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

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.

Study Overview

• Status: Completed
• Conditions: Central Nervous System Diseases; Multiple Sclerosis
• Intervention / Treatment: Other: Biological collection

• Study Type: Observational
• Enrollment (Actual): 1500

Contacts and Locations

Study Locations

• France
  • Clermont-Ferrand, France
    • Centre Hospitalier Universitaire de Clermont-Ferrand
  • Dijon, France
    • Centre Hospitalier Universitaire De Dijon
  • Grenoble, France
    • Centre Hospitalier Universitaire de Grenoble
  • Lille, France
    • Centre Hospitalier Universitaire De Lille
  • Marseille, France
    • Assistance Publique Des Hopitaux de Marseille
  • Montpellier, France
    • Centre Hospitalier Universitaire De Montpellier
  • Nantes, France
    • Centre Hospitalier Universitaire De Nantes
  • Nice, France
    • Centre Hospitalier Universitaire de Nice
  • Nîmes, France
    • Centre Hospitalier Universitaire de Nīmes
  • Paris, France
    • Assistance publique des Hôpitaux de Paris
  • Saint-Étienne, France
    • Centre Hospitalier Universitaire de Saint-Étienne
  • Strasbourg, France
    • Centre Hospitalier Universitaire de Strasbourg
  • Toulouse, France
    • Centre Hospitalier Universitaire De Toulouse
  • Tours, France
    • Centre Hospitalier Régional et Universaitaire de Tours

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients presenting with symptoms evocative of CNS disease

Description

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)

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Mutliple sclerosis	Other: Biological collection; Collection of cerebrospinal fluid kappa and lambda free light chains and indexes
CIS/RIS	Other: Biological collection; Collection of cerebrospinal fluid kappa and lambda free light chains and indexes
Other CNS inflammatory diseases	Other: Biological collection; Collection of cerebrospinal fluid kappa and lambda free light chains and indexes
Non inflammatory CNS diseases	Other: Biological collection; Collection of cerebrospinal fluid kappa and lambda free light chains and indexes

What is the study measuring?

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) / AQKFLC 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

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nice

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 15, 2021
• Primary Completion (ACTUAL): October 31, 2021
• Study Completion (ACTUAL): October 31, 2021

Study Registration Dates

• First Submitted: July 13, 2021
• First Submitted That Met QC Criteria: October 8, 2021
• First Posted (ACTUAL): October 22, 2021

Study Record Updates

• Last Update Posted (ACTUAL): November 9, 2021
• Last Update Submitted That Met QC Criteria: November 8, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: multiple sclerosis; kappa free light chains; lambda free light chains
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Nervous System Diseases; Central Nervous System Diseases
• Other Study ID Numbers: 21Neuro01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No