Biomedical subjects

F Sellebjerg

Publications and source records attributed to F Sellebjerg.

46 records · Page 3Linked to original sources

PubMed1998

Costimulatory CD80 (B7-1) and CD86 (B7-2) on cerebrospinal fluid cells in multiple sclerosis.

The costimulatory CD80 and CD86 molecules were measured by flow cytometry on cerebrospinal fluid (CSF) and blood lymphocytes from patients with possible first attacks of multiple sclerosis (MS, n = 25), clinically definite MS (n = 16), and noninflammatory neurological disease control subjects (n = 30). In patients with demyelinating diseases more CSF B cells expressed CD80 than in control subjects whereas the expression of CD86 by T cells in CSF was low in patients with demyelinating disease and highly variable in the control subjects. In patients with possible first attacks of MS the expression pattern of CD80 and CD86 differed significantly between patients with or without intrathecal synthesis of IgG. Increased expression of the CD80 molecule on CSF B cells may be of importance in the pathogenesis of MS. In contrast, CSF T cell expression of CD86 may be associated with protection from MS.

Acute Disease↗

PubMed1998

Intrathecal synthesis of free immunoglobulin light chains in multiple sclerosis.

OBJECTIVE: The detection of oligoclonal immunoglobulin free light chains (FLC) in the diagnosis of multiple sclerosis (MS) was compared to IgG isoelectric focusing. MATERIAL AND METHODS: Cerebrospinal fluid and serum samples from 69 patients with possible first attacks of MS, 50 patients with clinically definite MS (CDMS), and 118 patients with other neurological diseases (OND) were analyzed. IgG and FLC oligoclonal bands were detected by isoelectric focusing and immunoperoxidase staining. RESULTS: Intrathecal synthesis of IgG, kappa FLC, and lambda FLC oligoclonal bands, respectively, was seen in 92%, 92%, and 86% of MS patients; in 61%, 62%, and 64% of patients with possible first attacks of MS; and in 3%, 3%, and 8% of the patients with OND. In control patients without IgG synthesis intrathecal lambda FLC synthesis was more common than kappa FLC synthesis (P=0.03). CONCLUSION: Kappa FLC detection proved as useful as IgG analysis for the laboratory diagnosis of MS whereas the presence of intrathecal lambda FLC synthesis was less specific.

Cerebrospinal Fluid↗

PubMed1998

MBP, anti-MBP and anti-PLP antibodies, and intrathecal complement activation in multiple sclerosis.

Intrathecal immunoglobulin synthesis and activation of the complement cascade occurs in patients with multiple sclerosis (MS). The present study aimed at further studying the relation between intrathecal immunoglobulin synthesis and complement activation. We compared total intrathecal synthesis of IgA, IgG, and IgM, the number of cells secreting anti-myelin basic protein (MBP) and anti-proteolipid protein (PLP) antibodies of the IgG isotype and intrathecal activation of the complement cascade in patients with possible onset symptoms of MS (n = 18) or clinically definite MS (n = 30). Early activation of the complement cascade correlated with intrathecal synthesis of IgM. Intrathecal IgG, IgA and IgM synthesis also correlated weakly with the presence of cells secreting anti-MBP or anti-PLP autoantibodies. Full activation of the complement cascade did not correlate with any measures of intrathecal antibody synthesis. These findings suggest a complex relation between different immunoglobulin isotypes and complement activation which may have similarly complex roles in the pathogenesis of MS.

Acute Disease↗

PubMed1998

Cerebrospinal fluid measures of disease activity in patients with multiple sclerosis.

The potential of magnetic resonance imaging to serve as a surrogate marker of disease activity in patients with multiple sclerosis (MS) is increasingly recognised. In contrast, the use of cerebrospinal fluid analysis has received less attention. We analysed the correlation between clinical data and cerebrospinal fluid parameters in 75 patients with acute optic neuritis (ON) as a possible first symptom of MS, as a symptom of clinically definite MS, and in patients with an attack of MS other than ON. The samples were obtained within 30 days from the onset of an exacerbation. The concentration of myelin basic protein (MBP) in cerebrospinal fluid was significantly correlated with the visual acuity in patients with ON and the Kurtzke EDSS score in patients with MS. The concentration of MBP in CSF also correlated positively with the CSF leukocyte count, intrathecal IgG synthesis, and the CSF-serum albumin concentration quotient. The concentration of MBP in CSF correlated negatively with intrathecal IgA synthesis. The results support the use of the concentration of MBP in CSF as a surrogate marker of disease activity during acute exacerbations of MS; the data also link the presence of MBP in CSF to neuroimmunological parameters.

