Francieli Delongui

Serum Levels of High Sensitive C Reactive Protein in Healthy Adults From Southern Brazil

With the emergence of more sensitive assay techniques, it has been shown that C reactive protein (CRP) is present at low levels in the serum of all the clinically healthy individuals.

Influence of Insulin Resistance and TNF-α on the Inflammatory Process, Oxidative Stress, and Disease Activity in Patients with Rheumatoid Arthritis

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.

Human Leukocyte Antigen Class I and Class II Polymorphisms and Serum Cytokine Profiles in Cervical Cancer

Only a small proportion of women who are exposed to infection with high-risk human papillomavirus (HR-HPV) progress to persistent infection and develop cervical cancer (CC). The immune response and genetic background of the host may affect the risk of progression from a HR-HPV infection to lesions and cancer. However, to our knowledge, no studies has been conducted to evaluate the relationship between variability of human leukocyte antigens (HLA) genes and serum cytokine expression in this pathology. In the current study, we examined the associations of HLA alleles and haplotypes including Class I (HLA-A, -B and -C) and II (HLA-DRB1, -DQA1 and -DQB1) with serum levels of cytokines interleukin (IL)-6, tumor necrosis factor-α (TNF-α), IL-10 and IL-17 as well as risks of HPV infections, lesions and CC among admixed Brazilian women. HLA polymorphisms were associated with an increased risk or protection from HPV, lesions and CC. Additionally, we demonstrated a potential association of a HLA class I haplotype (HLA-B*14-C*08) with higher IL-10 cytokine serum levels in cervical disease, suggesting an association between HLA class I and specific cytokines in cervical carcinogenesis. However, larger studies with detailed HPV types coupled with genetic data are needed to further evaluate the effects of HLA and CC by HPV genotype.

328 Ccr5δ32 (rs333) polymorphism is associated with susceptibility to systemic lupus erythematosus in female brazilian patients

Background and aims The role of CCR5Δ32(rs333) polymorphism in the pathogenesis of systemic lupus erythematosus (SLE) has been evaluated worldwide. The aim of this study was to determine the association between CCR5Δ32polymorphism with the susceptibility to SLE and the activity of disease in female Southern Brazilian patients. Methods The study enrolled 169 female SLE patients and 132 unrelated female healthy individuals. Baseline clinical, laboratorial characteristics, and the SLE activity (determined using the SLEDAI) were evaluated according to the CCR5Δ32genotypes. The CCR5Δ32 polymorphism was determined from genomic DNA using a polymerase chain reaction. Results The frequencies of the genotypes CCR5/CCR5, CCR5/CCR5Δ32 and CCR5Δ32/CCR5Δ32 were 87.6%, 11.8%, and 0.6%, respectively, among the patients, and 96.2%, 3.8%, and 0.0%, respectively among the controls, [p=0.0116, odds ratio:3.432 (95% confidence interval:1.252–9.40). Patients carrying the CCR5/CCR5Δ32 and CCR5Δ32/CCR5Δ32 genotypes presented earlier age of onset of disease (p=0.0293) and higher levels of anti-dsDNA (p=0.0255), than those carrying the wild type genotype. When the analysis was adjusted for ethnicity, only the age at onset of disease remained associated with the CCR5Δ32 polymorphism (p<0.05); patients with variant CCR5Δ32 allele (heterozygous and homozygous), presented lower age at onset of disease than those with the wild type genotype. Conclusions The results suggest that the CCR5Δ32 polymorphism might be associated with SLE genetic predisposition among female Brazilian patients and the age at onset of the disease; however, this genetic variant was not associated with the activity of SLE in this population.

327 Genetic polymorphism +1444ct in the c – reactive protein is associated with the susceptibility for systemic lupus erythematosus and disease activity

Background and aims The gene C-reactive protein (CRP), located at 1q23-24, is a candidate to be investigated as a susceptibility locus for systemic lupus erythematosus (SLE). The aim of the study was to evaluate the association between the +1444CT CRP polymorphism with the susceptibility for SLE, disease activity, and CRP serum levels. Methods The study enrolled 176 SLE patients and 223 healthy controls from Brazilian population. SLE disease activity (SLEDAI), clinical and laboratorial characteristics were evaluated. The +1444CT CRP polymorphism was determined using polymerase chain reaction and restriction fragment length polymorphism. Results The frequency of CC vs. TT genotypes and the C vs. T allele among the patients differed from the controls (p=0.0201 and p=0.0072, respectively). Patients carrying the T allele presented higher CRP (p=0.017) and showed a trend toward higher IL-6 compared with patients carrying the C allele (p=0.057). The increased CRP was independently of the IL-6 in these subgroups of patients. SLE patients carrying the CC genotype showed positive correlation between CRP and C4 levels (p=0.039), while those with T allele presented a trend toward a negative correlation between CRP and C3 and C4 (p=0.056 and p=0.073, respectively); and a trend toward positive correlation with anti-nucleosome and anti-dsDNA (p=0.052 and p=0.091, respectively). Conclusions Our data showed that +1444CT CRP polymorphism was associated with SLE susceptibility and CRP levels, as well as CRP levels were associated with disease activity, suggesting that this polymorphism may play a role in the pathophysiology of SLE, which may be used as a possible marker of disease activity.