Patients with progressive multiple sclerosis (MS) have higher levels of protein markers of activated glial cells than those with relapsing-remitting MS (RRMS) or patients with other neurological disorders, according to a new study.
The findings also indicated that scoring the extent of glial involvement in relation to nerve cell damage in serum may help differentiate these two groups of MS patients.
The research, “Markers of glial processes and axonal damage in CSF and serum help to differentiate between relapsing-remitting and progressive forms of MS,” was presented by André Huss, PhD, from University Hospital Ulm, Germany, at the 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held in Stockholm Sept. 11-13.
Glial fibrillary acidic protein (GFAP) is a marker of astrocytes — cells involved in the provision of nutrients to neurons, repair of nervous tissue following injury, and facilitation of neurotransmission.
Recent work found that the serum levels of this protein are associated with disease severity in primary progressive MS, while those in the cerebrospinal fluid (CSF; the liquid surrounding the brain and spinal cord) are linked with disease duration in the same patient population.
Also, CSF levels of GFAP correlate with markers of nerve cell damage, such as neurofilament light chain (NfL).
In turn, another study found that GFAP levels, but not those of NfL, were higher in progressive than in relapsing MS patients.
Aiming to better determine the involvement of glial cells in the nervous system — such as astrocytes — and the extent of nerve cell damage in different subtypes of MS, a research team in Germany measured the levels of GFAP and CHI3L1 — a protein marker of activated immune cells — in comparison to NfL in patients with RRMS and progressive MS.
A total of 86 patients were included, 47 with RRMS and 39 with progressive disease, as well as 20 controls with other neurological diseases. To measure NfL and GFAP levels, the scientists used the Simoa assay (by Quanterix).
Results showed that GFAP levels were higher in the CSF and serum of progressive MS patients than in people with RRMS and controls. In turn, CSF and serum amounts of NfL were higher in both groups with MS compared with the controls, but not different when comparing relapsing with progressive disease.
As for CHI3L1, its CSF levels were higher in progressive MS patients than in the RRMS and control groups, and higher in RRMS patients than in controls. Serum CHI3L1 concentration was higher in people with progressive MS compared to the controls.
A subsequent analysis calculated the “Glia-score” — multiplying the levels of CHI3L1 by those of GFAP, then dividing by the amount of NfL — to reflect the extent of glial cell involvement in relation to nerve cell damage.
“The higher the Glia score is, the more axonal damage is present in patients,” Huss said.
In both CSF and serum, this score was higher in progressive MS patients compared to both RRMS patients and controls. Also, as assessed through the Expanded Disability Status Scale (EDSS), the Glia score in serum correlated with disability in the progressive MS group, but not in the RRMS group. Such a link was not found in the CSF.
“Glia score and CHI3L1 show a moderate correlation with EDSS but only in serum, and only in progressive MS but not in RRMS patients,” Huss said. Based on the results, the researcher suggested that “GFAP and CHI3L1 are helpful markers in progressive MS patients.”
Overall, Huss concluded that the data obtained “indicate the involvement of glial mechanisms during the pathogenesis of progressive MS,” and that the Glia score “might help in differentiating progressive disease and RRMS.”
The researcher and his team plan to further investigate serum biomarkers in neurological diseases, and how they correlate with levels in CSF, to better understand the underlying mechanisms for the production of GFAP and CHI3L1.