Serum GFAP and NfL levels in benign relapsing-remitting multiple sclerosis

●Fluid biomarkers may help clinicians to evaluate the activity and progression of MS.●Serum GFAP levels are elevated also in patients with benign disease course.●Serum NfL levels were found similar in benign and aggressive phenotype of RRMS.●Benign label for RRMS should be used cautiously, not as a synonym for inactive MS.●Single serum NFL and GFAP measurement cannot be used to determine the type of disease. We aimed to investigate serum glial fibrillary acidic protein (GFAP) and serum neurofilament light chain (NfL) levels as potential discriminative biomarkers between benign relapsing-remitting multiple sclerosis (BRRMS) and aggressive relapsing-remitting MS (ARRMS). Serum GFAP and NfL levels were analyzed in patients with BRRMS (n = 34), ARRMS (n = 29), and healthy controls (n = 14) by using Single Molecule Array (Simoa). Patients with ARRMS had been treated with highly effective disease-modifying treatments (DMT) (fingolimod or natalizumab). Serum GFAP levels in both BRRMS (median 210.19 pg/ml, IQR 163.69–287.19) and in ARRMS (median 188.60 pg/ml, IQR39.23–244.93) were significantly higher (p = 0.035 and p = 0.034, respectively) compared to healthy controls (median 117.93 pg/ml, IQR 60.28–183.83). Serum GFAP levels did not differ between BRRMS and ARRMS. There were no statistical differences in NfL levels between BRRMS, ARRMS and healthy controls. GFAP level was significantly higher (p = 0.04) in BRRMS without DMT (median 216.04 pg/ml, IQR 188.60–274.79) than in those BRRMS patients who had used DMT (median 196.26 pg/ml, IQR 133.33–325.54). We found elevated levels of serum GFAP in both BRRMS and ARRMS compared to healthy controls, reflecting astrocytic activation. Serum NfL did not differ between BRRMS and ARRMS, probably due to the stable inflammatory phase of the disease and effective DMT use in ARRMS. Single serum NfL and GFAP measurements cannot separate a patient with BRRMS from effectively treated ARRMS after a long history of the disease, thus consecutive samples are needed in the follow-up.