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Cystatin C and cathepsin B in CSF from patients with inflammatory neurologic diseases

From the Departments of Internal Medicine III (Drs. Nagai, Murakawa, Shimode, Umegae, and Kobayashi, and H. Takeuchi) and Biochemistry (Dr. Terashima), Shimane Medical University, Izumo, Japan.

Address correspondence and reprint requests to Dr. Atsushi Nagai, Department of Internal Medicine III, Shimane Medical University, 89-1 Enya-cho, Izumo 693-8501, Japan; e-mail: nagaia{at}shimane-med.ac.jp

BACKGROUND: In CSF, proteolytic enzymes are believed to have crucial roles in the initiation and progression of inflammatory neurologic diseases (IND). Cystatin C, a major cysteine protease inhibitor in CSF, is tightly bound to cathepsin B and H.

OBJECTIVE: To determine if cystatin C is involved in the disease process of IND, the authors measured the cystatin C concentration by ELISA method and cathepsin B and H activities in the CSF of patients with acute IND.

METHODS: Cystatin C concentration and cathepsin B and H activities were measured in CSF samples taken from patients during the acute phase of their disease. Subjects studied were 8 patients with Guillain–Barré syndrome (GBS), 5 with chronic inflammatory demyelinating polyneuropathy (CIDP), 12 with MS, 16 with aseptic meningitis, 15 with neurodegenerative diseases as disease controls, and 35 healthy controls.

RESULTS: A significant decrease in CSF cystatin C level was seen in the patients with GBS, CIDP, and MS compared to the control subjects. High cathepsin B activity, but not cathepsin H activity, was also observed in the patients with GBS, CIDP, and MS.

CONCLUSION: Cystatin C levels in CSF measured by ELISA may help the physician recognize GBS, CIDP, and MS. Decreased levels of cystatin C may be related to the high levels of cathepsin B activity seen in the CSF of patients with GBS, CIDP, and MS.