Increased ability of peripheral blood lymphocytes to degrade laminin in multiple sclerosis Takeshi Oki a, * , Shunji Takahashi b , Satoshi Kuwabara a , Yasumasa Yoshiyama a , Masahiro Mori a , Takamichi Hattori a , Nobuo Suzuki b a Department of Neurology, Chiba University School of Medicine, 1-8-1 Inohana, Chuo, Chiba 260-8670, Japan b Environmental Biochemistry, Chiba University School of Medicine, Chiba, Japan Received 23 April 2003; received in revised form 5 February 2004; accepted 16 March 2004 Available online 4 June 2004 Abstract T lymphocytes and macrophages probably play a role in the pathogenesis of multiple sclerosis (MS), and migration of these cells into the central nervous system is facilitated by disruption of the capillary basement membrane. Laminin is a major extracellular matrix of the basement membrane. To investigate whether ability of lymphocytes to degrade laminin correlates with disease activity in MS, we conducted a prospective study in consecutive 24 MS patients. A novel quantitative assay was developed to estimate the ability of peripheral blood mononuclear cells (PBMCs) to degrade laminin. The assay was performed every four weeks over a period of 12 months. During the study period, a total of 41 relapses were observed. The ability to degrade laminin was significantly higher in MS patients, even during clinical remission, than in normal and neurological controls, and was transiently increased further within 4 weeks before relapse ( p = 0.076). In MS, the ability of peripheral blood lymphocytes to degrade laminin increases, and may correlate with disease activity. D 2004 Elsevier B.V. All rights reserved. Keywords: Multiple sclerosis; Laminin; Blood– brain barrier; Lymphocyte 1. Introduction In relapsing – remitting multiple sclerosis (MS), disease activity has been suggested to correlate with serum levels of soluble vascular cell adhesion molecule, L-selectin, intracel- lular adhesion molecule-1, and tumor necrosis factor-a receptor. [1–3] Interactions among these adhesion mole- cules and cytokines would facilitate migration of activated T lymphocytes and macrophages from the intravascular com- partment into the central nervous system. In addition to disruption of the blood–brain barrier, migration of these cells is presumably affected by their ability to secrete matrix metalloproteinases (MMPs) and degrade the extracellular matrixes of the basement membrane of the capillaries. [4–6] The major extracellular matrixes of the brain capillaries are reported to be laminin, fibronectin, and collagen type IV. [7] We have developed a novel method to estimate the ability of peripheral blood mononuclear cells to degrade the extracellular matrixes of the capillary basement mem- brane. [8–11] In the hope that the degradation ability might correlate with disease activity and predicts relapse, we conducted a prospective study in consecutive patients with relapsing – remitting MS. 2. Patients and methods 2.1. Patients Twenty-four patients with relapsing–remitting MS (19 female and 5 male; mean age, 36 years), examined at Chiba University Hospital between March 2000 and February 2001, were studied. Their conditions fulfilled Poser’s crite- ria for definite MS. [12] Twenty-nine age-matched healthy subjects and nineteen patients with myasthenia gravis dur- ing the same period served as controls. All patients and healthy subjects gave their informed consent and agreed to participate in the present study. The clinical condition of MS patients was monitored according to the expanded disability status scale (EDSS) every 4 weeks over a period of 12 months. According to 0022-510X/$ - see front matter D 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2004.03.026 * Corresponding author. Tel.: +81-43-222-7171x5414; fax: +81-43- 226-2160. E-mail address: ooki@matsudo-neurology-clinic.or.jp (T. Oki). www.elsevier.com/locate/jns Journal of the Neurological Sciences 222 (2004) 7 – 11