Adolescent↗

PubMed1998

Double-blind, randomized, placebo-controlled study of oral, high-dose methylprednisolone in attacks of MS.

OBJECTIVE: There is only limited evidence from adequately controlled clinical trials to support high-dose methylprednisolone therapy for attacks of multiple sclerosis (MS) and none supporting oral administration. We assessed the effect of oral high-dose methylprednisolone therapy in attacks of MS. METHODS: Twenty-five patients with an attack of MS lasting less than 4 weeks were randomized to placebo treatment. Twenty-six patients received oral methylprednisolone (500 mg once a day for 5 days with a 10-day tapering period). The patients received scores on the Scripps Neurological Rating Scale (NRS) and Kurtzke Expanded Disability Status Scale. The symptoms were scored on a visual analog scale (VAS) before treatment and after 1, 3, and 8 weeks of treatment. Primary efficacy measures were NRS and VAS scores in the first 3 weeks and changes in NRS score and answers to an efficacy questionnaire administered after 8 weeks of treatment. RESULTS: Changes in NRS scores among methylprednisolone- and placebo-treated patients differed significantly in the first 3 weeks and after 8 weeks (p = 0.005 and p = 0.0007). VAS scores the first 3 weeks and treatment efficacy after 8 weeks also favored a beneficial effect of methylprednisolone treatment (p = 0.02 and p = 0.05). After 1, 3, and 8 weeks, 4%, 24%, and 32% in the placebo group and 31%, 54%, and 65% in the methylprednisolone group had improved one point on the Expanded Disability Status Scale score (all p < 0.05). No serious adverse events were seen. CONCLUSION: Oral high-dose methylprednisolone is recommended for managing attacks of MS.

Administration, Oral↗

PubMed1996

Interleukin-8 in cerebrospinal fluid from patients with septic and aseptic meningitis.

Using a monoclonal antibody enzyme immunoassay, the concentration of interleukin-8 (IL-8) in cerebrospinal fluid (CSF) from 52 patients suspected of having meningitis was studied. The CSF IL-8 concentration was significantly higher in septic meningitis of known and unknown etiology than in aseptic meningitis and significantly higher in aseptic meningitis than in patients without meningitis. The CSF levels of IL-8 correlated with the levels of tumor necrosis factor-alpha, leukocyte count, neutrophil count, protein level, CSF/blood glucose ratio, and the number of days patients were hospitalized. The IL-8 values used to distinguish septic from aseptic meningitis, at a cut-off point of 3.00 micrograms/l, showed a sensitivity of 81%, a specificity of 92%, and a positive predictive value of 96%. The results suggest that determining IL-8 levels may be useful in the differential diagnosis of meningitis.

Adolescent↗

PubMed1996

Qualitative assessment of intrathecal IgG synthesis by isoelectric focusing and immunodetection: interlaboratory reproducibility and interobserver agreement.

Detection of intrathecal IgG synthesis is important in patients with suspected multiple sclerosis (MS). The recommended method for the detection of intrathecal synthesis of IgG is isoelectric focusing and immunodetection of oligoclonal bands. Recently "The Committee for European Concerted Action for Multiple Sclerosis" has recommended that the results of isoelectric focusing for the detection of intrathecal synthesis of oligoclonal bands should not only be stated as positive or negative for intrathecal synthesis; instead, the laboratory should provide a detailed description of the IgG pattern in both cerebrospinal fluid (CSF) and serum together with a conclusion concerning the presence of intrathecal synthesis. We studied the interlaboratory reproducibility and interobserver agreement of isoelectric focusing, and the recommended classification system for the assessment of intrathecal IgG synthesis, in two separate patient groups employing kappa statistics. We found a high degree of interlaboratory reproducibility (133 patients; kappa = 0.95 +/- 0.05) and interobserver agreement (356 patients; kappa = 0.97 +/- 0.04) when the presence or absence of intrathecal IgG synthesis was assessed. The agreement was less pronounced, although still fully satisfactory, when the results were classified according to the detailed system by two laboratories (133 patients; kappa = 0.86 +/- 0.08) and two observers (356 patients; kappa = 0.88 +/- 0.08). Two specific problems in the interpretation of isoelectric focusing patterns were identified: one related to the discrimination of a pattern with several closely spaced bands which may represent a monoclonal protein; the other related to determining whether systemic band synthesis was present. We conclude that isoelectric focusing and immunodetection is a very reproducible technique for the detection of intrathecal IgG synthesis. Well defined criteria and extensive standardization may, however, be necessary when more elaborate classification systems are employed.

