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Journal of neurology, neurosurgery, and psychiatry 04/2013; · 4.87 Impact Factor
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ABSTRACT: Paraneoplastic cerebellar degeneration (PCD) is often associated with Yo antibodies that are directed against human cerebellar degeneration-related protein 2 (CDR2). Such antibodies may also be found in ovarian cancer patients without PCD. We studied if there was an association between Yo antibody production and differences in CDR2 cDNA sequence, mRNA or CDR2 expression in ovarian cancers. We found similar CDR2 cDNA sequence, mRNA and protein levels in primary ovarian cancers, with or without associated Yo antibodies. CDR2 was also present in other cancers, as well as in normal ovary tissue. The results suggest that Yo antibodies are not only related to the expression of CDR2 alone, but also to immune dysregulation.
Cancer Immunology and Immunotherapy 11/2010; 60(2):283-9. · 3.70 Impact Factor
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ABSTRACT: Highly purified IgG administered intravenously (IVIG) is used to treat many neurological diseases.
This review is based on articles identified through a search in PubMed and the authors' knowledge and experience within the field.
The effect of IVIG has been best documented in the treatment of acute and chronic inflammatory demyelinating polyradiculoneuropathy, multifocal motor neuropathy and acute exacerbation of myasthenia gravis. Some smaller studies support explorative IVIG treatment in other neurological diseases such as Lambert-Eaton myasthenic syndrome, paraproteinemic neuropathy, neuropathy caused by vasculitis, inflammatory myopathies and stiff-person syndrome.
IVIG affects the immune system in different ways. Documentation for the effect of such treatment in most neurological diseases remains sparse.
Tidsskrift for den Norske laegeforening 09/2010; 130(17):1717-20.
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ABSTRACT: Mass spectral profiles from cerebrospinal fluid (CSF) are used as input to a novel multivariate approach to select features responsible for the separation of patients with multiple sclerosis (MS) from control groups. Our targeted statistical approach makes it possible to systematically remove features in the spectral fingerprints masking the components expressing the disease pattern. The low molecular weight CSF proteome from 54 patients with MS and a range of other neurological diseases (OND), as well as neurological healthy controls (NHC), is analyzed in replicates using mass spectral profiling. Statistically validated partial least-squares discriminant analysis (PLS-DA) models are created as a first step to separate the groups. Using the group membership as a target, the most discriminatory projection in the multivariate space spanned by the spectral profiles is revealed. From the resulting target-projected component, the spectral regions most significantly contributing to group separation are identified using the nonparametric discriminating variable (DIVA) test together with the so-called selectivity ratio (SR) plot. Our approach is general and can be applied for other diseases and instrumental techniques as well.
Journal of Proteome Research 07/2010; 9(7):3608-20. · 5.11 Impact Factor
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ABSTRACT: We measured the frequency of binding antibody (BAB) and neutralizing antibody (NAB) against interferon-beta (IFN-beta) in sera from 827 patients with relapsing-remitting multiple sclerosis (RRMS) using various IFN-beta medications. Of the 827 patients, 363 (43.9%) had serum BAB after more than 12 months of IFN-beta treatment. Of the 363 BAB-positive sera, we analyzed 137 for BAB using a myxovirus-resistant protein A (MxA) protein induction assay (ELISA) and an MxA messenger RNA (mRNA) induction assay (real-time polymerase chain reaction (PCR)). We obtained similar results for each serum in both NAB assays, indicating a good correlation between transcription and translation of MxA. We tested all 363 sera by real-time PCR, and NAB was present in 70.8% of BAB-positive sera, or 31.1% of the 827 patients with relapsing-remitting multiple sclerosis (RRMS). Real-time PCR offers several advantages for measuring NAB compared with the MxA protein induction enzyme-linked immunosorbent assay and should be used routinely for NAB among patients with MS using IFN-beta treatment.
Journal of neuroimmunology 06/2009; 212(1-2):148-50. · 2.84 Impact Factor
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ABSTRACT: Paraneoplastic neurological syndromes constitute a heterogenous group of diseases, which often cause severe neurological symptoms. Extensive research during the last 20 years has led to identification of new antigenic targets and inclusion of additional clinical conditions into this group of syndromes.
The article is based on a non-systematic search of PubMed and the author's own experience with antibody analysis, treatment of patients and research within the field.
