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Biomedical subjects

S Fredrikson

Publications and source records attributed to S Fredrikson.

At least 109 records · Page 6Linked to original sources
PubMed1992

Conjugal multiple sclerosis: immunogenetic characterization and analysis of T- and B-cell reactivity to myelin proteins.

We describe two families with conjugal multiple sclerosis. Onset of symptoms in the husbands occurred 11 and 17 years after onset of relapsing/remitting symptoms in their wives. There were no similarities regarding clinical manifestations of MS within each family. Evaluation of T-cell repertoire by enumeration of cells secreting interferon-gamma in response to proteolipid protein (PLP), myelin basic protein (MBP), and to various synthetic MBP peptides revealed similar patterns of T-cell reactivity within the families both in MS-affected parents and unaffected children. Genomic HLA-DR-DQ typing showed that T-cell reactivity was independent of HLA class II phenotype. Analysis of B-cell responses in blood showed low numbers of cells secreting IgG, IgA, or IgM antibodies against MBP, PLP, myelin-associated glycoprotein, and myelin-oligodendrocyte glycoprotein both in MS-affected and unaffected family members. In conclusion, our study of two families with conjugal MS has shown a dominant T-cell response against the same MBP peptide within the family both in MS-affected parents and unaffected children, and this T-cell response seems to be independent of the HLA class II phenotypes of the family members.

Adult↗
PubMed1991

Autoreactive T and B cells responding to myelin proteolipid protein in multiple sclerosis and controls.

The pathogenesis of multiple sclerosis (MS) could involve an autoimmune response to proteolipid protein (PLP). Immunization of experimental animals with this major myelin protein can lead to experimental allergic encephalomyelitis. To identify a possible role of PLP as target antigen in MS, we evaluated T cell immunity to PLP in blood and cerebrospinal fluid (CSF) from patients with MS and controls by counting cells which in response to PLP in short-term cultures secreted interferon-gamma. The PLP-specific B cell response was analyzed by counting cells secreting anti-PLP antibodies. PLP-reactive T cells were detected in blood of most MS patients (mean value 1 per 20,408 mononuclear cells), and at 41-fold higher numbers in CSF (mean 1 per 500 CSF cells). Anti-PLP IgG antibody-secreting cells were detected in blood from most MS patients (mean 1 per 30,303 cells), but such cells were 49-fold more frequent in CSF (mean 1 per 625 cells). PLP-reactive T and B cells were also detected in blood and CSF from control patients, but at much lower numbers. A strong and persistent autoimmune response to PLP as well as to other myelin proteins, enriched in CSF, is proposed to be pathogenetically important in MS.

Adolescent↗
PubMed1991

Cells producing antibodies specific for myelin basic protein region 70-89 are predominant in cerebrospinal fluid from patients with multiple sclerosis.

Cells secreting antibodies against guinea pig myelin and synthetic myelin basic protein (MBP) peptides were evaluated in cerebrospinal fluid (CSF) and blood from patients with multiple sclerosis (MS) and a variety of other neurological diseases (OND). The peptides used, reproducing amino acid sequences 1-20, 70-89, 108-126, or 157-166 of MBP, were selected on the basis of their hydrophilic and encephalitogenic properties. Low numbers of cells secreting IgG antibodies against myelin or each of the MBP peptides (about 1 per 50,000) were detected in peripheral blood, with no difference between MS and OND. In CSF, cells secreting IgG antibodies to MBP 70-89 were more frequently (p = 0.007) detected in patients with MS (1/380 IgG-secreting cells on average) than in patients with OND (1/2083 IgG-secreting cells on average). The frequencies of cells secreting antibodies against myelin or the three other MBP peptides were similar in MS and OND. Thus, evaluation of B cell immunity at the cellular level indicates that MBP 70-89 is an immunodominant B cell epitope in MS. It is not clear whether this intrathecal anti-MBP 70-89 IgG antibody response has any pathogenetic relevance in MS or is the result of myelin breakdown.

Adult↗
PubMed1991

CD5+ B cells and CD4-8-T cells in neuroimmunological diseases.

Using 2- and 3-colour FACS analysis we found increased levels of fetal-type CD5+ B cells and CD4-8- T cells in cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) and aseptic meningitis (AM) compared to control probands with muscular tension headache (TH). Similar differences were found for CD5+ B cells in peripheral blood, but at lower levels. CD4-8- T cells in blood exceeded those in CSF in all patient groups, with the exception of relapsing remitting MS, revealing the highest values in AM. There was a positive correlation between CD4-8- T cells and T cell receptor (TCR) gamma delta bearing T cells in blood and CSF. The double-negative T cells exceeded the TCR gamma delta T cells by about 1%. A positive correlation between CD5+ B cells and CD4-8- T cell level in CSF was found in MS and AM, but not in TH, nor in blood of any patient group. HLA-DR expression was lower in CD5+ B cells than in CD5- B cells. We conclude that fetal-type lymphocytes are enriched in CSF compartment of patients with inflammatory diseases of the central nervous system, irrespective of autoimmune mechanisms involved, but the function of CD5+ B cells is mainly to produce the autoantibodies.

