Plasma protein profiling of multiple sclerosis using proximity extension assays

Abstract

AbstractBackgroundMultiple sclerosis (MS) is an inflammatory disease characterized by demyelination and neuro-axonal degeneration in the central nervous system. Except for neurofilament light protein, identification of biomarkers has been difficult to assess in the blood, presumably due partly to sensitivity. To detect traces of disease activities in the periphery and identify low-abundance protein biomarkers, this study conducts an exploratory examination of the plasma proteome of MS using proximity extension technology, a high-sensitivity multiplex PCR-based immunoassay.MethodsA case-control cohort consisting of 52 MS cases (relapsing-remitting=30, progressive=22) and 17 healthy controls were enrolled at the Karolinska University Hospital. EDTA plasma was analyzed for 1157 unique protein targets across thirteen proximity extension assays. Protein associations to disease outcomes and related clinical measures were assessed using a multivariable linear regression model corrected for sex and age at sampling.ResultsAHCY and CHR levels were higher among MS cases than controls, while FABP2 was lower among those with relapsing-remitting disease than controls (Pdiscovery<0.05, Preplication<0.05), although not significant after multiple test corrections. Furthermore, PTN and CYR61 levels were higher in progressive MS than in relapsing-remitting disease (P<0.0002, PFDR<0.05), and CRNN and CXCL13 were associated with more severe disability at sampling (P<0.0001, PFDR<0.05), independent of disease course. CTSF was positively correlated with disease duration (P=4.1×10−5, PFDR=0.044), while RRM2B level correlated with intrathecal immunoglobulin production (IgG Index) in relapsing-remitting MS (P=1.7×10−5, PFDR=0.018).ConclusionWe provide several candidates for characterizing MS, particularly progressive disease, which may help monitor disease progression and treatment response in a clinical setting.