Inflammation-related plasma and CSF biomarkers for multiple sclerosis

Abstract

Effective biomarkers for multiple sclerosis diagnosis, assessment of prognosis, and treatment responses, in particular those measurable in blood, are largely lacking. We have investigated a broad set of protein biomarkers in cerebrospinal fluid (CSF) and plasma using a highly sensitive proteomic immunoassay. Cases from two independent cohorts were compared with healthy controls and patients with other neurological diseases. We identified and replicated 10 cerebrospinal fluid proteins including IL-12B, CD5, MIP-1a, and CXCL9 which had a combined diagnostic efficacy similar to immunoglobulin G (IgG) index and neurofilament light chain (area under the curve [AUC] = 0.95). Two plasma proteins, OSM and HGF, were also associated with multiple sclerosis in comparison to healthy controls. Sensitivity and specificity of combined CSF and plasma markers for multiple sclerosis were 85.7% and 73.5%, respectively. In the discovery cohort, eotaxin-1 (CCL11) was associated with disease duration particularly in patients who had secondary progressive disease (PCSF< 4 × 10−5,Pplasma< 4 × 10−5), and plasma CCL20 was associated with disease severity (P= 4 × 10−5), although both require further validation. Treatment with natalizumab and fingolimod showed different compartmental changes in protein levels of CSF and peripheral blood, respectively, including many disease-associated markers (e.g., IL12B, CD5) showing potential application for both diagnosing disease and monitoring treatment efficacy. We report a number of multiple sclerosis biomarkers in CSF and plasma for early disease detection and potential indicators for disease activity. Of particular importance is the set of markers discovered in blood, where validated biomarkers are lacking.

Accelerated inflammatory aging in Alzheimer’s disease and its relation to amyloid, tau, and cognition

“…Meanwhile, since CSF-based inflammatory aging correlated strongly with core AD biomarkers and predicted chronological age better than plasma in the main Aβ− CU group, CSF inflammatory proteins likely track more closely with those brain-based inflammatory changes which occur during normal aging. This finding may be explained by higher analytical variability in plasma measurements or the fact that plasma inflammatory protein concentrations are influenced by more abundant proteins found in the periphery 23 . Still, inflammatory proteins measured in plasma are theorized to be a potential source for detecting Alzheimer-related changes based on the idea that AD has a systemic metabolic state which can be observed in the periphery combined with recent improvements in plasma-based assays 24 , 25 .…”

Differential effects on blood and cerebrospinal fluid immune protein markers and kynurenine pathway metabolites from aerobic physical exercise in healthy subjects

“…Data were analyzed using multi-variable linear regression models adjusting for sex and age at sampling, as previously described 28 . In brief, differences in protein and KP metabolite levels pre-/post-intervention across the different exercise groups were analyzed using a paired Student t test.…”

Function of multiple sclerosis-protective HLA class I alleles revealed by genome-wide protein-quantitative trait loci mapping of interferon signalling

“…Data from functional studies demonstrate that, despite presenting with higher IFNAR2 levels, B cells carrying the MS-protective class I alleles have a reduced pSTAT1, pSTAT4 and production of CXCL10 in response to type I IFN stimulation. CXCL10 is a potential biomarker for MS as the levels are elevated in cerebrospinal fluid (CSF) from PwMS and correlate with clinical characteristics such as IgG index, CSF mononuclear counts and T2 lesions [ 47 , 48 ]. A decreased type I IFN response was also evident in CD4 + T and CD8 + T cells carrying the MS-protective class I alleles, but these effects were not as strong as in B cells.…”