Paraneoplastic neurological syndromes affect less than 1 % of all patients with cancer. The etiology is probably autoimmune, and involves immune responses (cellular and humoral) against antigens shared by tumor cells and normal neurons. Many, but not all patients harbour onconeural antibodies (in serum and spinal fluid), which are highly useful diagnostic markers for a paraneoplastic etiology. The cornerstone of therapy is treatment of the underlying tumor, but additional immunosuppressive therapy is often administered.
Tidsskrift for den Norske laegeforening 04/2009; 129(6):524-8.
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ABSTRACT: The collapsin response mediator protein 5 (CRMP5) antibody is usually associated with paraneoplastic neurological syndrome (PNS) and small-cell lung cancer (SCLC) or thymoma. The objective of this study was to assess the frequency of CRMP5 antibodies in patients with such tumours and to see if the presence of antibodies was associated with prognosis in these cancers. A multi-well adapted immunoprecipitation assay using radiolabelled recombinant CRMP5 protein, produced by coupled in vitro transcription/translation, was used for the detection of CRMP5 antibodies. Sera from 200 patients with SCLC, 73 patients with thymoma and myasthenia gravis (MG) and from 300 healthy blood donors were examined for CRMP5 antibodies. Positive sera were also examined by immunofluorescence and immune blots. The serological results were compared with disease severity of the patients with thymoma or SCLC. CRMP5 antibodies were detected in 10/200 (5%) of the SCLC, 9/73 (12%) of the thymomas and in 2/300 (0.6%) of the healthy controls by immunoprecipitation. The antibodies were less frequently detected by immunofluorescence or immune blots. There was no significant correlation between CRMP5 antibodies and disease severity. CRMP5 antibodies are more than twice as frequent, and the antibody levels are higher in patients with thymoma and MG than in patients with SCLC. The antibodies are correlated to these tumours, but not to disease severity.
Cancer Immunology and Immunotherapy 03/2008; 57(2):227-32. · 3.70 Impact Factor
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ABSTRACT: The etiology of limbic encephalitis (LE) is often autoimmune. Autoimmune LE is often paraneoplastic and should be suspected in patients with subacute confusional states. Subgroups of LE require different treatment, and the prognosis is variable; making the correct diagnosis is therefore essential for a good outcome.
The article is based on the authors' clinical experience with these patients and a review of recent literature retrieved from PubMed with the key words limbic encephalitis, limbic inflammation, paraneoplastic encephalitis, limbic and cancer, ion channel antibodies and viral encephalitis. Two case reports illustrate important clinical points.
Patients with LE constitute a heterogenous group with neuropsychiatric features, seizures and amnesia as the main symptoms. An early diagnosis is essential to limit sequelae. Viral encephalitis and Wernicke-Korsakoff Syndrome are important differential diagnoses. Presence of an onconeural antibody in serum is a specific tumour marker that should be used for screening all patients for malignancy. Not all cases of LE are paraneoplastic; ion channel antibodies can be an important marker for good response to immunosuppressive therapy in this group.
Tidsskrift for den Norske laegeforening 12/2007; 127(23):3077-80.
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ABSTRACT: Mass spectral profiles are influenced by several factors that have no relation to compositional differences between samples: baseline effects, shifts in mass-to-charge ratio (m/z) (synchronization/alignment problem), structured noise (heteroscedasticity), and, differences in signal intensities (normalization problem). Different procedures for pretreatment of whole mass spectral profiles described by almost 50,000 m/z values are investigated in order to find optimal approaches with respect to revealing the information content in the data. In order to quantitatively assess the impact of different procedures for pretreatment of mass spectral profiles, we use factorial designs with the ratio between intergroup and intragroup (replicate) variance as response. We have examined the influence of smoothing, binning, alignment/synchronization, noise pattern, and normalization on data interpretation. Our analysis shows that the spectral profiles have to be corrected for heteroscedastic noise prior to normalization. An nth root transform, where n is a small, positive integer, is used to create a homoscedastic noise structure without destroying the linear correlation structures describing individual components when using whole mass spectral profiles. The choice of n is decided by a simple graphic procedure using replicate information. Log transform is shown to change the heteroscedastic noise structure from being dominant in high-intensity regions, to produce the largest noise in the low-intensity regions. In addition, log transform has a negative effect on the collinearity in the profiles. Factorial designs reveal strong interactions between several of the pretreatment steps, e.g., noise structure and normalization. This underlines the limited usability of looking at the different pretreatment steps in isolation. Binning turns out to be able to substitute smoothing of spectra by, for example, moving average or Savitsky-Golay, while, at the same time, reducing the data point description of the profiles by 1 order of magnitude. Thus, if the sampling density is high, binning seems to be an attractive option for data reduction without the risk of losing information accompanying the integration of profiles into peaks. In the absence of smoothing, binning should be executed prior to alignment. If binning is not performed, the order of pretreatment should be smoothing, alignment, nth root transform, and normalization.
