Cerebrospinal fluid β2-microglobulin in neuro-Behçet’s syndrome

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Abstract

Paired serum and cerebrospinal fluid (CSF) specimens from 17 patients with Behçet’s disease and central nervous system (CNS) involvement (neuro-Behçet’s syndrome; NB) were studied for β2-microglobulin (β2MG) and albumin, using ELISA and single radial immunodiffusion, respectively. We also studied 29 patients with non-inflammatory neurological diseases for comparison. All of CSF β2MG, serum β2MG, Q albumin (an indicator of blood–brain barrier function), and CSF β2MG index (an indicator of intrathecal β2MG synthesis) were significantly elevated in patients with NB compared with the control patients. There were no significant differences in these parameters between 11 patients with chronic NB and six patients with acute NB. In nine patients with NB, CSF β2MG and Q albumin were significantly decreased when the CNS manifestations were improved by successful treatment, whereas CSF β2MG index and serum β2MG were not significantly changed. The results indicate that the elevation of CSF β2MG, which results from the transudation of serum β2MG as well as the increased intrathecal synthesis presumably by infiltrating lymphocytes, is a good marker of CNS disease activity of NB. The data, however, also suggest that the intrathecal synthesis of β2MG might not parallel to the CNS disease activity of NB, most likely due to the recovery of constitutive physiological intrathecal synthesis of β2MG in spite of the withdrawal of pathological β2MG synthesis at times of treatment-associated improvement.

Introduction

Central nervous system (CNS) involvement in Behçet’s disease, usually called neuro-Behçet’s syndrome (NB), is one of the most serious complications of the disease [1], [2]. The neurological involvement is either caused by primary neural parenchymal lesions (neuro-Behçet’s syndrome) or secondary to major vascular involvement [3], [4]. The latter type is rarely complicated with the former type and should be called vasculo-Behçet’s disease [3]. Although a lot of efforts have been made, the etiology and pathogenesis of NB still remain unclear. Previous studies have demonstrated that cerebrospinal fluids (CSF) from patients with NB show characteristic features analogous to those observed in patients with infectious meningoencephalitis (IM), including marked pleocytosis, breakdown of the blood–brain barrier, and elevation of CSF IgM index [5]. Moreover, it has also been disclosed that CSF from patients with active NB have increased levels of interleukin 6 (IL-6) [6], which has been also found to be elevated in CSF from IM [7].

β2-Microglobulin (β2MG) is a low molecular weight protein non-covalently bound to the major histocompatibility complex class I molecule [8]. Previous studies have shown that CSF β2MG was elevated in patients with various neurological diseases, including IM [9], neurosarcoidosis [10], and AIDS dementia complex [11]. However, the kinetics of CSF β2MG have not been fully elucidated in patients with NB. The current studies were therefore designed to explore the levels of β2MG in sera and CSF from patients with NB, in order to delineate the role of β2MG in the pathogenesis of NB.

Section snippets

Patient and samples

The CSF samples were obtained by lumbar puncture from 17 patients with Behçet’s disease (14 males and three females, aged 17–68 years old), who had satisfied the international diagnostic criteria for Behçet’s disease [12]. All the patients also had symptoms or signs of CNS involvement, which were attributed to active Behçet’s disease after careful evaluation (Table 1) [6], [13]. Of the 17 patients, six patients showed acute meningoencephalitis or meningitis as evidenced by the elevation of cell

Results

The concentrations of β2MG in the CSF and sera from patients with NB and control patients are shown in Fig. 1. Both CSF β2MG and serum β2MG were significantly elevated in patients with NB compared with control patients. Of note, CSF β2MG was not correlated with either serum β2MG or Q albumin in control patients, whereas CSF β2MG was significantly correlated with serum β2MG in NB patients (Fig. 2). Although CSF β2MG was not significantly correlated with Q albumin in NB patients, it is likely

Discussion

The current studies disclosed that the levels of β2MG in CSF as well as in sera from patients with NB were significantly elevated compared with control patients. Since there was no other factor that resulted in the elevation of serum β2MG, such as renal damage, the elevation of serum β2MG in NB patients might be related with the systemic disease activity of Behçet’s disease, as is consistent with the previous study [18]. In fact, most of our patients showed recurrent attacks of systemic

Acknowledgements

The authors wish to thank Tomohide Satoh, MD, Chief Professor of Internal Medicine, and Takashi Hashimoto, MD, for encouragement and helpful advice, Tamiko Yanagida, PhD, for technical assistance, and Chise Kawashima for assistance in preparing the manuscript and the illustrations. Supported by 1999 grant (C) 30082142 from the Ministry of Education, Culture, Science and Sports of the Japanese Government.

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