Interleukin-12p40 in the spinal fluid as a biomarker for clinically isolated syndrome

Abstract

Background:

The cerebrospinal (CSF) constitutes a specific immune micro-environment to the central nervous system, thus it may contain specific biomarkers involved in the pathogenesis of multiple sclerosis (MS).

Objectives:

We aimed to study a large array of inflammatory CSF biomarkers in patients with suspected MS to recognize potential early diagnostic markers.

Methods:

CSF samples were obtained from 115 patients who presented with neurological symptomatology suggestive of MS as follows: clinically isolated syndrome (CIS) = 49, relapsing–remitting multiple sclerosis (RRMS) = 29, and other neurologic disorders (OND) = 37. Protein expression profiles of 30 inflammatory biomarkers were measured by multiplex Luminex bead assay and further analyzed by group comparison statistics, correlation studies and receiver-operating characteristic (ROC) analysis.

Results:

Interleukin-12 subunit p40 (IL12p40) demonstrated a significant differential expression pattern between the groups (CIS vs OND: p = 1.17*10⁻⁷; RRMS vs OND: p = 4.98*10⁻⁵), with higher levels in CIS and RRMS patients. ROC analysis demonstrated excellent diagnostic performance of IL12p40 for discrimination between CIS and OND patients (area under the curve = 0.87 (95% CI 0.78–0.93), p = 0.0001). No associations were found with disease activity or severity measures.

Conclusions:

An increased IL12p40 level characterizes the CSF of MS patients and appears to be helpful in identifying CIS and OND patients early in the process of clinical diagnostic assessment.

Keywords

Multiple sclerosis immunology clinically isolated syndrome cerebrospinal fluid biological markers interleukin-12 subunit p40

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