Myelin-associated proteins are potential diagnostic markers in patients with primary brain tumour.

INTRODUCTION: Taking into account the possibility of myelin-associated proteins having a role in brain tumour development, the study aimed to evaluate the diagnostic usefulness of myelin-associated proteins (Nogo-A, MAG, OMgp) released into extracellular space in patients with brain tumours. PATIENTS AND METHODS: Protein concentration in primary brain tumour (n = 49) and non-tumoural subjects (n = 24) was measured in cerebrospinal fluid (CSF) and serum by means of ELISA. Immunohistochemistry for IDH1-R132H was done on 5-µm thick formalin-fixed, paraffin-embedded tumour sections with the use of an antibody specific for the mutant IDH1-R132H protein. RESULTS: The receiver operator characteristic curve analysis showed that CSF Nogo-A and serum MAG were useful in differentiating patients with primary brain tumour from non-tumoural individuals. This was also true in the case of the separate analysis of the astrocytic tumour versus non-tumoural groups and the meningeal tumour versus non-tumoural groups. Neither Nogo-A nor MAG or OMgp concentrations were significantly different, in serum or CSF, between IDH1 wild-type astrocytic brain tumour patients compared to IDH1 mutant patients. CONCLUSIONS: Our results indicated the potential usefulness of CSF Nogo-A and serum MAG evaluation as circulating biomarkers of primary brain tumours. Because blood is relatively easy to obtain, future research should be conducted to explicitly indicate the value of serum MAG concentration evaluation as a brain tumour biomarker.Key messagesMyelin-associated proteins may be circulating brain tumour biomarkers.Nogo-A and MAG proteins seem to be the most useful in brain tumour diagnosis.Decreased CSF Nogo-A concentration is an adverse prognostic factor for patients' survival.

Implication of perturbed axoglial apparatus in early pediatric multiple sclerosis.

Cerebrospinal fluid samples collected from children during initial presentation of central nervous system inflammation, who may or may not subsequently be diagnosed as having multiple sclerosis (MS), were subjected to large-scale proteomics screening. Unexpectedly, major compact myelin membrane proteins typically implicated in MS were not detected. However, multiple molecules that localize to the node of Ranvier and the surrounding axoglial apparatus membrane were implicated, indicating perturbed axon-glial interactions in those children destined for diagnosis of MS.

Soluble Nogo-A in CSF is not a useful biomarker for multiple sclerosis.

OBJECTIVE: To determine whether the presence of Nogo-A protein in CSF is a useful biomarker for multiple sclerosis (MS). METHODS: We performed Western blots on CSF from patients with MS and controls with the commercially available Nogo-A antibody and secondary antibody used in a prior report. We used densitometry to measure band density on Western blot. Controls included blots without primary antibody, samples without dithiothreitol (DTT), CSF passed through a protein G column, and Western blots with anti-Ig-light chain antibody. IgG concentration in CSF was measured by ELISA. RESULTS: A band at about 25 kD band was detectable in almost all CSF specimens, but was darker in samples from patients with MS. The density relative to a reference sample (mean +/- SD) was 0.84 +/- 0.67 for relapsing MS (n = 17), 1.16 +/- 0.74 for primary progressive MS (n = 11), and 0.49 +/- 0.22 in controls (n = 12). This band was still present when the primary antibody was omitted, but was absent if the sample buffer did not include DTT or if the CSF was first adsorbed with protein G. IgG concentration was higher in MS CSF and correlated closely with the 25 kD band density (r = 0.78). CONCLUSIONS: A 25 kD band is detectable on Western blots stained with Nogo-A antibody in almost all CSF specimens, but is darker in MS specimens. Our results suggest this band is immunoglobulin light chains rather than Nogo-A. It is not likely to be a useful biomarker for multiple sclerosis.

Soluble Nogo-A, an inhibitor of axonal regeneration, as a biomarker for multiple sclerosis.

BACKGROUND: CNS axons display a poor regenerative response to injury. In multiple sclerosis (MS), failure of damaged axons to regenerate may be a major factor underlying non-reversible neurologic dysfunction. Nogo is a development-related molecule inhibiting axonal regeneration and is a major component of CNS myelin. METHODS: CSF from 114 patients with remitting relapsing MS (RR-MS) and secondary progressive MS (SP-MS) and 153 controls, as well as CNS tissue from 3 patients with MS and 2 controls, were used for this study. RESULTS: We found soluble 20 kDa Nogo-A product in 96% (110/114) of CSF samples from patients with MS compared with 0/18 from meningo-encephalomyelitis, 0/125 from control subjects with other neurologic diseases, and 0/10 from CNS autoimmune diseases. Nogo-A products were present both in RR-MS and SP-MS, as well as in early cases of the disease, but not in neuromyelitis optica. The same Nogo A product was detected in CNS tissue from all patients with MS but not in control CNS tissue. CONCLUSION: Soluble Nogo-A may be specific for the CSF of patients with multiple sclerosis and its presence may predict failure of axonal regeneration within the CNS.

