Anti-GFAP antibodies in the cerebrospinal fluid of patients with multiple sclerosis and other neurologic diseases

The antibodies against glial fibrillary acidic protein (GFAP) in the CSF of patients with multiple sclerosis and other neurological diseases were determined. It was shown that the binding activity of CSF IgG with GFAP was higher in patients with MS and other organic neurological diseases as compared to control group (neurotics). The results support the idea, that in SM there is a general immune dysregulation, leading to production of a variety of autoantibodies against different antigens, including the presently shown GFAP.     

Neutral protease in cerebrospinal fluid from patients with multiple sclerosis and other neurological diseases

Neutral protease activity was significantly elevated in the cerebro-spinal fluid of patients with multiple sclerosis (MS) in exacerbation and in the acute phase of acute viral meningoencephalitis (AME) compared with that of MS in remission, amyotrophic lateral sclerosis or psychosomatic disease. Since in each relapse of MS, protease activity was higher in exacerbation than in remission, this activity may be one good marker of disease activity in MS. One hundred micro molar of FOY305, synthetic protease inhibitor, inhibited in vitro increased neutral protease activity in MS in exacerbation, which suggests the possibility of a clinical application of this protease inhibitor for MS.     

Myelin basic protein in cerebrospinal fluid of patients with multiple sclerosis and other neurological diseases

Summary Cerebrospinal fluid (CSF) from 105 patients was analyzed by radio-immunoassay for the presence of material cross-reactive with peptide 89–169 of bovine myelin basic protein (BP).In a group of 72 multiple sclerosis patients, 52 showed higher BP content than the control group, i.e. more than 2 ng/ml CSF. Increased BP or BP fragments could be detected in CSF from almost all patients who recently (within 2 weeks) had had an acute episode, or after deterioration in the progressive form of the disease. Fifteen to 30 days after the onset of exacerbation or in a stable period, BP content decreases and in the slowly progressive form was in the range of the control group with one exception.BP content was also elevated in the CSF of patients with other neurological diseases. The presence of BP in the CSF from patients with isolated retrobulbar neuritis is of particular interest. Thus the presence of material cross-reactive with BP fragment 89–169 is not specific for multiple sclerosis, but is a useful parameter in diagnosis and evaluation of MS.

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Zusammenfassung Mit Hilfe eines Radioimmunoassays wurde der Liquor von 105 Patienten auf Substanzen untersucht, die mit dem Fragment 89–169 des bovinen basischen Myelinproteins (BP) kreuzreagieren. Von 72 Patienten mit Multipler Sklerose hatten 52 einen höheren BP-Gehalt im Liquor als die Kontrollgruppe, d.h. mehr als 2 ng/ml. Dies war bei fast all jenen Patienten der Fall, bei denen der Liquor innerhalb von 2 Wochen nach einem akuten Schub bzw. zum Zeitpunkt einer deutlichen Verschlechterung des Zustandes bei der chronisch-progredienten Form gewonnen wurde. Der BP-Gehalt des Liquors nimmt zwischen dem 15. und 30. Tag nach Schubbeginn deutlich ab. In der schleichenden progredienten Form wurde mit einer Ausnahme kein erhöhter BP-Gehalt gefunden.Das basische Myelinprotein ist aber auch im Liquor von Patienten mit anderen neurologischen Erkrankungen zu finden. Hervorzuheben ist das Auftreten von BP im Liquor von Patienten mit Retrobulbär-neuritis.Der Nachweis von mit Bruchstück 89–169 kreuzreagierenden Substanzen im Liquor ist infolgedessen zwar nicht spezifisch für die Multiple Sklerose, ist aber ein wertvoller Parameter in der Diagnose und Einschätzung der MS.

     

Soluble immune complexes in cerebrospinal fluid of patients with multiple sclerosis and other neurological diseases

The occurrence of soluble immune complexes (IC) in the cerebrospinal fluid (CSF) of 14 multiple sclerosis (MS) patients, four acute polyradiculoneuritis patients, 30 patients with other neurological diseases (OND) and 30 patients with disc prolapse (DP) was examined by a solid phase C1q-protein A binding assay (C1q-PABA) and a complement consumption test. IC-positive reactions were observed only in the C1q-PABA. The binding indices determined by the C1q-PABA differed significantly ( P < 0.01) when the MS or the OND patient groups were compared to the DP group. No significant ( P < 0.1) difference was observed between the indices in the MS and OND groups. Binding indices in C1q-PABA showed no correlation either to IgG concentration, total protein concentration or cell counts in CSF of MS patients. Three of the four polyradiculoneuritis patients were strongly IC-positive while the fourth patient was negative. Filtration and PEG-precipitation data indicated that a major part of the IgG-containing IC in CSF detected by C1q-PABA was of macromolecular nature.     

