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Tom W J Huizinga

Publications and source records attributed to Tom W J Huizinga.

77 records · Page 5Linked to original sources

Genetics in rheumatoid arthritis.

The data from the human genome project were published in 2001. Although this achievement will boost research in the genetics of rheumatoid arthritis (RA), most of the work is in progress. Three of the four consortia that are performing linkage studies to identify loci that are transmitted more often to patients than controls have published data on genome-wide searches in few families. Of all the possible candidate genes, the human leukocyte antigen (HLA) class II region was found in the pan-European and the US linkage studies, confirming the previous data from association studies that HLA class II alleles confer risk to RA. Although HLA as a risk factor for RA has been known for a long time, the mechanism by which HLA alleles affect disease risk are controversial. Several papers have been published recently that support the RA-protection hypothesis. Several candidate loci/genes have been suggested from association studies. However, these associations have not been reproduced by different groups in several different cohorts.

Arthritis, Rheumatoid↗

Production of IL-1beta and IL-1Ra as risk factors for susceptibility and progression of relapse-onset multiple sclerosis.

Interleukin-1beta (IL-1beta) is present in multiple sclerosis (MS) lesions. Interleukin-1 receptor antagonist (IL-1Ra) moderates the induction of experimental autoimmune encephalomyelitis (EAE). Here, we show that families that are characterized by high IL-1beta over IL-1Ra production ratio are at 2.2-fold (95% CI, 1.0-4.8; p=0.05) increased risk to have a patient relative with relapse-onset MS than families with a low ratio. It is also related to the reduction of volumetric magnetization transfer ratio (MTR) histogram height, a measure of parenchymal integrity (p=0.04). Those families who combine a high IL-1beta over IL-1Ra ratio with a high tumor necrosis factor (TNF) over IL-10 production ratio have a 6.2-fold (95% CI, 1.8-21; p=0.002) increased risk. Innate production of IL-1beta and IL-1Ra is not related to the outcome of primary progressive MS. Taq1 polymorphism in the IL-1beta gene and the variable number of tandem repeats (VNTR) polymorphism of 86-base pairs within the IL-1Ra gene cannot explain these findings.

Adult↗

Frequency of functional interleukin-10 promoter polymorphism is different between relapse-onset and primary progressive multiple sclerosis.

Interleukin-10 (IL-10) secretion affects the inducibility of experimental autoimmune encephalomyelitis and the outcome of multiple sclerosis (MS). Here, we report that a G to A polymorphism in the IL-10 promoter at position -2849 is significantly associated with low IL-10 production. The frequency of this polymorphism is lower among patients with primary progressive compared with patients with relapse-onset MS and control persons.

Adult↗

Systemic lupus erythematosus: diagnostic application of magnetization transfer ratio histograms in patients with neuropsychiatric symptoms--initial results.

PURPOSE: To explore the diagnostic potential of magnetization transfer ratio (MTR) histogram analysis in patients with neuropsychiatric systemic lupus erythematosus (SLE) by using multivariate discriminant analysis (MDA). MATERIALS AND METHODS: Volumetric magnetization transfer imaging was performed in nine patients with active non-thromboembolic, neuropsychiatric SLE, 10 patients with SLE who had had neuropsychiatric SLE previously, 10 patients with SLE but no history of neuropsychiatric SLE, 10 patients with inactive multiple sclerosis, and 10 healthy control subjects. For each subject, an MTR histogram of the whole brain was generated, and an MDA score was produced for each histogram. Each patient was assigned to a clinical subgroup on the basis of these MDA scores. For assignment, binary comparisons between subgroups were made. The accuracy of this classification method was assessed and compared with that of conventional MTR histogram analysis. RESULTS: With MDA, the success rate of binary classification was 60%-100%, depending on which two groups were compared. When the different clinical subgroups were separated, MDA parameters were always better than conventional MTR histogram parameters, with P values ranging from.05 to less than 1 x 10(-6) of those attained with the best conventional parameter. CONCLUSION: With MDA, MTR histograms of brain tissue may provide diagnostic information for individual patients in the clinical context of SLE.

Adult↗

The effect of corticosteroid medication on quantitative MR parameters of the brain.

BACKGROUND AND PURPOSE: Quantitative MR imaging techniques such as magnetization transfer imaging (MTI), diffusion-weighted imaging (DWI), and MR spectroscopy are promising diagnostic tools for use with patients with diffuse brain diseases such as neuropsychiatric systemic lupus erythematosus (NPSLE). Such patients are often on corticosteroid (CS) treatment. Presently, it is unknown whether CSs per se influence quantitative MR imaging measurements. The aim of this study was to evaluate the effect of low-dose oral CSs on MTI, DWI, and MR spectroscopy parameters of the brain. METHODS: Twenty-seven rheumatoid arthritis (RA) patients with and without CS medication and 15 healthy controls were subjected to conventional MR imaging, whole-brain MTI and DWI, and single-voxel MR spectroscopy. Oral CSs were used by 13 of the RA patients. Univariate analyses with age as a covariate were performed on MTI, DWI, and MR spectroscopy parameters between RA patients with and without CSs and healthy controls. Pearson correlations were calculated between all imaging parameters and duration of disease, duration of CS use, and CS dosage. RESULTS: No significant differences between the groups of subjects or significant correlations with clinical parameters were found for MTI, DWI and MR spectroscopy parameters. CONCLUSION: In this study, we found no evidence for an effect of low-dose oral CSs on whole-brain MTI and DWI histogram parameters and single-voxel MR spectroscopy measurements of the brain. The results of this study demonstrate that it is unlikely that MTI, DWI, and MR spectroscopy parameters reported in NPSLE studies are confounded by low-dose oral CS.

Administration, Oral↗