Anti-myelin basic protein and anti-proteolipid protein antibody-secreting cells in the cerebrospinal fluid of patients with acute optic neuritis.

OBJECTIVE: To study the intrathecal synthesis of anti-myelin basic protein (MBP) and anti-proteolipid protein (PLP) antibodies in patients in the early stages of multiple sclerosis. DESIGN AND SETTING: A study of consecutive patients with acute optic neuritis (ON) who were undergoing lumbar punctures in an ambulatory unit. PATIENTS: Eleven patients with acute idiopathic ON and 14 patients with acute ON as a symptom of definite multiple sclerosis (the diagnosis of which was supported by clinical or laboratory findings). Nineteen patients with other neurological diseases (10 with inflammatory diseases) served as controls. MAIN OUTCOME MEASURES: Numbers of anti-MBP and anti-PLP antibody-secreting cells in peripheral blood and cerebrospinal fluid samples that were enumerated with an immunospot assay. RESULTS: Cerebrospinal fluid cells that secreted anti-MBP or anti-PLP antibodies were detected in 10 of 15 and in 21 of 23 patients with acute ON, while they were detected in nine of 18 and in six of 18 patients with other neurological diseases, respectively. Patients with ON had significantly more anti-PLP-secreting cells than did patients with other neurological diseases (P < .01). No difference was observed for anti-MBP-secreting cells. A significant correlation between the time from onset and the number of anti-PLP-secreting cells was found in patients with idiopathic ON (P < .02). CONCLUSIONS: These data suggest that anti-PLP antibodies are a more specific finding in demyelinating disease than anti-MBP antibodies. Furthermore, they suggest that anti-PLP antibodies may arise as a consequence of the demyelinating process.

[Determination of IgG subclass antibodies to the basic myelin protein in patients with multiple sclerosis]. / Badania nad okresleniem podklas IgG przeciwcial przeciwko bialku zasadowemu mieliny u pacjentów ze stwardnieniem rozsianym.

The aim of the study was to determine IgG subclasses of MBP antibodies in patients with multiple sclerosis. The enzyme-linked immunosorbent assay (ELISA) with monoclonal antibodies against human IgG subclasses was applied. Anti-MBP antibodies were found in the CSF of 16% and in the sera of 20% patients with MS. MBP antibodies belonged to IgG1, IgG2 and IgG3 subclasses (in the CSF) and to IgG1 and IgG3 subclasses (in the sera). The role of MBP antibodies in context of their IgG subclasses distribution is discussed.

[Thoracic radiation myelopathy]. / Popromienna mielopatia piersiowa.

In a 62-year-old patient 8 month after radiotherapy for right pulmonary hilus carcinoma signs of thoracis cord involvement with ascending course from Th10 to Th7. Cerebrospinal fluid and myelogram were normal. The patient died after about 12 months. Radiation myelopathy was confirmed by neurohistological examination. The results of experimental studies are quoted which could predict the possibility of early diagnosis of radiation myelopathy by rising level of basic myelin protein in cerebrospinal fluid.

Antibodies to myelin-associated glycoprotein are found in cerebrospinal fluid in polyneuropathy associated with monoclonal serum IgM.

Antibodies to myelin-associated glycoprotein (MAG) have been demonstrated in the serum samples from about half the patients with polyneuropathy associated with serum IgM monoclonal component. We examined cerebrospinal fluid (CSF) and serum samples from 13 patients with this disease by enzyme-linked immunosorbent assay for anti-MAG IgM antibodies. We detected these antibodies in both CSF and serum samples in 10 of the patients; in three of them the antibodies were at higher levels in the CSF. The remaining three patients had anti-MAG IgM antibodies in the CSF only. Intrathecal production of anti-MAG IgM antibodies is thus common in polyneuropathy associated with IgM monoclonal component. In three patients, examined on two occasions from 1 to 7 years, high anti-MAG IgM antibody levels persisted in CSF and serum samples. Among 165 patients with other neurologic diseases, including 60 with multiple sclerosis and 60 control subjects with tension headache, anti-MAG IgM antibodies were detected in the CSF from three patients (two with multiple sclerosis, one with aseptic meningitis), and in the serum sample of one patient with multiple sclerosis. Whether the frequent occurrence of anti-MAG IgM antibodies in CSF and their intrathecal synthesis has pathogenetic relevance for the development of polyneuropathy associated with IgM monoclonal component is unsure.

Visual evoked potentials in patients with neuropathy and macroglobulinemia.

Visual evoked potentials were studied in 11 patients with neuropathy and macroglobulinemia. The P100 latency was increased bilaterally in 5 of the 6 patients whose IgM M-proteins reacted with myelin-associated glycoprotein (MAG) and in 1 of the other patients. In patients whose M-protein bound to MAG, abnormal visual evoked potentials correlated with the presence of the M-protein in the cerebrospinal fluid. Subclinical involvement of the central nervous system is frequent in patients with neuropathy and anti-MAG M-proteins and may be due to the binding of M-proteins to central nervous system myelin.

Failure to detect anti-MAG antibodies by RIA in CSF of patients with multiple sclerosis.

