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Cleavage of cystatin C in the cerebrospinal fluid of patients with multiple sclerosis
Author(s) -
Irani David N.,
Anderson Caroline,
Gundry Rebekah,
Cotter Robert,
Moore Stacy,
Kerr Douglas A.,
McArthur Justin C.,
Sacktor Ned,
Pardo Carlos A.,
Jones Melina,
Calabresi Peter A.,
Nath Avindra
Publication year - 2006
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20786
Subject(s) - cystatin c , cerebrospinal fluid , multiple sclerosis , cystatin , neuromyelitis optica , pathogenesis , biomarker , cathepsin b , cleavage (geology) , cathepsin , medicine , immunology , chemistry , biology , gastroenterology , biochemistry , creatinine , enzyme , paleontology , fracture (geology)
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 12.5kDa 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 12.5kDa protein identified it as a cleavage product of full‐length cystatin C (13.4kDa), 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. Ann Neurol 2006;59:237–247