Immune complexes in serum and cerebrospinal fluid of multiple sclerosis patients and patients with other neurological diseases

Paired serum and cerebrospinal fluid (CSF) specimens from 30 multiple sclerosis (MS) patients and 30 patients with other neurological diseases (ONDs) were analyzed for the presence of immune complexes (ICs). With each of the 4 tests used, ICs were found more frequently in sera from both MS and OND patients than in sera from healthy blood donors. IC-positivity for MS and OND patient CSF varied from 10-33 % and from 10-17 % in different tests. The number of IC-positive sera or CSF in MS patients did not differ significantly from those in OND patients. For both MS and OND patients, the positivity pattern for serum and CSF specimens in each IC test was essentially unique. Furthermore, because several CSF IC-positive and serum IC-negative paired specimens were found, intrathecal IC formation may be independent of IC formation in peripheral blood. The presence of ICs in serum or CSF did not correlate with the clinical status of or laboratory data on the MS patients, nor was a correlation found with the diagnosis of the OND patients. In total, these results suggest that the presence or absence of ICs in MS or OND patients may simply reflect changes in the immunological regulation of individual patients.     

Analysis of Chlamydia pneumoniae-specific oligoclonal bands in multiple sclerosis and other neurologic diseases

OBJECTIVE: Paired serum and cerebrospinal fluid (CSF) specimens were investigated for Chlamydia pneumoniae-specific oligoclonal bands (OCBs) to determine band specificity in multiple sclerosis (MS). MATERIAL AND METHODS: Serum and CSF samples were collected from patients with relapsing-remitting MS (n = 56), other inflammatory (n = 18) or non-inflammatory (n = 15) neurologic diseases, and from 10 healthy controls. OCBs were determined with affinity immunoblotting of C. pneumoniae-specific IgG onto antigen-coated nitrocellulose paper after protein separation with agarose isoelectric focusing. RESULTS: Chlamydia pneumoniae-specific OCBs were present in 5 of 56 patients with MS, and in 3 of 18 patients with other inflammatory neurologic diseases. CONCLUSIONS: The intrathecal production of C. pneumoniae-specific oligoclonal IgG occurs in a minority of patients with MS. This intrathecal anti-C. pneumoniae reactivity is likely part of a polyspecific humoral immune response in MS.     

Cerebrospinal fluid cells in multiple sclerosis and other neurological diseases: an immunocytochemical study

Summary Determinations of mononuclear cell subsets in cerebrospinal fluid (CSF), using monoclonal antibodies against surface antigens which identified pan T-cells, helper/inducer T-cells, cytotoxic/suppressor T-cells and Ia-positive cells, were performed in patients with multiple sclerosis (MS), other neuroimmunological diseases (NID), infectious diseases (INF) of the central nervous system and with other neurological diseases. Whereas there was an elevated helper T/suppressor T ratio in CSF of patients with NID (Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, cerebral vasculitis), no other significant differences could be detected between the different groups of patients. Our results suggest that analysis of these mononuclear cell subsets in CSF is not helpful in discriminating between MS and other neurological diseases and that in MS patients changes in disease activity are not clearly indicated by fluctuations in the different CSF cell subsets. Further studies will be needed to confirm our findings in NID patients and to understand the diagnostic and theoretical implications.     

T-cell subsets in spinal fluid of multiple sclerosis patients

CSF T-cells and T-cell subsets were characterized by monoclonal antibodies in 15 untreated multiple sclerosis (MS) patients, 17 immunosuppressed chronic progressive MS patients and 9 patients with other neurological diseases. A negative correlation was found between total cell numbers and T suppressor cell percentages in untreated and treated MS patients. A negative correlation (r = -0.71) was found between intrathecal IgG levels and T suppressor cell percentages in untreated MS patients. In peripheral blood, no correlation between T-cells and T-cell subsets with IgG levels was found. It is discussed that T-cell subsets and intrathecal IgG levels may be indicators of the activity of the inflammatory process in the brains of chronic progressive MS patients.     

Quantitation of T-cell receptor V beta chain expression on lymphocytes from blood, brain, and spinal fluid in patients with multiple sclerosis and other neurological diseases.

Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system in which large numbers of T cells enter the brain and cerebrospinal fluid (CSF). To determine whether these cells represent restricted populations, we studied expression of T-cell receptor V beta chains on paired samples from the central nervous system and blood of patients with MS or other neurological diseases (OND) using a quantitative polymerase chain reaction. The distribution of V beta chain expression in blood was skewed, with a significant preponderance of message from V beta genes 1 through 8 (p = 0.0001). Such skewing was not present in samples from the CSF and brain. Patterns of V beta gene expression were different among paired samples from spinal fluid and blood and were relatively heterogeneous. Blood and CSF samples from a patient with acute meningitis were studied on two separate occasions. The patterns of V beta expression changed over 72 hours in both the blood and the CSF. With one exception, no oligoclonal populations of T cells were observed nor were there disease-specific patterns of V beta gene expression in the blood or CSF. Samples from 2 MS brains and 1 OND brain expressed patterns of V beta genes that were different and less heterogeneous than those in paired blood. In addition, expression of V beta 12 was remarkably increased in the 2 MS brains, suggesting a selective recruitment or expansion of T cells expressing this gene. These data demonstrate that populations of T cells from blood, spinal fluid, and brain differ from one another and can fluctuate during periods of acute inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)     

