Influence of TNF and IL17 Gene Polymorphisms on the Spondyloarthritis Immunopathogenesis, Regardless of HLA-B27, in a Brazilian Population

Background and Objectives. Spondyloarthritis (SpA) represents a heterogeneous group of immune-mediated inflammatory diseases that have overlapping clinical features, genetic predisposition, and pathogenic mechanisms. Hence, we investigated, through a case-control study, whether single-nucleotide polymorphisms of TNF and IL17 genes are associated with SpA, ankylosing spondylitis (AS), and psoriatic arthritis (PsA) in a mixed Brazilian population. Methods. Genotyping of TNF-308 (rs1800629), TNF-238 (rs361525), IL17A (rs2275913), IL17F (rs763780), and HLA-B27 polymorphisms was performed in 243 patients with SpA and 210 controls from Southern Brazil using SSOP-Luminex (One Lambda) and PCR-SSP assays. Results. Significant associations were confirmed between the HLA-B27 marker and SpA, AS, and PsA diseases. While TNF-308 (rs1800629) AA/GA, IL17A (rs2275913) AA/GA, and IL17F (rs763780) CC/TC genotype frequencies were associated, in the dominance inheritance model, with SpA and AS, regardless of gender, the presence of HLA-B27, TNF-238 (rs361525) GA/AA, IL17A (rs2275913) AA/GA, and IL17F (rs763780) genotypes was associated with PsA. Conclusion. In this Brazilian population, TNF and IL17 gene polymorphisms responsible for the expression of important inflammatory cytokines were associated with overall SpA, and, specifically, with AS and PsA, regardless of gender and HLA-B27. However, future larger studies with different ethnicities may be necessary to confirm these genetic associations

Acetylcysteine for Prevention of Renal Outcomes in Patients Undergoing Coronary and Peripheral Vascular Angiography Main Results From the Randomized Acetylcysteine for Contrast-Induced Nephropathy Trial (ACT)

Background-It remains uncertain whether acetylcysteine prevents contrast-induced acute kidney injury. Methods and Results-We randomly assigned 2308 patients undergoing an intravascular angiographic procedure with at least 1 risk factor for contrast-induced acute kidney injury (age >70 years, renal failure, diabetes mellitus, heart failure, or hypotension) to acetylcysteine 1200 mg or placebo. The study drugs were administered orally twice daily for 2 doses before and 2 doses after the procedure. The allocation was concealed (central Web-based randomization). All analysis followed the intention-to-treat principle. The incidence of contrast-induced acute kidney injury (primary end point) was 12.7% in the acetylcysteine group and 12.7% in the control group (relative risk, 1.00; 95% confidence interval, 0.81 to 1.25; P = 0.97). A combined end point of mortality or need for dialysis at 30 days was also similar in both groups (2.2% and 2.3%, respectively; hazard ratio, 0.97; 95% confidence interval, 0.56 to 1.69; P = 0.92). Consistent effects were observed in all subgroups analyzed, including those with renal impairment. Conclusions-In this large randomized trial, we found that acetylcysteine does not reduce the risk of contrast-induced acute kidney injury or other clinically relevant outcomes in at-risk patients undergoing coronary and peripheral vascular angiography.Ministério da Saúde do BrasilBrazilian Ministry of Healt