M Puthenparampil1, S Altinier2, E Stropparo3, S Zywicki4, D Poggiali5, C Cazzola4, E Toffanin6, S Ruggero7, F Grassivaro8, M Zaninotto9, M Plebani10, P Gallo11. 1. Multiple Sclerosis Centre, Department of Neuroscience DNS, Università degli Studi di Padova, Via Giustiniani 5, 35128, Padova. Electronic address: marco.puthenparampil@studenti.unipd.it. 2. Department of Laboratory Medicine, Università degli Studi di Padova, Via Giustiniani 2, 35128, Padova. Electronic address: sara.altinier@aopd.veneto.it. 3. Multiple Sclerosis Centre, Department of Neuroscience DNS, Università degli Studi di Padova, Via Giustiniani 5, 35128, Padova. Electronic address: ericastropparo@yahoo.it. 4. Multiple Sclerosis Centre, Department of Neuroscience DNS, Università degli Studi di Padova, Via Giustiniani 5, 35128, Padova. 5. Department of Mathematics, Università degli Studi di Padova, Via Trieste 63, 35121, Padova. Electronic address: poggiali@math.unipd.it. 6. Multiple Sclerosis Centre, Department of Neuroscience DNS, Università degli Studi di Padova, Via Giustiniani 5, 35128, Padova. Electronic address: elisabetta.toffanin@unipd.it. 7. Multiple Sclerosis Centre, Department of Neuroscience DNS, Università degli Studi di Padova, Via Giustiniani 5, 35128, Padova. Electronic address: susanna.ruggero@unipd.it. 8. Multiple Sclerosis Centre, Department of Neuroscience DNS, Università degli Studi di Padova, Via Giustiniani 5, 35128, Padova. Electronic address: Francesca.grassivaro@unipd.it. 9. Department of Laboratory Medicine, Università degli Studi di Padova, Via Giustiniani 2, 35128, Padova. Electronic address: martina.zaninotto@aopd.veneto.it. 10. Department of Laboratory Medicine, Università degli Studi di Padova, Via Giustiniani 2, 35128, Padova. Electronic address: mario.plebano@unipd.it. 11. Multiple Sclerosis Centre, Department of Neuroscience DNS, Università degli Studi di Padova, Via Giustiniani 5, 35128, Padova. Electronic address: paolo.gallo@unipd.it.
Abstract
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 CSF-restricted IgGOB had increased κFLCLOC. 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.
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 CSF-restricted IgGOB had increased κFLCLOC. 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.
Authors: Franz Felix Konen; Philipp Schwenkenbecher; Konstantin Fritz Jendretzky; Stefan Gingele; Kurt-Wolfram Sühs; Hayrettin Tumani; Marie Süße; Thomas Skripuletz Journal: Cells Date: 2021-11-06 Impact factor: 6.600