Faculty Collaboration Database

Cleavage of cystatin C in the cerebrospinal fluid of patients with multiple sclerosis. Ann Neurol 2006 Feb;59(2):237-47

Date

01/27/2006

Pubmed ID

16437581

DOI

10.1002/ana.20786

Scopus ID

2-s2.0-32044452472 (requires institutional sign-in at Scopus site)   97 Citations

Abstract

OBJECTIVE: The diagnosis of multiple sclerosis (MS) can be challenging because of the lack of a specific diagnostic test. Recent advances in proteomics, however, offer new opportunities for biomarker discovery and the study of disease pathogenesis.

METHODS: We analyzed cerebrospinal fluid (CSF) samples from 29 patients with MS or clinically isolated syndromes (CIS), 27 patients with transverse myelitis (TM), 50 patients with human immunodeficiency virus (HIV) infection, and 27 patients with other neurological diseases (ONDs) by surface-enhanced laser desorption/ionization time-of-flight mass spectroscopy.

RESULTS: We found a unique protein of 12.5 kDa that was 100% specific for MS/CIS compared with TM or OND. Low levels of this protein were found in some patients with HIV infection. Tandem mass spectroscopy of a tryptic digest of this 12.5 kDa protein identified it as a cleavage product of full-length cystatin C (13.4 kDa), an important inhibitor of cysteine proteases including the cathepsins. Although total cystatin C levels in the MS patients was not different compared with controls, the patients with the highest 12.5/13.4 peak ratios also had the greatest cathepsin B inhibitory activity.

INTERPRETATION: This suggests that cleavage of cystatin C may be an adaptive host response and may identify a subgroup of patients with MS.

Author List

Irani DN, Anderson C, Gundry R, Cotter R, Moore S, Kerr DA, McArthur JC, Sacktor N, Pardo CA, Jones M, Calabresi PA, Nath A

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Cathepsins
Cystatin C
Cystatins
Electrophoresis, Polyacrylamide Gel
Female
HIV Infections
Humans
Male
Mass Spectrometry
Middle Aged
Molecular Weight
Multiple Sclerosis
Nervous System Diseases
Protein Array Analysis
Statistics as Topic