Humans↗

PubMed1995

Acute optic neuritis: myelin basic protein and proteolipid protein antibodies, affinity, and the HLA system.

Anti-myelin basic protein, anti-proteolipid protein, and anti-myelin basic protein peptide (amino acid residues 1-20, 63-88, and 89-101) antibody-secreting cells were studied in 20 patients with idiopathic optic neuritis, 20 with optic neuritis as part of multiple sclerosis, and 20 neurological control subjects. Antibody-secreting cells were enumerated with an immunospot assay; the relative binding affinity of the antibodies was estimated by elution with thiocyanate. Patients with optic neuritis had more anti-myelin basic protein and anti-proteolipid protein antibodies than did control subjects (both p < 0.05); there was no difference between idiopathic optic neuritis and optic neuritis as a symptom of multiple sclerosis. Presence of the multiple sclerosis-associated DRB1*1501 gene was not associated with preferential synthesis of high-affinity antibodies reactive with a single myelin basic protein peptide or with preferential synthesis of either anti-myelin basic protein or anti-proteolipid protein antibodies. The results demonstrate a potential for intrathecal synthesis of both anti-myelin basic protein and anti-proteolipid protein antibodies of high apparent affinity in patients with optic neuritis.

Adolescent↗

PubMed1994

Peptide specificity of anti-myelin basic protein antibodies in patients with acute optic neuritis and the HLA system.

Multiple sclerosis (MS) may be an autoimmune disease, partially caused by autoreactivity to myelin basic protein (MBP) and other central nervous system proteins. Acute optic neuritis (ON) is a frequent first symptom of MS. The role of the HLA system in anti-MBP antibody production in ON was investigated employing a restriction fragment length polymorphism system for genomic HLA-DQ and -DR typing and an immunospot assay for the detection of individual cells secreting antibodies to three different synthetic MBP peptides. Thirty-two out of 40 patients (80%) with ON had cells in cerebrospinal fluid secreting anti-MBP peptide antibodies while this occurred in 10/19 patients with other neurological diseases (53%; mainly in patients with inflammatory diseases in the central nervous system). This difference was statistically significant (P = 0.03). None of the three examined peptides were immunodominant in any patient group. It was found, however, that presence of HLA DR15, which is associated with MS, may be associated further with predominant production of antibodies to the MBP amino acids 63-88 in patients with ON (P = 0.002, corrected for multiple comparisons).

Adult↗

PubMed1993

[IGG index or oligoclonal bands in the diagnosis of disseminated sclerosis].

Intrathecal synthesis of IgG was measured in 136 patients using agarose isoelectric focusing followed by immunoperoxidase staining for the detection of oligoclonal bands, and separate measurement of the IgG-index by immune electrophoresis. Oligoclonal bands were detected in 10/52 patients with other neurological diseases (OND). Five of these patients had possible multiple sclerosis (MS), and five had infections of the central nervous system. Oligoclonal bands were detected significantly more often in patients with clinically definite MS (24/26 patients (92%): p < 10(-9)) and in patients with acute optic neuritis, which is often an early manifestation of MS (34/58 patients (56%): p = 0.00005). An elevated IgG-index was detected in 15/25 MS-patients (60%), and in 13/56 patients with optic neuritis (20%). We conclude that isoelectric focusing is a valuable method for the detection of intrathecal production of IgG, and, especially in optic neuritis, has a higher sensitivity than the IgG-index. The method is recommended in the routine diagnosis of MS.

Adolescent↗