Analytical Chemistry 10/2007; 79(18):7014-26. · 5.86 Impact Factor
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ABSTRACT: There is little information in the literature on the risk of vascular events among patients after ischemic stroke at a young age.
We examined 144 (77%) of 187 long-term survivors of ischemic stroke and compared them with 167 controls. Mean age of the 187 survivors at inclusion was 41.0 years and mean age of the participating patients was 40.8 years.
After a mean duration of observation of 11.8 years, we registered arterial events among 54 patients and 14 controls. Ninety patients with index stroke only had no significant risk factors compared with controls without arterial events. Compared with 54 patients with several arterial events, age, incidence of diabetes mellitus, smoking and family history of coronary disease were significantly lower.
The results from index-stroke-only patients suggest that a subgroup of patients has a benign course, probably without chronic vascular disease.
Cerebrovascular Diseases 02/2007; 24(2-3):277-82. · 2.72 Impact Factor
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ABSTRACT: Paraneoplastic neurological syndromes (PNS) are infrequent disorders that are associated with cancer. The syndromes are highly heterogeneous and often affect several areas of the nervous system. Among the most well-known syndromes are paraneoplastic encephalomyelitis, cerebellar degeneration, sensory neuronopathy, and Lambert-Eaton myastenic syndrome. There are various associated tumors, in particular small cell lung cancer, cancer of the breast and ovary, and thymoma. The onset of neurological symptoms often precedes the cancer diagnosis, and the recognition of a paraneoplastic syndrome should lead to immediate search for cancer. The etiology of the paraneoplastic syndromes is believed to be autoimmune. Antibodies to onconeural antigens, expressed in the tumor of the affected individual and in normal neurons, are found in many of the patients. These antibodies are useful markers for paraneoplastic etiology. The pathogenesis of the PNS is uncertain, but cellular immune responses are thought to be the main effector mechanism. The cornerstone of therapy is the identification and treatment of the underlying malignancy. In some of the disorders, immunosuppressive therapy is of additional benefit. The prognosis of the different PNS varies depending on the level of affection and the degree of neuronal death.
Advances in clinical chemistry 02/2007; 44:143-85. · 3.20 Impact Factor
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ABSTRACT: The presence of circulating antineuronal antibodies has been associated with paraneoplastic neurological syndromes (PNS). Ri antibodies are often associated with lung or breast cancer, but the prevalence of such antibodies in large cancer materials is largely unknown. We used a highly sensitive immunoprecipitation assay to study the level of Ri antibodies in blood samples from 200 patients with small cell lung cancer (SCLC), 253 patients with breast cancer and 557 patients with ovarian cancer. Two hundred blood donors and six Ri positive PNS patients served as controls. The recombinant antigen used in the immunoprecipitation assay was radiolabeled by a coupled in vitro transcription and translation (ITT) technique, enabling low levels of antibodies to be detected. None of the blood donors contained Ri antibodies, whereas all of the sera from the PNS patients were positive. Ri antibodies were present in 4.5% of the patients with SCLC, 0.8% of the patients with breast cancer and in 0.2% of the patients with ovarian cancer. Retesting of the Ri positive samples with immunofluorescense and immune blot showed that the immunoprecipitation technique was more sensitive than the other immune assays. Ri antibodies were not associated with PNS in the patients with breast or ovarian cancer. Neurological data were not available for the SCLC patients, but in these, Ri antibodies were not associated with survival.
Cancer Immunology and Immunotherapy 11/2006; 55(10):1280-4. · 3.70 Impact Factor
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ABSTRACT: Antibodies to proteasome have been detected in several autoimmune diseases, including multiple sclerosis. We have investigated the presence of such antibodies in patients with paraneoplastic neurological syndromes, by Western blotting and immunohistochemistry. Antibodies to 20S proteasome were detected in the majority of patients with paraneoplastic cerebellar degeneration (PCD), but in only one of nine sera from patients with paraneoplastic encephalomyelitis/sensory neuronopathy (PEM/SN), and were not found in cancer patients in general. The results suggest that the immune responses in PCD differ from those of PEM/SN, whereas the functional significance of proteasome antibodies in PCD is yet to be determined.
