title: Differential gene expression of peripheral blood mononuclear cells from rheumatoid arthritis patients may discriminate immunogenetic, pathogenic and treatment features.
abstract: This study aimed to evaluate the association between the differential gene expression profiling of peripheral blood mononuclear cells of rheumatoid arthritis patients with their immunogenetic (human leucocyte antigen shared-epitope, HLA-SE), autoimmune response [anti-cyclic citrullinated peptide (CCP) antibodies], disease activity score (DAS-28) and treatment (disease-modifying antirheumatic drugs and tumour necrosis factor blocker) features. Total RNA samples were copied into Cy3-labelled complementary DNA probes, hybridized onto a glass slide microarray containing 4500 human IMAGE complementary DNA target sequences. The Cy3-monocolour microarray images from patients were quantified and normalized. Analysis of the data using the significance analysis of microarrays algorithm together with a Venn diagram allowed the identification of shared and of exclusively modulated genes, according to patient features. Thirteen genes were exclusively associated with the presence of HLA-SE alleles, whose major biological function was related to signal transduction, phosphorylation and apoptosis. Ninety-one genes were associated with disease activity, being involved in signal transduction, apoptosis, response to stress and DNA damage. One hundred and one genes were associated with the presence of anti-CCP antibodies, being involved in signal transduction, cell proliferation and apoptosis. Twenty-eight genes were associated with tumour necrosis factor blocker treatment, being involved in intracellular signalling cascade, phosphorylation and protein transport. Some of these genes had been previously associated with rheumatoid arthritis pathogenesis, whereas others were unveiled for future research.
authors.affiliation: Molecular Immunogenetics Group, Department of Genetics, Faculty of Medicine, University of São Paulo.
authors.forename: Cristina Moraes
authors.initials: CM
authors.lastname: Junta
authors.forename: Paula
authors.initials: P
authors.lastname: Sandrin-Garcia
authors.forename: Ana Lúcia
authors.initials: AL
authors.lastname: Fachin-Saltoratto
authors.forename: Stephano Spanó
authors.initials: SS
authors.lastname: Mello
authors.forename: Renê D R
authors.initials: RD
authors.lastname: Oliveira
authors.forename: Diane Meyre
authors.initials: DM
authors.lastname: Rassi
authors.forename: Silvana
authors.initials: S
authors.lastname: Giuliatti
authors.forename: Elza Tiemi
authors.initials: ET
authors.lastname: Sakamoto-Hojo
authors.forename: Paulo
authors.initials: P
authors.lastname: Louzada-Junior
authors.forename: Eduardo Antonio
authors.initials: EA
authors.lastname: Donadi
authors.forename: Geraldo A S
authors.initials: GA
authors.lastname: Passos
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006684:HLA-DR Antigens / Q000032:analysis; D059811:HLA-DRB1 Chains; D006650:Histocompatibility Testing; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010456:Peptides, Cyclic / Q000276:immunology; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D018501:Antirheumatic Agents; D001323:Autoantibodies; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D010456:Peptides, Cyclic; D014409:Tumor Necrosis Factor-alpha; C487763:cyclic citrullinated peptide