Contributions
Abstract: P859
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: The pathological significance and the diagnostic usefulness of intrathecal κ and λ free light chain (FLC) synthesis in Multiple Sclerosis (MS) are debated.
Methods: Paired cerebrospinal fluid (CSF) and serum specimens from 70 relapsing remitting MS (RRMS), 40 with and 30 without CSF restricted IgG Oligoclonal Band (IgGOB), and 37 from healthy controls (HC) were analyzed. IgG, IgM, κFLC and λFLC concentrations and indexes were evaluated. All RRMS performed MRI to estimate white and grey matter (WM) pathology.
Results: In HC, no intrathecal κ or λ FLC synthesis was found, and κFLC and λFLC Indexes were reciprocally correlated (r=0.67, p< 0.001). In RRMS, intrathecal κFLC or λFLC synthesis was demonstrated in respectively 66% and 43% of the cases, the Qκ/λ ratio was significantly higher compared to HC (17.0±31.3 vs 0.79±0.20, p< 0.001) and the correlation between κFLC Index and λFLC Index was weak (r:0.38, p< 0.05). Intrathecal IgG synthesis was associated with κFLC Index (IgG Index: r2=0.53, β=0.73, p< 0.001; IgGLOC: r2=0.37, β=0.61, p< 0.001; IgGIF: r2=0.69, β=0.83, p< 0.001), but not with λFLC Index, while intrathecal IgM synthesis correlated with λFLC Index (IgM Index: r=0.41, p< 0.001; IgMLOC: r=0.34, p< 0.005; IgMIF: r=0.45, p< 0.001), but not with κFLC Index. 26% of RRMS patients without IgGOB in the CSF had increased κFLC Index. Finally, no associations were observed between any CSF and MRI parameters.
Conclusions: The demonstration of intrathecal κFLC synthesis may further improve the diagnostic usefulness of CSF examination in RRMS. The marked increased in Qκ/λ further suggests a deregulated B-cell activation in MS pathology.
Disclosure: Miante Silvia reports travel grants from Novartis, Genzyme Sanofi, Biogen Italia, Almirall, Teva, Merck Serono, outside the submitted work.
Puthenparampil Marco received travel grant from Novartis, Almirall, Genzyme, Biogen Idec, Teva and Sanofi Aventis; he has been consultant for Genzyme and Biogen Idec.
De Zanet Andrea has nothing to disclose.
Altinier Sara has nothing to disclose.
Stropparo Erica has nothing to disclose.
Zywicki Sofia has nothing to disclose.
Poggiali Davide has nothing to disclose.
Cazzola Chiara has nothing to disclose.
Toffanin Elisabetta has nothing to disclose.
Ruggero Susanna has nothing to disclose.
Grassivaro Francesca has nothing to disclose.
Zaninotto Martina has nothing to disclose.
Plebani Mario has nothing to disclose.
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: P859
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: The pathological significance and the diagnostic usefulness of intrathecal κ and λ free light chain (FLC) synthesis in Multiple Sclerosis (MS) are debated.
Methods: Paired cerebrospinal fluid (CSF) and serum specimens from 70 relapsing remitting MS (RRMS), 40 with and 30 without CSF restricted IgG Oligoclonal Band (IgGOB), and 37 from healthy controls (HC) were analyzed. IgG, IgM, κFLC and λFLC concentrations and indexes were evaluated. All RRMS performed MRI to estimate white and grey matter (WM) pathology.
Results: In HC, no intrathecal κ or λ FLC synthesis was found, and κFLC and λFLC Indexes were reciprocally correlated (r=0.67, p< 0.001). In RRMS, intrathecal κFLC or λFLC synthesis was demonstrated in respectively 66% and 43% of the cases, the Qκ/λ ratio was significantly higher compared to HC (17.0±31.3 vs 0.79±0.20, p< 0.001) and the correlation between κFLC Index and λFLC Index was weak (r:0.38, p< 0.05). Intrathecal IgG synthesis was associated with κFLC Index (IgG Index: r2=0.53, β=0.73, p< 0.001; IgGLOC: r2=0.37, β=0.61, p< 0.001; IgGIF: r2=0.69, β=0.83, p< 0.001), but not with λFLC Index, while intrathecal IgM synthesis correlated with λFLC Index (IgM Index: r=0.41, p< 0.001; IgMLOC: r=0.34, p< 0.005; IgMIF: r=0.45, p< 0.001), but not with κFLC Index. 26% of RRMS patients without IgGOB in the CSF had increased κFLC Index. Finally, no associations were observed between any CSF and MRI parameters.
Conclusions: The demonstration of intrathecal κFLC synthesis may further improve the diagnostic usefulness of CSF examination in RRMS. The marked increased in Qκ/λ further suggests a deregulated B-cell activation in MS pathology.
Disclosure: Miante Silvia reports travel grants from Novartis, Genzyme Sanofi, Biogen Italia, Almirall, Teva, Merck Serono, outside the submitted work.
Puthenparampil Marco received travel grant from Novartis, Almirall, Genzyme, Biogen Idec, Teva and Sanofi Aventis; he has been consultant for Genzyme and Biogen Idec.
De Zanet Andrea has nothing to disclose.
Altinier Sara has nothing to disclose.
Stropparo Erica has nothing to disclose.
Zywicki Sofia has nothing to disclose.
Poggiali Davide has nothing to disclose.
Cazzola Chiara has nothing to disclose.
Toffanin Elisabetta has nothing to disclose.
Ruggero Susanna has nothing to disclose.
Grassivaro Francesca has nothing to disclose.
Zaninotto Martina has nothing to disclose.
Plebani Mario has nothing to disclose.
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.