Cerebrospinal fluid markers of demyelination: MBP and anti-brain protein antibodies

Abstract

In multiple sclerosis (MS), an inflammatory mechanism leads to demyelination and release of myelin proteins. The destroyed myelin is engulfed by macrophages as vesicular material. One of the most studied proteins is myelin basic protein (MBP), which constitutes about 30% of the protein component of central nervous system myelin: it is capable of inducing experimental allergic encephalomyelitis (EAE), an animal model close to MS pathology. MBP has been detected in the cerebrospinal fluid (CSF) of patients with MS during acute exacerbation up to two weeks after clinical onset, and is considered a reliable indicator of acute demyelination [1–3]. The MBP-like material detected in MS CSF has been extensively studied. By means of antisera recognizing different epitopes of the molecule, it was found that MBP circulating in CSF is a fragment containing an epitope corresponding to aminoacid residues 45–89 and that peptide 80–89 is the smallest sequence containing the dominant epitope [4]. The MBP epitope detected in CSF was found to be different from that in the urine of MS patients which corresponds to peptide 82–89 [5]. These findings suggest that MBP fragments released during myelin breakdown undergo enzymatic modification in the blood and additionally in the kidneys. They also contribute to understanding of the mechanism underlying MBP processing and how humoral and cellular immune responses directed against myelin proteins are elicited.