Serum Galectin-3 as a biomarker in acute inflammatory polyradiculoneuropathies: a cohort study

Guillain-Barré Syndrome (GBS) refers to a group of acute inflammatory polyradiculopathies characterized by a diffuse inflammatory attack on the peripheral nervous system, often triggered by a preceding infection. Despite significant progress in both diagnosis and treatment, only a few prognostic systems and useful biomarker have been proposed. In this study, we propose galectin-3 (Gal-3), a novel serum molecule identified expressed by Schwann cells and macrophages, as a potential biomarker with both prognostic and diagnostic significance in patients with GBS.

Serum levels of Gal-3 and neurofilament light chain (NfL) were measured using the Simple Plex cartridge-based immunoassay on the Ella platform (ProteinSimple, San Jose, CA, USA) in serum samples from a cohort of patients with GBS (n = 19) and in a validation cohort of healthy control subjects (n = 13). We also collected data on clinical history and patient outcomes to assess the potential utility of Gal-3 as a diagnostic and predictive biomarker.

Gal-3 levels were significantly higher in patients with GBS (median: 7041 pg/mL; IQR: 5576-8561) compared to healthy controls (median: 5030 pg/mL; IQR: 3877-5998; p < 0.05). Within the GBS cohort, Gal-3 levels were significantly elevated in patients with the axonal variant compared to those with the acute inflammatory demyelinating polyneuropathy (AIDP) variant (median: 8561 pg/mL vs. median: 5998 pg/mL, p < 0.05). A positive correlation was observed between serum Gal-3 levels and NfL levels (ρ = 0.47; p < 0.05). In multivariate logistic regression, log-transformed Gal-3 remained significantly associated with the axonal variant of GBS after adjustment for age at sampling, presence of diarrhea, GBS Disability Score at admission, and log-transformed NfL (β = 3.5, OR = 33, p = 0.048). In ROC curve analysis, Gal-3 demonstrated good discriminatory performance between axonal GBS and AIDP (AUC = 0.84), outperforming NfL (AUC = 0.76). Gal-3 threshold of 6457.5 pg/mL was identified, yielding 100% sensitivity and 61.5% specificity for distinguishing axonal GBS, whereas an NfL threshold of 177.5 pg/mL achieved 83% sensitivity and 84% specificity.

In our cohort, Gal-3 was associated with both diagnostic and prognostic features in patients with GBS. These findings suggest that Gal-3 may serve as a potential biomarker for differentiating axonal subtypes within the GBS spectrum. However, further in vitro and in vivo studies are required to elucidate the cellular source and pathophysiological role of Gal-3 in acute inflammatory polyneuropathies, as well as to evaluate its feasibility and clinical applicability as a biomarker in GBS.