Effects of Natalizumab Treatment on the Cerebrospinal Fluid Proteome of Multiple Sclerosis Patients
详细信息 查看全文
- 作者：Marcel P. Stoop ; Vaibhav Singh ; Christoph Stingl ; Roland Martin ; Mohsen Khademi ; Tomas Olsson ; Rogier Q. Hintzen ; Theo M. Luider
- 刊名：Journal of Proteome Research
- 出版年：2013
- 出版时间：March 1, 2013
- 年：2013
- 卷：12
- 期：3
- 页码：1101-1107
- 全文大小：232K
- 年卷期：v.12,no.3(March 1, 2013)
- ISSN：1535-3907
文摘
Natalizumab is a very effective, relatively new drug for the treatment of relapsing remitting multiple sclerosis. Inflammatory and neurodegenerative processes in the central nervous system are presumed to cause adverse effects during the course of this disease. To monitor the effects of natalizumab treatment on the cerebrospinal fluid (CSF) proteome of patients, CSF samples were taken from patients before commencing treatment as well as after 1 year of treatment. Profiling proteomics experiments using electrospray Orbitrap mass spectrometry and pair wise comparison of patients before and after 1 year of natalizumab treatment revealed a number of candidate biomarkers that were significantly differentially abundant between the before and after treatment groups. Three proteins were subsequently validated using selected reaction monitoring (SRM) in a new, independent sample set. All three proteins, Ig mu chain C region and haptoglobin, both known inflammation-related proteins, as well as Chitinase-3-like protein 1, were confirmed by SRM to be significantly lower abundant in CSF of multiple sclerosis patients after 1 year of natalizumab treatment. The findings for Chitinase-3-like protein 1, a presumed biomarker for more rapid progression from a first clinically isolated syndrome to clinically definite multiple sclerosis, was further confirmed by ELISA measurements.