Adolescent↗
PubMed1991

Interleukin-6 is elevated in plasma in multiple sclerosis.

Levels of interleukin-6 (IL-6)--a cytokine which induces immunoglobulin production of activated B cells--were measured in cerebrospinal fluid (CSF) and plasma of patients with multiple sclerosis (MS), acute meningo-encephalitis (AM) and muscular tension headache (TH). MS patients had in repeated samples higher levels of IL-6 in plasma compared to patients with AM and TH. IL-6 concentrations in MS plasma were about 17 times higher than MS CSF, while in AM 20-fold higher levels were found in CSF compared to plasma during the acute stage. IL-6 in AM CSF decreased rapidly during clinical recovery. No correlation was found between IL-6 in MS patients' plasma or CSF and disease activity. The functional significance of elevated IL-6 concentrations in MS plasma is unknown, although the findings support the hypothesis of a systemic B cell response in MS.

Acute Disease↗
PubMed1991

Cord blood contains cells secreting antibodies to nervous system components.

Umbilical cord blood of newborns and peripheral blood of healthy adults were investigated by an immunospot assay for cells secreting IgG, IgA and IgM antibodies against myelin basic protein (MBP), proteolipid protein (PLP), myelin-associated glycoprotein (MAG) and myelin oligodendrocyte glycoprotein (MOG) which represent putative antigens for an autoimmune attack in multiple sclerosis (MS) and against acetylcholine receptor (AChR) which is considered an important autoantigen in myasthenia gravis. Cells secreting antibodies against one or more of these autoantigens were detected in 18 out of 24 newborns, and in eight out of 20 adults. Eight of the cord blood samples contained cells secreting antibodies of IgG, IgA and/or IgM isotypes to one antigen, five to two antigens, two to three antigens, two to four antigens, and one to five antigens. Most prominent were anti-MBP IgG antibody secreting cells which were detected in 13 newborns at a mean number of 1/20,000 cord blood cells, and in six adults at a mean number of 1/10(5) peripheral blood cells. Anti-AChR IgG antibody secreting cells were detected in four out of 12 newborns versus four out of 14 peripheral blood specimens, at mean values of 1/10(5) cells in both instances. Cells secreting autoantibodies of IgA and IgM isotypes were less frequent both in cord blood and peripheral blood. The occurrence of nervous tissue autoantibody secreting cells in newborns must be related to a possible primary role of such autoantibodies in MS and myasthenia gravis.

Adult↗
PubMed1991

Immunoglobulin producing cells in bone marrow and blood of patients with multiple sclerosis and controls.

Multiple sclerosis (MS) is characterised by intrathecal synthesis of IgG, less frequently of IgA and IgM. Local production of antibodies to myelin basic protein (MBP) and other myelin components has also been reported, and autoimmune pathogenesis has been postulated. Whether MS is accompanied by a systemic B cell response is less clear. To elucidate this question, we examined bone marrow and peripheral blood from patients with MS and controls for cells secreting IgG, IgA and IgM, as well as anti-MBP antibodies of these three isotypes. Patients with MS without any signs of concurrent infections had higher numbers of IgG + IgA + IgM secreting cells both in bone marrow and peripheral blood compared with healthy controls. The same abnormalities were observed in patients with other inflammatory neurological diseases (OIND). When analysing individual isotypes, patients with MS and OIND had higher numbers of IgA secreting cells both in bone marrow and blood compared with healthy controls. Only one of 13 MS patients examined had anti-MBP antibody secreting cells in bone marrow and blood. The systemic B cell response registered in MS is also present in other inflammatory neurological diseases and its specificity and possible role in the pathogenesis of MS remains unknown.

Adult↗
PubMed1990

CSF immune variables in patients with narcolepsy.

Cerebrospinal fluid (CSF) and serum from 15 patients with narcolepsy were examined regarding presence of oligoclonal bands on isoelectric focusing, IgG index elevation as indicator of intrathecal IgG production and CSF/serum albumin ratios. Two of 15 patients (13%) showed oligoclonal IgG bands in CSF, one of whom had increased IgG index. Slight disturbance of blood-brain-barrier function as reflected by elevated CSF/serum albumin ratios was present in 4 other patients. The frequency of oligoclonal IgG bands in CSF from patients with narcolepsy is within the range of what is found in other neurological, non-inflammatory diseases. These findings do not support the hypothesis of an immune-mediated pathogenesis of narcolepsy.

Adolescent↗
PubMed1989

Mononuclear cell types in cerebrospinal fluid and blood of patients with multiple sclerosis. Quantitation by immunoenzyme microassay with panel of monoclonal antibodies.

Phenotypic distribution of mononuclear cells in cerebrospinal fluid (CSF) and peripheral blood from patients with multiple sclerosis (MS) and, for reference, patients with acute aseptic meningoencephalitis (AM), and in blood only from healthy controls, was studied with an immunoenzymatic microassay enabling analysis even in the presence of a normal CSF cell count. In MS, increased CD5+ (pan-T) cell proportion in CSF compared with blood was not reflected by changes of CD4+ or CD8+ cells, while in AM, an increase of CD4+ cells was registered. Therefore, a population of CD5+, CD4-, and CD8- cells may be anticipated to exist in CSF of patients with MS. Numbers of OKB7+, OKM1+, or HLA-DR+ cells did not distinguish between MS and AM. Proliferating cells expressing transferrin receptors (OKT9+ cells) were generally few or absent in CSF and not useful as a marker of disease activity in either MS or AM.

