BackgroundAtherosclerosis is a chronic inflammatory disease, with interleukin 6 (IL‐6) as a major player in inflammation cascade. IL‐6 blockade may reduce cardiovascular risk, but current treatments to block IL‐6 also induce dyslipidemia, a finding with an uncertain prognosis.Methods and ResultsWe aimed to determine the endothelial function responses to the IL‐6–blocking agent tocilizumab, anti–tumor necrosis factor α, and synthetic disease‐modifying antirheumatic drug therapies in patients with rheumatoid arthritis in a 16‐week prospective study. Sixty consecutive patients with rheumatoid arthritis were enrolled. Tocilizumab and anti–tumor necrosis factor α therapy were started in 18 patients each while 24 patients were treated with synthetic disease‐modifying antirheumatic drugs. Forty patients completed the 16‐week follow‐up period. The main outcome was flow‐mediated dilation percentage variation before and after therapy. In the tocilizumab group, flow‐mediated dilation percentage variation increased statistically significantly from a pre‐treatment mean of (3.43% [95% CI, 1.28–5.58] to 5.96% [95% CI, 3.95–7.97]; P=0.03). Corresponding changes were 4.78% (95% CI, 2.13–7.42) to 6.75% (95% CI, 4.10–9.39) (P=0.09) and 2.87% (95% CI, −2.17 to 7.91) to 4.84% (95% CI, 2.61–7.07) (P=0.21) in the anti–tumor necrosis factor α and the synthetic disease‐modifying antirheumatic drug groups, respectively (both not statistically significant). Total cholesterol increased significantly in the tocilizumab group from 197.5 (95% CI, 177.59–217.36) to 232.3 (201.62–263.09) (P=0.003) and in the synthetic disease‐modifying antirheumatic drug group from 185.8 (95% CI, 169.76–201.81) to 202.8 (95% CI, 176.81–228.76) (P=0.04), but not in the anti–tumor necrosis factor α group. High‐density lipoprotein did not change significantly in any group.ConclusionsEndothelial function is improved by tocilizumab in a high‐risk population, even as it increases total cholesterol and low‐density lipoprotein levels.
The HLA-DRB1 alleles encoding an amino acid sequence (QKRAA/QRRAA/RRRAA) at position 70 74 of the third hypervariable region of the β1 chain of the HLA-DRB1 gene, called shared epitope (SE), are associated with increased susceptibility to and severity of rheumatoid arthritis (RA) in different populations. Objective: To determine the frequency of HLA-DRB1 alleles in Brazilian patients with RA and their association with rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA). Methods: Four hundred and twelve patients with RA (ACR 1987) and 215 controls were included. HLA-DRB1 typing was performed by use of polymerase chain reaction (PCR) with specifi c primers and hybridization with sequence-specifi c oligonucleotide probe (SSOP). ACPA was measured by use of the ELISA technique and RF by nephelometry. The statistical analysis comprised the chi-square and Student t tests and logistic regression. Results: HLA-DRB1*04:01, *04:04, *04:05 alleles were associated with RA (P < 0.05); despite the wide confi dence interval, it is worth noting the association between the DRB1*09:01 allele and RA (P < 0.05). HLA-DRB1 SE+ alleles were observed in 62.8% of the patients and in 31.1% of controls (OR 3.62; P < 0.001) and were associated with ACPA (OR 2.03; P < 0.001). DRB1-DERAA alleles showed a protective effect against RA (OR 0.42; P < 0.001). Conclusion: In a sample of Brazilian patients with RA, most of whom of mixed heritage, HLA-DRB1 SE+ alleles were associated with susceptibility to disease and presence of ACPA.
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