Interferon regulatory factor 5 gene variants rs2004640 and rs4728142 are associated with carotid intima media thickness but not with cardiovascular events in rheumatoid arthritis.

Objectives: Rheumatoid arthritis (RA) is associated with cardiovascular (CV) morbidity and mortality. Interferon regulatory factor 5 (IRF5) gene polymorphisms rs2004640 and rs4728142 have been associated with autoimmune diseases, but also with atherosclerosis. Differences in IRF5 gene expression can lead to the production of different interferons and might play a role in the atherogenic process in RA.

Sex differences in the human peripheral blood transcriptome.

Background: Genomes of men and women differ in only a limited number of genes located on the sex chromosomes, whereas the transcriptome is far more sex-specific. Identification of sex-biased gene expression will contribute to understanding the molecular basis of sex-differences in complex traits and common diseases.

Results: Sex differences in the human peripheral blood transcriptome were characterized using microarrays in 5,241 subjects, accounting for menopause status and hormonal contraceptive use.

Using biomarkers to predict progression from clinically isolated syndrome to multiple sclerosis.

Background: Detection of brain lesions disseminated in space and time by magnetic resonance imaging remains a cornerstone for the diagnosis of clinically definite multiple sclerosis. We have sought to determine if gene expression biomarkers could contribute to the clinical diagnosis of multiple sclerosis.

Methods: We employed expression levels of 30 genes in blood from 199 subjects with multiple sclerosis, 203 subjects with other neurologic disorders, and 114 healthy control subjects to train ratioscore and support vector machine algorithms.

Type I interferons have no major influence on humoral autoimmunity in rheumatoid arthritis.

Objective: Type I IFNs have recently been implicated in autoantibody-mediated diseases such as SLE. As half the RA patients display a type I IFN(high) signature, we investigated in a pilot study if type I IFN determines the autoantibody response in RA.

Methods: Serum and peripheral blood cells were obtained from 52 RA patients, with paired samples before and after infliximab treatment in 21 patients.

B lymphocyte autoimmunity in rheumatoid synovitis is independent of ectopic lymphoid neogenesis.

B lymphocyte autoimmunity plays a crucial role in the pathogenesis of rheumatoid arthritis. The local production of autoantibodies and the presence of ectopic lymphoid neogenesis in the rheumatoid synovium suggest that these dedicated microenvironments resembling canonical lymphoid follicles may regulate the initiation and maturation of B cell autoimmunity. In this study, we assessed experimentally the relevance of ectopic lymphoid neogenesis for B cell autoimmunity by a detailed structural, molecular, and serological analysis of seropositive and seronegative human synovitis.

CCL5 and CCR5 genotypes modify clinical, radiological and pathological features of multiple sclerosis.

Chemokines mediate selective recruitment of leukocyte subsets into the CNS during inflammatory episodes. We hypothesised that functional polymorphisms in CCR5 and CCL5 influence perivascular leukocyte infiltration, inflammation, axonal loss, and remyelination, and disease course. Therefore, we determined genotypes at four possibly functional polymorphisms in CCR5 and CCL5 for 637 patients and 92 brain donors with multiple sclerosis (MS).

Differentially methylated alleles in a distinct region of the human interleukin-1alpha promoter are associated with allele-specific expression of IL-1alpha in CD4+ T cells.

Cytokine secretion profiles of activated T cells are critical for maintaining the immunologic balance between protection and tolerance. In mice, several cytokines have been reported to exhibit monoallelic expression. Previously, we found that the human interleukin-1 alpha (IL1A) gene exhibits a stable allele-specific expression pattern in CD4+ T-cell clones.

Association of autoantibodies to glucose-6-phosphate isomerase with extraarticular complications in rheumatoid arthritis.

Objective: In the K/BxN mouse model, autoantibodies against glucose-6-phosphate isomerase (GPI) cause arthritis. The relevance of this model for human disease remains a subject of controversy. We set out to determine whether GPI autoantibodies occur in patients with rheumatoid arthritis (RA) and, if so, at what stage of the RA.

Tumor necrosis factor-alpha gene polymorphisms in relation to periodontitis.

Background: Genetic polymorphisms for cytokines have been proposed as potential genetic markers for destructive periodontal disease. The present aim was to investigate 4 bi-allelic polymorphisms in the TNF-alpha gene in relation to susceptibility for and severity of periodontitis. The polymorphisms were all transitions from G to A, 3 in the promoter positions: -376, -308, -238; and one in the first intron at position +489.