Combined Analysis of Inflammatory Biomarkers for CNS Autoimmune Diseases Diagnostic (CyBIRD)

Evaluation of a Combined Analysis of Serum and Cerebrospinal Fluid Inflammatory Biomarkers to Help in Etiological Diagnosis of Central Nervous System Autoimmune Diseases

Project rationale:

Since 2017, multiple sclerosis diagnosis should match the new McDonald criteria in which a "no better explanation than MS" should be fulfilled. However, many patients present with red flags that lead to a complex diagnostic work-up. There are no available biomarkers that permit to confirm or roll out MS diagnosis in such cases. Therefore, we lack biological markers that can help in the diagnosis of patients presenting with suspected MS.

Many studies have found that serum and cerebrospinal fluid (CSF) cytokines could help to differentiate MS from other diseases such as neuromyelitis optica spectrum disorders (i.e., IL-6) or neurosarcoidosis (i.e., sIL-2R). Serum and CSF kappa free light chains have also shown good diagnosis performance in MS. In daily practice, our MS tertiary center already perform the analysis of CSF concentrations of IL-1β, sIL-2R, IL-6, IL-10, and serum and CSF kappa and lambda free light chains to roll out other central nervous system (CNS) autoimmune diseases in patients presenting with white matter hyperintensities (WMH).

Objective:

To correlate CSF IL-1β, sIL-2R, IL-6, IL-10, serum and CSF kappa and lambda free light chains with the final diagnosis in patients presenting to our MS tertiary center with suspected MS to identify a specific inflammatory biomarker profil involved in MS and other CNS autoimmune diseases.

The methodology:

This is an observational study. All patients ongoing a routine diagnostic work-up for suspected MS from june 2020 to june 2022 in our MS tertiary center will be analyzed. Cerebrospinal fluid IL-1β, sIL-2R, IL-6, IL-10, serum and CSF kappa and lambda free light chains will be correlated with the final diagnosis to ultimately find MS associated biomarkers.

Study Overview

• Status: Recruiting
• Conditions: Central Nervous System Diseases
• Intervention / Treatment: Biological: Data analysis

• Study Type: Observational
• Enrollment (Anticipated): 300

Contacts and Locations

Study Locations

• France
  • Nice, France
    • Recruiting
    • Centre Hospitalier Universitaire de Nice
    • Contact: Michael Levraut, MD; Phone Number: +33492034126; Email: levraut.m@chu-nice.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All patients referred to our MS tertiary center for the diagnostic work-up of white matter hyperintensities suggestive of underlying inflammatory demyelinating disease

Description

Inclusion Criteria:

• Patients referred to our center for the diagnostic work-up of White Matter Lesions
• Patients that need a routine blood analysis
• Patients that need a routine CSF analysis
• Non opposition to research consent

Exclusion Criteria:

• Patients with a contraindication to perform spinal tap (increase bleeding risk medicine or disease)
• Patients with a contraindication to MRI (metal prosthesis…)

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
MS; Patients with a definite MS diagnosis according to the 2017 McDonald criteria	Biological: Data analysis; Analysis of the data from routine care at the end of the diagnostic work-up
Red-flag MS; Patients presenting with clinical, radiological or biological red flags for MS diagnosis who will be ultimately diagnosed as having MS	Biological: Data analysis; Analysis of the data from routine care at the end of the diagnostic work-up
Other CNS autoimmune diseases; Patients with a definite diagnostic of CNS autoimmune disease that is not MS	Biological: Data analysis; Analysis of the data from routine care at the end of the diagnostic work-up
Controls; Patients with a definite diagnostic of non-inflammatory CNS disorder	Biological: Data analysis; Analysis of the data from routine care at the end of the diagnostic work-up

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identify specific biomarkers profil in MS group	Quantification in each group of patients of IL-1beta, soluble receptor of IL-2, IL-6 and IL-10 by ELISA and cerebrospinal fluid/serum kappa and lambda free light chains by using the turbidimetric analyzer Optilite (BindingSite).	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To define the diagnosis performance of "Central vein sign (CVS)" in Radiologically Isolated Syndrome subjects compared to MS patients and patients with WM abnormalities of another origin.	Proportion of CVS positive lesions in each group.	1 day

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nice

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2020
• Primary Completion (Actual): April 1, 2023
• Study Completion (Anticipated): November 1, 2025

Study Registration Dates

• First Submitted: September 16, 2021
• First Submitted That Met QC Criteria: September 16, 2021
• First Posted (Actual): September 24, 2021

Study Record Updates

• Last Update Posted (Actual): April 18, 2023
• Last Update Submitted That Met QC Criteria: April 13, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Nervous System Diseases; Autoimmune Diseases; Central Nervous System Diseases
• Other Study ID Numbers: 21Neuro02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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