Cerebrospinal fluid samples were obtained at lumbar puncture from 53 patients with a wide variety of neurological disorders. Cerebrospinal fluid samples were tested for the presence of P2 protein, a constituent of myelin, with an enzyme linked immunosorbent assay technique using a specific polyclonal antibody. High concentrations of P2 in the cerebrospinal fluid paralleled a raised IgG index (clearance ratio), the presence of oligoclonal bands, as well as raised white cell counts or depressed albumin:IgG ratios. Twenty one patients had been diagnosed as having definite or probable multiple sclerosis and the remaining 32 had other conditions. Of the 13 patients with high positive P2, 12 (92%) were in the multiple sclerosis category; of the 40 patients with low (12) or undetectable (28) P2 concentrations, only nine (23%) were diagnosed as having multiple sclerosis. In this patient population the presence of high immunoreactive P2 concentrations in cerebrospinal fluid was closely associated with evidence of intrathecal immunoglobulin synthesis and with the clinical diagnosis of multiple sclerosis. On this basis it is suggested that immunoassay of P2 concentration in the cerebrospinal fluid may be of potential value in the investigation of patients with demyelinating disorders.

Adolescent↗

PubMed1989

Blood-brain barrier permeability changes during acute allergic encephalomyelitis induced in the guinea pig.

Blood-brain barrier permeability to homologous serum 125I-IgG and to D-[3H]mannitol was studied by means of the brain vascular perfusion method in guinea pigs with experimental allergic encephalomyelitis (EAE). EAE was induced with homologous myelin basic protein (MBP) after pretreatment with foreign protein and muramyl dipeptide (MDP). The results suggest a significant comparable increase in IgG blood-to-brain clearance in the parietal cortex, hippocampus, and caudate nucleus, during vascular perfusion of the brains of animals, after 7 and 20 days of EAE. On the other hand, unidirectional transfer of mannitol in the same period of EAE was markedly augmented only in the hippocampus, but no significant changes in the parietal cortex or caudate nucleus were observed. Cerebrospinal fluid (CSF)/serum ratios for IgG and albumin were both significantly increased, suggesting an increase in blood-CSF barrier permeability, but more for albumin than for IgG. The results were confirmed by immunohistochemical determination of the IgG deposits in the brains of EAE animals, during vascular perfusion with unlabeled homologous IgG. An important role of the blood-brain barrier for the central nervous system immunoglobulin homeostasis during EAE is suggested.

Animals↗

PubMed1988

Immunological and cytological studies of autoimmune demyelination and multiple sclerosis.

The early history of experimental allergic encephalomyelitis is reviewed from the point of view of the characterization and recognition of myelin basic protein and the active agent in acid-fast bacilli, namely muramyl dipeptide. Protocols effective in inducing demyelination are pinpointed. Special attention is paid to the protocol which depends on pretreating guinea pigs with muramyl dipeptide and foreign protein followed by a second injection of foreign protein and then the animals are injected with myelin basic protein and Freund's complete adjuvant. Variations in the timing and amounts of muramyl dipeptide are described as are their effects on the demyelination. The myelin breakdown has been studied with a monoclonal antibody reactive to P2. Similar pretreatment enhances the demyelination in Semliki Forest virus infection in mice. The changes in the blood brain barrier are found at 7 days after the myelin basic protein is injected and show grossly increased uptake by the cerebral vascular endothelium of IgG and perivascular uptake of IgG. The changes in the cerebrospinal fluid (CSF) proteins are described (IgG and albumin). Studies of P2 protein in the CSF by means of a new ELISA technique have been performed on human CSF in multiple sclerosis.

Animals↗

PubMed1987