BACKGROUND The added value of neurofilament light chain levels in serum sNfL to the concept of no evidence of disease activity 3 NEDA 3 has not yet been investigated in detail OBJECTIVE To assess whether combination of sNfL with NEDA 3 status improves identification of patients at higher risk of disease activity during the following year METHODS We analyzed 369 blood samples from 155 ear
BACKGROUND: Increased blood brain barrier (BBB) permeability, CNS inflammation and neuroaxonal damage are pathological hallmarks in early multiple sclerosis (MS). OBJECTIVE: To investigate the associations of neurofilament light chain (NfL) levels with measures of BBB integrity and central nervous system (CNS) inflammation in MS during the first demyelinating event. METHODS: Blood and cerebrospinal fluid (CSF) were obtained from 142 MS (McDonald 2017) treatment-naive patients from the SET study (63% female; age: 29.7 ± 7.9 years) following the disease onset. NfL, albumin, immunoglobulin G (IgG), and immunoglobulin M (IgM) levels were measured in CSF and blood samples. Albumin quotient was computed as a marker of BBB integrity. Immune cell subset counts in CSF were measured using flow cytometry. MS risk factors, such as Human leukocyte antigen DRB1 locus gene (HLA DRB1)*1501, anti-Epstein-Barr virus (EBV) antibodies, and 25-hydroxy vitamin D3, were also measured. RESULTS: Higher serum NfL (sNfL) levels were associated with higher albumin quotient (p < 0.001), CSF CD80+ (p = 0.012), and CD80+ CD19+ (p = 0.015) cell frequency. sNfL levels were also associated with contrast-enhancing and T2 lesions on brain magnetic resonance imaging (MRI; all p ⩽ 0.001). Albumin quotient was not associated with any of the MS risk factors assessed. sNfL levels were associated with anti-EBV viral capsid antigen (VCA) IgG levels (p = 0.0026). CONCLUSION: sNfL levels during the first demyelinating event of MS are associated with greater impairment of BBB integrity, immune cell extravasation, and brain lesion activity on MRI.
- MeSH
- biologické markery MeSH
- dospělí MeSH
- hematoencefalická bariéra * MeSH
- intermediární filamenta MeSH
- lidé MeSH
- lymfocyty MeSH
- mladý dospělý MeSH
- neurofilamentové proteiny MeSH
- rizikové faktory MeSH
- roztroušená skleróza * MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVE: To determine whether serum neurofilament light chain (sNfL) levels are associated with recent MRI activity in patients with relapsing-remitting MS (RRMS). METHODS: This observational study included 163 patients (405 samples) with early RRMS from the Study of Early interferon-beta1a (IFN-β1a) Treatment (SET) cohort and 179 patients (664 samples) with more advanced RRMS from the Genome-Wide Association Study of Multiple Sclerosis (GeneMSA) cohort. Based on annual brain MRI, we assessed the ability of sNfL cutoffs to reflect the presence of combined unique active lesions, defined as new/enlarging lesion compared with MRI in the preceding year or contrast-enhancing lesion. The probability of active MRI lesions among patients with different sNfL levels was estimated with generalized estimating equations models. RESULTS: From the sNfL samples ≥90th percentile, 81.6% of the SET (OR = 3.4, 95% CI = 1.8-6.4) and 48.9% of the GeneMSA cohort samples (OR = 2.6, 95% CI = 1.7-3.9) was associated with radiological disease activity on MRI. The sNfL level between the 10th and 30th percentile was reflective of negligible MRI activity: 1.4% (SET) and 6.5% (GeneMSA) of patients developed ≥3 active lesions, 5.8% (SET) and 6.5% (GeneMSA) developed ≥2 active lesions, and 34.8% (SET) and 11.8% (GeneMSA) showed ≥1 active lesion on brain MRI. The sNfL level <10th percentile was associated with even lower MRI activity. Similar results were found in a subgroup of clinically stable patients. CONCLUSIONS: Low sNfL levels (≤30th percentile) help identify patients with MS with very low probability of recent radiologic disease activity during the preceding year. This result suggests that in future, sNfL assessment may substitute the need for annual brain MRI monitoring in considerable number (23.1%-36.4%) of visits in clinically stable patients.
- MeSH
- dospělí MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- mladý dospělý MeSH
- neurofilamentové proteiny krev MeSH
- progrese nemoci * MeSH
- relabující-remitující roztroušená skleróza krev diagnóza patologie MeSH
- senzitivita a specificita MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- práce podpořená grantem MeSH