Acute Disease↗
PubMed1989

Total, anti-viral, and anti-myelin IgG subclass reactivity in inflammatory diseases of the central nervous system.

Total IgG subclass levels, anti-viral, anti-myelin basic protein (anti-MBP), and anti-ganglioside 1 (anti-GM1) IgG subclass levels were measured in 6 patients with herpes simplex virus encephalitis (HSVE), 16 with borreliosis, 8 with other bacterial infections, 12 with multiple sclerosis (MS), 13 with subacute sclerosing panencephalitis (SSPE), 5 with glioblastoma and 12 controls. Total IgG1 levels were elevated in cerebrospinal fluid (CSF) from all patient groups (but not in the controls), IgG2 in bacterial infections, IgG3 in HSVE and borreliosis and IgG4 in some SSPE patients. The anti-viral (anti-measles, varicella zoster virus and rubella) IgG antibodies in MS were restricted to IgG1, anti-measles IgG to IgG1 and sometimes IgG4 in SSPE, anti-borrelia IgG to IgG1, IgG2 and IgG3. In contrast to anti-viral antibodies, anti-MBP and GM1 antibodies belonged to IgG1, IgG3 or IgG4 in MS. The nature of the immunological activation appears to be reflected in the subclass patterns elicited in the central nervous system. Different IgG subclass patterns in infectious diseases and MS suggest a difference between antigen-specific and non-specific B-cell activation.

Antibodies↗
PubMed1989

Bone marrow cells in patients with multiple sclerosis.

Bone marrow cells from patients with multiple sclerosis (MS) were studied regarding proliferative capacity with and without mitogenic stimulation, immunohistochemical characterization of cellular phenotypes with monoclonal antibodies and morphology and compared to bone marrow cells from healthy individuals undergoing elective orthopaedic surgery. MS patients' bone marrow mononuclear cells (BM-MNC) showed higher spontaneous proliferation both in comparison with BM-MNC from controls and peripheral blood mononuclear cells (PBL) from MS patients. Phytohaemagglutinin (PHA) response was higher in MS BM-MNC than BM-MNC from controls. MS patients' BM-MNC proliferated more on interleukin-2 (IL-2) stimulation than their corresponding PBL. There was no significant difference in proliferative response of PBL between MS patients and controls. Higher levels of undifferentiated or activated cells, as measured by OKT10, were found in peripheral blood of patients with MS. Seven of 11 MS patients showed morphological signs of activation in their bone marrow. The results indicate a role for immune reactions in bone marrow in the pathogenesis of multiple sclerosis, a disease with symptoms and signs strictly confined to the central nervous system.

Adult↗
PubMed1989

Primarily chronic progressive and relapsing/remitting multiple sclerosis: two immunogenetically distinct disease entities.

HLA class II gene polymorphism was investigated in 100 patients with clinically definite multiple sclerosis (MS) by restriction fragment length polymorphism analysis of Taq I-digested DNA using DRB, DQA, and DQB cDNA probes. Twenty-six patients had primarily chronic progressive MS and 74 had relapsing/remitting MS. The latter group included patients with a secondary progressive evolution of symptoms. Both clinical forms of MS were found to be associated with the DRw15,DQw6 haplotype. In addition, primarily chronic progressive MS was positively associated with the DQB1 restriction fragment pattern seen in DR4,DQw8, DR7,DQw9, and DRw8, DQw4 haplotypes, as well as negatively associated with the Taq I DQB1 allelic pattern corresponding to the serological specificity DQw7. Relapsing/remitting MS was positively associated with the DQB1 allelic pattern observed in the DRw17,DQw2 haplotype. These three DQB1 alleles are in strong negative linkage disequilibria with DRw15. The two susceptibility markers of each clinical form of MS act additively in determining the genetic susceptibility, as the relative risks for individuals carrying both markers roughly equal the sum of respective risks. Different alleles of the DQB1 locus defined by restriction fragment length polymorphisms contribute to susceptibility and resistance to primarily chronic progressive MS as well as to susceptibility to relapsing/remitting MS. The observed immunogenetic heterogeneity between the different clinical forms of MS favors the hypothesis that primarily chronic progressive MS and relapsing/remitting MS are two distinct disease entities.

Alleles↗
PubMed1989

Retrovirus in multiple sclerosis.

Presence of cytopathic effect and enzyme reverse transcriptase in cultures of peripheral blood mononuclear cells is described in 2 of 15 patients with multiple sclerosis and none of healthy controls. These findings might indicate: the presence of a new human retrovirus in these individuals, despite the low detection rate, and the shortcomings inherent in methodology used for detection of known human retroviruses in the study of new groups of diseases, such as those with possible autoimmune background.

Adult↗