Diagnosic and Pronostic Values of Kappa and Lambda Free Light Chains in Central Nervous System Inflammatory Diseases

Study Overview
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Brief Summary
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Numerous studies have shown the diagnostic interest of cerebrospinal fluid kappa free light chains and kappa index in multiple sclerosis. However, large cohort studies are lacking and little is known about the correlation between kappa and lambda indexes and multiple sclerosis evidence disease activity. Therefore, this study plan to validate the kappa and lambda free light chains and indexes as diagnostic biomarker in multiple sclerosis and to correlate the concentration of kappa and lambda free light chains with clinical and radiological activity in a large cohort of patients.

Official Title
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Diagnosic and Pronostic Values of Kappa and Lambda Free Light Chains in Central Nervous System Inflammatory Diseases

Conditions
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Multiple Sclerosis, Central Nervous System Diseases

Intervention / Treatment
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* Other: Biological collection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients presenting with symptoms evocative of CNS involvement for who serum and cerebrospinal fluid kappa free light chains and kappa index are available Exclusion Criteria: Infectious CNS disease Tumor CNS disease Active CNS bleeding Monoclonal gammapathy Severe chronic renal failure (glomerular filtration rate <30 ml/mn)
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Mutliple sclerosis<br> | Other: Biological collection<br>* Collection of cerebrospinal fluid kappa and lambda free light chains and indexes<br>|
| CIS/RIS<br> | Other: Biological collection<br>* Collection of cerebrospinal fluid kappa and lambda free light chains and indexes<br>|
| Other CNS inflammatory diseases<br> | Other: Biological collection<br>* Collection of cerebrospinal fluid kappa and lambda free light chains and indexes<br>|
| Non inflammatory CNS diseases<br> | Other: Biological collection<br>* Collection of cerebrospinal fluid kappa and lambda free light chains and indexes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of cerebrospinal fluid (CSF) and serum kappa and lambda free light chains (KFLC and LFLC) | Measurement of cerebrospinal fluid (CSF) and serum KFLC and LFLC by a turbilimetric analyzer (data in mg/L) Quantification of QKFLC and QLFLC (CSF FLC/serum FLC) in each group of patients Compare median of QKFLC and QLFLC between groups | 1 day | 
| Measurement of cerebrospinal fluid (CSF) and serum albumin | Measurement of cerebrospinal fluid (CSF) and serum albumin by the same turbilimetric analyzer (data in mg/L) Quantification of albumin quotient (AQ) (CSF albumin/serum albumin) in each group of patients | 1 day | 
| Evaluation of the diagnostic performances of KFLC and LFLC intrathecal synthesis biomarkers (K/L FLC index and K/L FLC intrathecal fraction (IF)) for multiple sclerosis | Calculation of KFLC intrathecal synthesis biomarkers: KFLC index = (CSF KFLC/serum KFLC) / AQ KFLC IF = (KFLC(loc)/CSF KFLC) x 100 with: KFLC(loc) = ((CSF KFLC/serum KFLC) / Qk(lim)) x serum KFLC and Qk(lim) = 3.27 x (AQ^2 + 33)^0.5 - 8.2 Calculation of LFLC intrathecal synthesis biomarkers: LFLC index = (CSF LFLC/serum LFLC) / AQ) LFLC IF = (LFLC(loc)/CSF LFLC) x 100 with: LFLC(loc) = ((CSF LFLC/serum LFLC) / Ql(lim)) x serum LFLC and Ql(lim) = 2.1138 x AQ^0.865 Determination of diagnostic performances by ROC curve analysis and best cut-off values with the Younden index to calculate sensitivity, specificity and predictive values for MS diagnosis | 1 day | 
| Comparison of diagnostic performances of K/L FLC intrathecal synthesis biomarkers to oligoclonal bands (OCB) for multiple sclerosis | Identification of OCB status for each patient Calculation of diagnostic performances of OCB (sensitivity, specificity and predictive values) for MS diagnostic Comparison of diagnostic performances (sensitivity, specificity and predictive values) of OCB and K/L FLC intrathecal synthesis biomarkers for multiple sclerosis | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of clinical data that can alter KFLC and LFLC values | Identification of data that can be independtly associated with high or low CSF KFLC or LFLC values as potential bias in K/L FLC intrathecal synthesis biomarkers interpretation: Gender Age Type of clinical demyelinating event (i.e. myelitis, optic neuritis...) Immune modifying drug treatment ongoing during sampling Underlying disease activity (measured by the presence of subacute clinical symptoms ongoing at sampling or gadolinium enhanced lesions within the last MRI status) | 1 day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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multiple sclerosis, kappa free light chains, lambda free light chains