Using a sensitive double-antibody radioimmunoassay (RIA) we measured IgG antibodies to the myelin-associated glycoprotein (MAG) in cerebrospinal fluid (CSF) of patients with active multiple sclerosis (MS) and with other neurological diseases (OND). Comparable levels of precipitation of radiolabeled MAG were obtained with CSF from the patients of the two groups.

A derivative of myelin-associated glycoprotein in cerebrospinal fluid of normal subjects and patients with neurological disease.

A procedure for quantitating the myelin-associated glycoprotein (MAG) in cerebrospinal fluid (CSF) was developed. The procedure involved immunoprecipitation with rabbit polyclonal anti-MAG antiserum followed by immune staining of electroblots with the monoclonal antibody HNK-1. This method could detect as little as 2 ng of MAG per ml of CSF and could accurately measure levels of 5 ng/ml or greater. No intact MAG was detected in any of the CSF samples examined, but all samples contained the 90K dalton proteolytic derivative of MAG called dMAG. Samples from normal volunteers and patients with demyelinating diseases contained levels of dMAG ranging from 2 to 13 ng/ml. There was no correlation of dMAG levels with levels of myelin basic protein or with active demyelinating disease. The relatively high levels of dMAG, even in control CSF samples, probably resulted from normal physiological turnover of MAG and could possibly obscure any additional increments of MAG or dMAG release that might occur as a result of demyelination.

Cerebrospinal fluid myelin basic protein as a prognostic marker in patients with head injury.

Despite increasing interest in identifying biochemical and serologic markers to judge the severity of closed head injury in comatose patients, clinical variables remain the most readily available methods for assessing prognosis. In a series of 35 severely head-injured comatose patients, the cerebrospinal fluid (CSF) level of myelin basic protein (MBP) was analyzed by radioimmunoassay. MBP levels during the first week after injury were significantly correlated with the Glasgow outcome score at 7 days (p less than .005), 3 months (p less than .005), and 6 months (p less than .05) postinjury. Measurement of CSF MBP appears to be a useful laboratory adjunct to clinical assessment, for judging the outcome of severely head-injured patients.

Proteína básica de Mielina no líquido cefalorragueano na neurocisticercose / Myelin basic protein in cerebrospinal fluid in neurocysticercosis

Foram estudadas 133 amostras de LCR provenientes de 115 pacientes para verificar o teor da PBM, fragmento P1 43-88. Os casos foram subdivididos em subgrupos de acordo com o diagnóstico nosológico. No grupo controle (50 casos de pacientes com cefaléia crônica) näo houve detecçäo de PBM em qualquer das amostras; dos casos de neurocisticercose (44), em 4 havia presença da PBM; nos de esclerose múltipla (8) em três havia PBM; em um caso de neuroesquistossomose, forma medular, também foi detectada a presença da PBM. Consideraçöes de ordem neuroimunológica säo tecidas sobre os resultados encontrados

The influence of high-dose prednisone medication on autoantibody specific activity and on circulating immune complex level in cerebrospinal fluid of multiple sclerosis patients.

In agreement with the close correlation between intrathecal IgG production and anti-MBP (myelin basic protein) and anti-MAG (myelin-associated glycoprotein) antibody activity in the CSF of active MS cases, and parallel to the reduction of intrathecal IgG synthesis resulting from corticosteroids medication, we have found a significant reduction of anti-MBP and anti-MAG antibody activity expressed per 0.5 micrograms of CSF IgG in the same group of 40 MS patients subjected to high-dose prednisone therapy. Every patient received 3980 mg of prednisone over 54 days. In native CSF of 30% (21/70) of active MS cases, circulating immune complexes (CIC) were detected by C1q binding solid-phase RIA. There was no correlation between CIC level in the CSF or MS patients and 1. IgG index which was used as an indicator of intrathecal IgG synthesis, or 2. CSF anti-MBP specific antibody activity, or 3. CSF anti-MAG specific antibody activity. High-dose prednisone therapy resulted in a highly significant reduction of the CSF CIC level. CIC were also found in the CSF of patients affected with various chronic diseases of the CNS.

Myelin basic protein in cerebrospinal fluid from children.

Forty-one cerebrospinal fluid (CSF) specimens from children were investigated with a radioimmunoassay for their content of myelin basic protein (BP). Eight specimens were regarded as BP-positive (BP is greater than or equal to 1.0 ng/ml). Twenty-nine were BP-negative and 4 could not be analyzed because of an excessive protein content. The BP-positive samples were from 6 children with evidence of severe acute brain damage leading to death in 5 cases: i.e., 2 term newborns with perinatal asphyxia, a 4 week-old child with severe convulsions, a 3 year-old boy with hypoxia due to laryngitis, and a 12 year-old girl with encephalitis. One preterm baby survived severe hypoxia and developed hydrocephalus shortly afterwards. We conclude that BP becomes detectable in CSF of newborns and older children under certain pathological conditions, and that the presence of BP in CSF may be associated with severe brain tissue destruction.