Concentrations of immunoglobulin free light chains in cerebrospinal fluid predict increased level of brain atrophy in multiple sclerosis

• Published in: Immunologic research 2018-12, Vol.66 (6), p.761-767
• Main Authors: Nazarov, Vladimir, Makshakov, Gleb, Kalinin, Ivan, Lapin, Sergey, Surkova, Elena, Mikhailova, Liya, Gilburd, Boris, Skoromets, Alexander, Evdoshenko, Evgeniy
• Format: Article
• Language: English
• Subjects: Adult; Allergology; Atrophy; Atrophy - immunology; Biomarkers; Biomedical and Life Sciences; Biomedicine; Blood-Brain Barrier - immunology; Brain; Brain - immunology; Brain Diseases - immunology; Cerebrospinal fluid; Cerebrospinal Fluid - immunology; Chains; Correlation analysis; Cross-Sectional Studies; Data acquisition; Enzyme-linked immunosorbent assay; Epidemiology; Female; Females; Humans; Immunoglobulin kappa-Chains - immunology; Immunoglobulin lambda-Chains - immunology; Immunoglobulins; Immunology; Internal Medicine; Light chains; Lymphocytes B; Magnetic resonance imaging; Male; Males; Medicine/Public Health; Multiple sclerosis; Multiple Sclerosis - immunology; Neurodegeneration; Original Article; Patients; Population studies; Quotients; Statistical analysis; Statistical methods; Statistical significance; Subgroups; Substantia alba; Substantia grisea
• ISSN: 0257-277X; 1559-0755
• DOI: 10.1007/s12026-018-9058-8

Recent studies showed that B cells play a major role in the pathogenesis of neurodegeneration in multiple sclerosis (MS). In this study, we aimed to determine the possible link between immunoglobulin free light chains (FLC) and brain atrophy in patients with MS. Ninety-two patients (32 males and 60 females) with MS were included. Kappa and lambda FLC concentrations in serum and cerebrospinal fluid (CSF) samples of MS patients were measured using ELISA assay. FLC quotients (Q-k and Q-λ, respectively) were calculated. In a cross-sectional group ( n  = 92), the MRI data were acquired within 6 months from the date of the lumbar puncture. Twenty patients from this cohort performed a follow-up MRI after 1 year of observation. Brain volumes were calculated with SIENAX and the brain atrophy (percentage brain volume change (PBVC)) was assessed with SIENA. Spearman’s test was performed to assess correlations. We have shown statistically significant correlation of Expanded Disability Status Scale (EDSS) level with normalized brain volume (NBV, r  = − 0.2721, p  = 0.0062), white matter volume (WMV, r  = − 0.2425, p  = 0.015), and gray matter volume (GMV, r  = − 0.216, p  = 0.0309). Multiple Sclerosis Severity Score (MSSS) score correlated with NBV ( r  = − 0.2521, p  = 0.0352) and WMV ( r  = − 0.315, p  = 0.0079). Neither EDSS, nor MSSS scores correlated with the age of patients and relapse rate during the first year and 5 years. In our study, we found statistically significant correlations of k-FLC in the CSF with NBV ( r  = − 0.311, p  = 0.003) and with GMV ( r  = − 0.213, p  = 0.0423). Q-k correlated only with NBV ( r  = − 0.340, p  = 0.006) and Q-λ were negatively correlated with WMV ( r  = − 0.366, p  = 0.003). We did not find correlations of k-FLC in CSF, λ-FLC in CSF, Q-k, and Q-λ with duration of MS course, EDSS, MSSS, number of relapses during the first year, and during the first 5 years of disease. Additionally, we subdivided the study population in accordance with level of k-FLC CSF, Q-k, and Q-λ on the 25th and 75th percentile subgroups (25-k-FLC CSF /75-k-FLC CSF ; 25-λ-FLC CSF /75-λ-FLC CSF ; 25-Q-k/75-Q-k; 25-Q-λ/75-Q-λ). We found statistically significant difference of NBV and GMV between 25-k-FLC CSF and 75-k-FLC CSF subgroups ( p  = 0.0047, p  = 0.0297 respectively), NBV between 25-Q-k and 75-Q-k subgroups ( p  = 0.038), and NBV and WMV between 25-Q-λ and 75-Q-λ subgroups ( p  = 0.0446, p  = 0.0026 respectively). PBVC in the prospective group showed