Contributions
Abstract: P596
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: Intrathecal synthesis of oligoclonal immunoglobulins (OCB) is the pathogenic hallmark of B-cell activation in multiple sclerosis. OCB positivity is a well-defined prognostic marker of higher rate of disability progression. Except for immunoglobulin production, B-cell activation is characterized by increased production of immunoglobulin free light chains kappa and lambda (k-FLC, λ-FLC). The influence of FLC on disease progression remains to be controversial.
Objectives: To define correlations of intrathecal concentrations of FLC with clinical measures of MS progression and the risk of reaching disability milestones.
Methods: We retrospectively analyzed 442 cases of multiple sclerosis, defined by the McDonald criteria 2005/2010, from our database. The mean duration of the disease was 10±7.4 years. The rate of clinical disability progression was measured by the Multiple Sclerosis Severity Score (MSSS), assessed at the date of the last follow-up. OCB were detected in cerebrospinal fluid (CSF) with isoelectric focusing electrophoresis. FLC concentrations in serum and CSF were measured using ELISA. Reference values were defined in our previous publications as >0.595 µg/ml for k-FLCCSF, >0.1 µg/ml for λ-FLCCSF and >0.0422 for Q-kappa. Correlations between MSSS and laboratory markers were counted using nonparametric Spearman"s r-value. Hazard ration for progression to EDSS 6.0 was defined for high and low k-FLCCSF, λ-FLCCSF, Q-kappa and positive and negative OCB with Kaplan-Meier survival analysis (log-rank).
Results: Positive correlations were detected between MSSS and k-FLCSERUM (r=0.1576, p=0.0205), k-FLCCSF (r=0.1326, p=0.0347). No significant correlations were found between MSSS and λ-FLCCSF, λ-FLCSERUM and Q-kappa. Survival analysis revealed an increased risk for long-term progression of disability (EDSS=6.0) for high k-FLCCSF (HR=2.109, p=0.0316) and OCB-positivity (HR=2.722, p=0.0411). Concentrations of λ-FLCCSF and Q-kappa showed no significant impact on disability progression.
Conclusions: k-FLC concentrations in serum and CSF showed significant correlations with MSSS. k-FLCCSF and OCB, but not λ-FLCCSF possess prognostic value for disability progression according to the survival analysis. Q-kappa wasn"t showed to be a prognostic biomarker, probably due to variations of FLC concentrations in the blood.
Disclosure: Gleb Makshakov reports no disclosures.
Vladimir Nazarov reports no disclosures.
Elena Surkova reports no disclosures.
Elena Shchegolkova reports no disclosures.
Ekaterina Kairbekova reports no disclosures.
Maria Shumilina reports no disclosures.
Sergey Lapin reports no disclosures.
Evgeniy Evdoshenko has received and dedicated to research support fees for board membership, consultancy or speaking, or grants, in the last 2 years from Biogen Idec, Sanofi-Aventis, Genzyme, Pharmstandart, R-Pharm, Pharmsyntez, Genfa Medica, Takeda, Generium, Johnson & Johnson, CIA, GlaxoSmithKline, Bayer, Teva, Merck, Actellion, Roche, Biocad
Abstract: P596
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: Intrathecal synthesis of oligoclonal immunoglobulins (OCB) is the pathogenic hallmark of B-cell activation in multiple sclerosis. OCB positivity is a well-defined prognostic marker of higher rate of disability progression. Except for immunoglobulin production, B-cell activation is characterized by increased production of immunoglobulin free light chains kappa and lambda (k-FLC, λ-FLC). The influence of FLC on disease progression remains to be controversial.
Objectives: To define correlations of intrathecal concentrations of FLC with clinical measures of MS progression and the risk of reaching disability milestones.
Methods: We retrospectively analyzed 442 cases of multiple sclerosis, defined by the McDonald criteria 2005/2010, from our database. The mean duration of the disease was 10±7.4 years. The rate of clinical disability progression was measured by the Multiple Sclerosis Severity Score (MSSS), assessed at the date of the last follow-up. OCB were detected in cerebrospinal fluid (CSF) with isoelectric focusing electrophoresis. FLC concentrations in serum and CSF were measured using ELISA. Reference values were defined in our previous publications as >0.595 µg/ml for k-FLCCSF, >0.1 µg/ml for λ-FLCCSF and >0.0422 for Q-kappa. Correlations between MSSS and laboratory markers were counted using nonparametric Spearman"s r-value. Hazard ration for progression to EDSS 6.0 was defined for high and low k-FLCCSF, λ-FLCCSF, Q-kappa and positive and negative OCB with Kaplan-Meier survival analysis (log-rank).
Results: Positive correlations were detected between MSSS and k-FLCSERUM (r=0.1576, p=0.0205), k-FLCCSF (r=0.1326, p=0.0347). No significant correlations were found between MSSS and λ-FLCCSF, λ-FLCSERUM and Q-kappa. Survival analysis revealed an increased risk for long-term progression of disability (EDSS=6.0) for high k-FLCCSF (HR=2.109, p=0.0316) and OCB-positivity (HR=2.722, p=0.0411). Concentrations of λ-FLCCSF and Q-kappa showed no significant impact on disability progression.
Conclusions: k-FLC concentrations in serum and CSF showed significant correlations with MSSS. k-FLCCSF and OCB, but not λ-FLCCSF possess prognostic value for disability progression according to the survival analysis. Q-kappa wasn"t showed to be a prognostic biomarker, probably due to variations of FLC concentrations in the blood.
Disclosure: Gleb Makshakov reports no disclosures.
Vladimir Nazarov reports no disclosures.
Elena Surkova reports no disclosures.
Elena Shchegolkova reports no disclosures.
Ekaterina Kairbekova reports no disclosures.
Maria Shumilina reports no disclosures.
Sergey Lapin reports no disclosures.
Evgeniy Evdoshenko has received and dedicated to research support fees for board membership, consultancy or speaking, or grants, in the last 2 years from Biogen Idec, Sanofi-Aventis, Genzyme, Pharmstandart, R-Pharm, Pharmsyntez, Genfa Medica, Takeda, Generium, Johnson & Johnson, CIA, GlaxoSmithKline, Bayer, Teva, Merck, Actellion, Roche, Biocad