serono, Biogen Idec, Sanofi-Aventis, Teva and Bayer Schering Pharma.
Perini Paola has received funding for travel and speaker honoraria from Merck Serono, Biogen Idec, Sanofi-Aventis, and Bayer Schering Pharma and has been consultant for Merck Serono, Biogen Idec and Teva;
Gallo Paolo has been a consultant for Bayer Schering, Biogen Idec, Genzyme, Merck Serono and Novartis; has received funding for travel and speaker honoraria from Merck-Serono, Biogen Idec, Sanofi-Aventis, Novartis Pharma and Bayer-Schering Pharma, Teva; has received research support from Bayer, Biogen Idec/Elan, MerkSerono, Genzyme and Teva; and has received research grant from the University of Padova, Veneto Region of Italy, the Italian Association for Multiple Sclerosis, the Italian Ministry of Public Health.