Serum Neuroinflammatory Disease-Induced Central Nervous System Proteins Predict Clinical Onset of Experimental Autoimmune Encephalomyelitis

Frontiers in Immunology

卷:8

Thomas G. Forsthuber¹  Johanna Webb¹  Carol A. Chase Huizar¹  Bernard P. Arulanandam¹  Yufeng Wang¹  Rishein Gupta¹  Francisco Gomez-Rivera¹  William E. Haskins¹  Itay Raphael² 

[1] Department of Biology, University of Texas at San Antonio, San Antonio, TX, United States;

[2] Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, United States;

关键词: predictive biomarkers;    multiple sclerosis;    experimental autoimmune encephalomyelitis;    T cell;    central nervous system protein;    serum expression;   

DOI  :  10.3389/fimmu.2017.00812

来源: DOAJ

【 摘 要 】

There is an urgent need in multiple sclerosis (MS) patients to develop biomarkers and laboratory tests to improve early diagnosis, predict clinical relapses, and optimize treatment responses. In healthy individuals, the transport of proteins across the blood–brain barrier (BBB) is tightly regulated, whereas, in MS, central nervous system (CNS) inflammation results in damage to neuronal tissues, disruption of BBB integrity, and potential release of neuroinflammatory disease-induced CNS proteins (NDICPs) into CSF and serum. Therefore, changes in serum NDICP abundance could serve as biomarkers of MS. Here, we sought to determine if changes in serum NDICPs are detectable prior to clinical onset of experimental autoimmune encephalomyelitis (EAE) and, therefore, enable prediction of disease onset. Importantly, we show in longitudinal serum specimens from individual mice with EAE that pre-onset expression waves of synapsin-2, glutamine synthetase, enolase-2, and synaptotagmin-1 enable the prediction of clinical disease with high sensitivity and specificity. Moreover, we observed differences in serum NDICPs between active and passive immunization in EAE, suggesting hitherto not appreciated differences for disease induction mechanisms. Our studies provide the first evidence for enabling the prediction of clinical disease using serum NDICPs. The results provide proof-of-concept for the development of high-confidence serum NDICP expression waves and protein biomarker candidates for MS.

【 授权许可】

Unknown