Soluble c-Met in Multiple Sclerosis

The hepatocyte growth factor (HGF)/c-Met pathway plays an important role in several inflammatory conditions, regulating phenotypic plasticity within both myeloid and lymphoid cell populations. c-Met was recently identified as a marker of a distinct subset of highly pro-inflammatory and pro-migratory CD4+ T cells that are enriched in both the blood and cerebrospinal fluid of patients with multiple sclerosis. Soluble c-Met is a cleaved form of the c-Met receptor, released by the disintegrin metalloproteinases ADAM10 and ADAM17. Its role in inflammation is not well understood, and concentrations vary in the blood across different conditions.

In this prospective comparative study, soluble c-Met, HGF, soluble ADAM10/ADAM17, and biomarkers of CNS injury—neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP)—were measured in newly diagnosed, treatment-naïve MS patients (n = 29) and non-inflammatory neurological diseases (NIND) controls (n = 21). Correlations between soluble c-Met and these markers were examined in CSF and plasma.

Soluble c-Met concentrations were significantly higher in both CSF and plasma of MS patients compared with controls, whereas HGF levels did not differ. Among the two proteases, ADAM10 was significantly decreased in plasma of MS patients. In CSF, soluble c-Met correlated positively with NfL (ρ = 0.531, p = 0.011) and GFAP (ρ = 0.525, p = 0.007), while no significant correlations were observed in plasma.

Elevated intrathecal soluble c-Met in MS is associated with markers of neuroaxonal and astroglial injury, suggesting compartment-specific c-Met shedding that may reflect ongoing CNS pathology.

Read the full article: https://doi.org/10.1016/j.jneuroim.2026.578895

WHY IS THIS IMPORTANT?

The study identifies that levels of soluble cMet – a tyrosine kinase receptor expressed in proinflammatory T cells – are increased in both the blood and cerebrospinal fluid (CSF) of newly diagnosed patients with multiple sclerosis (MS). Notably, higher CSF soluble cMet levels were associated with markers of neuronal damage (NfL) and astrocytic injury (GFAP). These findings suggest that soluble c-Met reflects ongoing central nervous system damage. Such biomarkers could help improve early detection of disease activity, monitor progression, and guide treatment decisions in MS.

News