T-lymphocyte subpopulations in peripheral blood of patients with multiple sclerosis, patients with other neurological diseases and healthy controls

We report our results in profiling peripheral blood lymphocyte subpopulations with monoclonal antibodies in 17 multiple sclerosis (MS) patients, 22 patients with other neurological diseases (OND), and 11 healthy controls, using a blind experiment. Untreated patients with a chronic progressive MS have higher T-helper cell (OKT4+) counts and a higher ratio OKT4+/OKT8+ than other MS patients, OND or healthy controls. Two weeks after the onset of a relapse of MS there is a decreased T-helper and an increased T-suppressor cell percentage. Treatment with ACTH results in a significant increase of helper cells after 4 weeks of therapy. Patients with the lowest helper cell counts and the lowest helper/suppressor ratio show the best clinical improvement by ACTH. High OKT4+ cell percentages make a chronic progressive course of MS more probable.     

Immunoglobulin-producing cells in CSF and blood from patients with multiple sclerosis and other inflammatory neurological diseases enumerated by Protein-A plaque assay

Using the Protein-A plaque assay, numbers of IgG + IgA + IgM producing cells determined in patients with multiple sclerosis (MS) were 0.1–5% in CSF and 0.1–0.7% in peripheral blood; interestingly, 7 of 11 MS patients had IgM producing cells in CSF. In patients with aseptic meningitis (AM), the corresponding values were 0.04–7.5% in CSF and 0.4–2.4% in peripheral blood. There were more Ig producing cells in peripheral blood from patients with AM and MS than in healthy subjects. cocorrelation between numbers of IgG producing cells in CSF and the concentrations of intrathecally produced IgG (CSF IgG index) was registered in patients with AM: the same was true for IgA. The Protein-A plaque method, adopted for 20 × 10³ lymphocytes, makes possible enumeration of Ig-producing cells in CSF and discrimination among cells secreting different Ig classes, thereby being a powerful tool for studying immune reactions in the CNS-CSF compartment.     

A comparison of two neurologic scoring instruments for multiple sclerosis

We examined the degree of association between two neurologic impairment scales, the Extended Disability Status Scale (EDSS) and the Scripps Neurologic Rating Scale (SNRS), with data from a randomized, double-blind, placebo-controlled clinical trial assessing the safety and efficacy of cladribine as treatment for chronic progressive multiple sclerosis (MS). We found that the EDSS and SNRS were not strongly correlated within individual patients, contrary to expectation; moreover, in 9 of the 48 evaluable patients, the directions of their changes from baseline values were not mutually consistent. The scales were differentially sensitive to clinical changes over time, with the EDSS indicating a more abrupt, and the SNRS a more gradual, change in the clinical course of disease. The validity of different impairment scales, and their sensitivity to detect clinical changes, should be formally assessed in future clinical trials using these scales as outcome measures.     

Immunoglobulin M specific for measles in serum and cerebrospinal fluid of patients with multiple sclerosis and other neurological diseases

Summary Serum and cerebrospinal fluid of patients with multiple sclerosis, subacute sclerosing panencephalitis and other neurological diseases have been tested by the indirect fluorescent antibody method for immunoglobulin M specific for measles. Only sera of three patients were positive. This feature is of little statistical importance. Nevertheless the authors emphasize the role of a possible viral infection in the pathogenesis of multiple sclerosis.Presented to the 12th Meeting of the Section of Neuropathology of the Italian Society of Neurology, Massa Marittima, June 5–6, 1976     

Binding properties of cerebrospinal fluid IgG in multiple sclerosis and other neurological diseases

A solid phase radioimmunoassay (RIA) was used to detect antibodies to myelin or myelin basic protein (MBP) in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) or other neurological diseases (OND). When measured at the same IgG concentration, MS samples had higher binding values than OND against myelin, but not against MBP. Using F(ab')2 fragments purified from pools of MS and OND CSF there was no difference in binding to myelin between MS and OND samples. These results indicate that anti-MBP antibodies are nt a feature of MS and binding of CSF IgG to myelin is not due to specific antibody, but is probably the result of non-specific binding to Fc receptors.     

Search for autonomously proliferating spinal fluid lymphocytes in patients with multiple sclerosis

Recently published reports have suggested that multiple sclerosis (MS) may be associated with human retrovirus infection. Indeed, an autonomously proliferating T-cell clone was isolated from the CSF of an MS patient, an observation interpreted as indicating an infection with human T lymphotropic virus I (HTLV I). In view of these findings, we undertook a systematic search for autonomously proliferating cells in the spinal fluids of MS patients and those with other neurologic diseases (OND). In vivo activated blast cells were isolated from the CSF of six MS patients and six OND controls. A total of 442 clones were grown from these cells and assayed for their ability to proliferate independently, without the need for T cell-produced lymphokines. No autonomously proliferating clones were detected. Thus, while our data do not exclude the possibility that HTLV I transformed cells may exist in the CSF of MS patients, they do suggest that such cells are exceptional.