Journal of Neuroimmunology 09/2005; 165(1-2):172-8. · 2.96 Impact Factor
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ABSTRACT: Receptors for the Fc domain of IgG (Fc gammaR) play a critical role in linking cellular and humoral immunity. The various Fc gammaR genotypes may contribute to differences in infectious and immune-related diseases in various ethnic populations. The Samis are the aboriginal inhabitants of Norway and Fennoscandinavia and differ ethnically from the Norwegians. The distribution of various immune-related diseases has been reported to differ between Sami and Norwegians. This is the first study to evaluate the distribution of Fc gammaR polymorphisms in a Sami population. Two hundred Samis were genotyped for polymorphisms in the Fc gammaRIIA, Fc gammaRIIIA and Fc gammaRIIIB genes. The genotype and allele frequencies were compared with those of 272 healthy Norwegians. The Sami and Norwegian Fc gammaRIIA, Fc gammaRIIIA and Fc gammaRIIIB genotypes differed significantly. The Samis had higher frequencies of the Fc gammaRIIa-H/H131, Fc gammaRIIIa-F/F158 and Fc gammaRIIIb-NA1/NA1 genotypes. The Fc gammaR genotypes were non-randomly distributed in both populations. These findings may be important for the prevalence of autoimmune and infectious diseases in the two populations.
Immunology 08/2005; 115(3):416-21. · 3.32 Impact Factor
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Nina M van Sorge,
W-Ludo van der Pol,
Marc D Jansen,
Karin P W Geleijns,
Sandra Kalmijn,
Richard A C Hughes,
Jeremy H Rees,
Jane Pritchard, Christian A Vedeler,
Kjell-Morten Myhr,
Chris Shaw,
Ivo N van Schaik,
John H J Wokke,
Pieter A van Doorn,
Bart C Jacobs,
Jan G J van de Winkel,
Leonard H van den Berg
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ABSTRACT: Macrophages and ganglioside-specific IgG are involved in the pathogenesis of Guillain-Barre syndrome (GBS). Leukocyte IgG receptors (Fc gammaR) confer potent cellular effector functions to the specificity of IgG. The efficacy of IgG-mediated cellular inflammatory responses is determined by functional polymorphisms of three Fc gammaR subclasses (Fc gammaRIIa: H131/R131; Fc gammaRIIIa: V158/F158; Fc gammaRIIIb: NA1/NA2). Fc gammaR genotype distributions were determined in a Dutch, and British cohort of GBS patients and controls. In addition, a meta-analysis incorporating all previously published data, encompassing a total of 345 GBS patients and 714 healthy controls, was performed. Results suggest that Fc gammaRIII genotypes may represent mild disease-modifying factors in GBS.
Journal of Neuroimmunology 06/2005; 162(1-2):157-64. · 2.96 Impact Factor
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ABSTRACT: Miller-Fisher syndrome is characterised by the clinical triad of ophthalmoplegia, ataxia and areflexia and is considered a variant form of Guillain-Barré syndrome. In western countries the incidence is reported to be approximately 1-5% that of Guillain-Barré syndrome. Approximately 90% of patients have antibodies against the ganglioside GQ1b, which is of diagnostic and pathogenic importance.
We present two patients with Miller-Fisher syndrome and describe clinical features and possible mechanisms of GQ1b antibodies.
Both patients presented with the classical triad of symptoms and GQ1b antibodies after upper respiratory tract infections. One of the patients had a more severe form with additional bulbar signs and was treated with plasma exchange. Both made almost complete recoveries within a few months.
Tidsskrift for den Norske laegeforening 06/2005; 125(10):1327-8.
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ABSTRACT: Inflammation is important in the pathogenesis of atherosclerosis. Polymorphisms of Fc receptors for IgG (FcgammaR) are associated with modifying effects of several infectious and autoimmune diseases. We have assessed the relationship between polymorphisms in three different FcgammaR genes and coronary artery disease (CAD).
