Influence of Insulin Resistance and TNF- α

The aim of this study was to evaluate the involvement of TNF-α and insulin resistance (IR) in the inflammatory process, oxidative stress, and disease activity in patients with rheumatoid arthritis (RA). This cross-sectional study included 270 subjects (control group, n=97) and RA patients (n=173). RA patients were divided into four groups: the first group without IR and not using antitumor necrosis factor-α (TNF-) (G1, IR− TNF−); the second group without IR and using anti-TNF-α (G2, IR- TNF+); the third group with IR and not using anti-TNF-α (G3, IR+ TNF-); and the fourth group with IR and using anti-TNF-α (G4, IR+ TNF+). G3 and G4 had higher (p<0.05) advanced oxidation protein products (AOPPs) and oxidative stress index (OSI) compared to G1. G4 group presented higher (p<0.05) AOPPs and OSI than G2. TRAP was significantly lower in G3 compared to G1. Plasma TNF-α levels were significantly higher in G4 and G2 compared to G1 (p<0.0001) and G3 (p<0.0001 and p<0.01, resp.). The presence of insulin resistance was robustly associated with both oxidative stress and TNF-α levels. More studies are warranted to verify if IR can be involved in therapeutic failure with TNF-α inhibitors. This trial is registered with Brazilian Clinical Trials Registry Register number RBR-2jvj92

TGFB1 +869 T > C (rs1800470) variant is independently associated with susceptibility, laboratory activity, and TGF-β1 in patients with systemic lupus erythematosus

The aim of this study was to evaluate the association of the +869 T > C (rs1800470) and −509 C > T (rs1800469) TGFB1 variants, individually or in haplotypes structure, with susceptibility, autoantibodies, disease activity, and TGF-β1 plasma levels in patients with systemic lupus erythematosus (SLE). The study included 203 patients with SLE and 165 healthy controls. TGFB1 variants were determined by real-time polymerase chain reaction (qPCR). Plasma levels of TGF-β1 were determined using immunofluorimetric assay. The TGFB1 + 869 CC genotype was associated with SLE susceptibility (OR: 1.710, 95%CI: 1.020–2.866, p = 0.042) and with reduction of C4 (p = 0.040) and TGF-β1 levels (p = 0.044). In addition, patients with TGFB1 + 869 TC and CC genotypes and positive anti-dsDNA had lower TGF-β1 levels than those with TT (p = 0.004). TGFB1 −509 TT genotype was associated with reduced levels of C4 (p = 0.032). There was no association between haplotypes and clinical and laboratory parameters. Our data demonstrated that the TGFB1 + 869 T > C variant could be used as a genetic marker for SLE susceptibility and both variants as predictors of laboratory activity. This is the first study to demonstrate that TGF-β1 levels could be modulated by the interaction between TGFB1 + 869 C allele, in homozygosity, or heterozygosity, and the presence of anti-dsDNA