# Impact of preanalytical factors on blood CHI3L1 levels

## TL;DR

This study examines how blood handling affects CHI3L1 levels, a potential biomarker for multiple sclerosis, and finds that blood levels correlate with spinal fluid levels.

## Contribution

The study identifies classical monocytes as the main source of CHI3L1 in blood and establishes preanalytical stability guidelines for its measurement.

## Key findings

- Serum CHI3L1 levels remain stable after 6 hours of delayed processing and three freeze-thaw cycles.
- CHI3L1 levels in serum, plasma, and cerebrospinal fluid are strongly correlated.
- Classical monocytes (CD14++CD16- cells) are the primary producers of CHI3L1 in peripheral blood mononuclear cells.

## Abstract

Chitinase 3-like 1 (CHI3L1) is a prognostic biomarker in multiple sclerosis (MS). However, its clinical application is limited by a lack of standardized detection methods and concerns about preanalytical variability.

This study aims to evaluate the impact of preanalytical factors (delayed processing of blood and repeated thawing/freezing) on serum CHI3L1 levels. Additionally, we sought to correlate CHI3L1 blood and cerebrospinal fluid (CSF) levels and identified its cellular source in peripheral blood mononuclear cells (PBMCs) from MS patients.

We used an in-house Single Molecule Array (Simoa) assay to measure CHI3L1 levels in serum, plasma, and CSF from MS patients and controls. The source of CHI3L1 production in PBMCs was determined by flow cytometry.

A strong correlation was found between serum, plasma, and CSF CHI3L1 levels. Serum CHI3L1 levels remained stable with delayed processing up to 6 hours and for up to three freeze-thaw cycles. Monocytes, particularly classical monocytes (CD14++CD16- cells), were identified as the main producers of CHI3L1 in PBMCs.

The study establishes preanalytical guidelines for sCHI3L1 assessment and confirms that blood levels can be as informative as CSF levels. This provides groundwork for the standardized use of CHI3L1 as a biomarker in managing MS patients.