We genotyped for the FcgammaRIIA-R/H131, the FcgammaRIIIB-Na1/Na2, and the FcgammaRIIIA-F/V158 polymorphisms in 882 patients undergoing diagnostic coronary angiography. Significant CAD was defined as >/=50% lumen diameter stenosis in at least one coronary artery. In the analysis, no association was found between the FcgammaRIIA and FcgammaRIIIB genotypes and CAD, whereas the FcgammaRIIIA genotype was strongly related. Compared to those being heterozygous, or homozygous for the F allele, patients homozygous for the V allele had significantly reduced risk: OR, 0.53; (CI, 0.32-0.90). Additional adjustment for classical risk factors and sedimentation rate did not affect the results. The V/V genotype was also inversely related to the extent of CAD defined as no CAD, single, double or triple vessel disease (P trend=0.002).
Our data provide evidence for an association between FcgammaRIIIA allelic variants and coronary atherosclerosis. Genetic variation in this IgG-receptor may influence the clearance of antibodies by monocyte-derived macrophages involved in the pathogenesis of CAD.
Atherosclerosis 06/2005; 180(2):277-82. · 3.79 Impact Factor
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ABSTRACT: Receptors for the Fc domain of IgG (FcγR) play a critical role in linking cellular and humoral immunity. The various FcγR genotypes may contribute to differences in infectious and immune-related diseases in various ethnic populations. The Samis are the aboriginal inhabitants of Norway and Fennoscandinavia and differ ethnically from the Norwegians. The distribution of various immune-related diseases has been reported to differ between Sami and Norwegians. This is the first study to evaluate the distribution of FcγR polymorphisms in a Sami population. Two hundred Samis were genotyped for polymorphisms in the FcγRIIA, FcγRIIIA and FcγRIIIB genes. The genotype and allele frequencies were compared with those of 272 healthy Norwegians. The Sami and Norwegian FcγRIIA, FcγRIIIA and FcγRIIIB genotypes differed significantly. The Samis had higher frequencies of the FcγRIIa-H/H131, FcγRIIIa-F/F158 and FcγRIIIb-NA1/NA1 genotypes. The FcγR genotypes were non-randomly distributed in both populations. These findings may be important for the prevalence of autoimmune and infectious diseases in the two populations.
Immunology 04/2005; 115(3):416 - 421. · 3.32 Impact Factor
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ABSTRACT: Patients with paraneoplastic neurological syndromes often produce intrathecal antibodies. We have employed isoelectric focusing and peroxidase-labeled anti-IgG or 35S-labeled Hu or Yo antigens to identify oligoclonal bands (OCB) representing either total IgG or Hu or Yo antibodies in serum and CSF of patients with paraneoplastic encephalomyelitis (PEM) or paraneoplastic cerebellar degeneration (PCD). OCBs representing paraneoplastic antibodies were found in all CSF, but in only three sera. Yo antibodies represented the majority of IgG bands in PCD-CSF, which may reflect a limited immune response, whereas in PEM/SN, there were numerous additonal IgG bands of unknown specificity, indicating a broader immune response in these patients.
Journal of Neuroimmunology 11/2004; 155(1-2):150-4. · 2.96 Impact Factor
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ABSTRACT: The extent and pattern of demyelination in the cerebral cortex was determined in 78 tissue blocks from the brains of 20 multiple sclerosis (MS) patients and 28 tissue blocks from 7 patients without neurological disease. Tissue blocks from 4 predetermined areas (cingulate gyrus, frontal, parietal, and temporal lobe) were studied, irrespective of macroscopically evident MS plaques. All tissue blocks contained cerebral cortex and periventricular and/or subcortical white matter. One hundred and nine demyelinating lesions were detected in the cerebral cortex, of which 92 (84.4%) were purely intracortical and 17 (15.6%) were lesions extending through both white and gray matter areas. In 5 of the 20 MS brains, subpial demyelination was extensive in the 4 widely spaced cortical areas studied, thus considered to represent a general cortical subpial demyelination. The percentage of demyelinated area was significantly higher in the cerebral cortex (mean 26.5%, median 14.1%) than in white matter (mean 6.5%, median 0%) (p = 0.001). Both gray and white matter demyelination was more prominent in the cingulate gyrus than in the other areas examined (p < 0.05). These results indicate that the cerebral cortex is likely to be a predilection site for MS lesions and identify general cortical subpial demyelination as a distinct pattern occurring in a significant subpopulation of MS patients.
Journal of Neuropathology and Experimental Neurology 07/2003; 62(7):723-32. · 4.26 Impact Factor
