The aim of this study was to investigate whether vitamin D deficiency (VDD) is associated with acute ischemic stroke, inflammatory markers, and short-term outcome. 168 acute ischemic stroke patients and 118 controls were included. The modified Rankin Scale (mRS) was applied up to 8 h of admission (baseline) and after three-months follow-up, and blood samples were obtained up to 24 h of admission to evaluate serum levels of 25-hydroxivitamin D [25(OH)D] and inflammatory markers. Vitamin D levels classified the individuals in sufficient (VDS ≥ 30.0 ng/mL), insufficient (VDI 20.0-29.9 ng/mL), and deficient (VDD < 20.0 ng/mL) status. Patients had lower levels of 25(OH)D, higher frequency of VDD (43.45% vs. 5.08%, OR: 16.64, 95% CI: 5.66-42.92, p < 0.001), and higher inflammatory markers than controls (p < 0.05). Patients with VDD showed increased high sensitivity C-reactive protein (hsCRP) levels than those with VDS status (p = 0.043); those with poor outcome presented with lower 25(OH)D levels than those with good outcome (p = 0.008); moreover, 25(OH)D levels were negatively correlated with mRS after three-months follow-up (r = -0.239, p = 0.005). The associations between VDD and higher hsCRP levels and between 25(OH)D levels and poor outcome at short-term in acute ischemic stroke patients suggest the important role of vitamin D in the inflammatory response and pathophysiology of this ischemic event.

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 CCR5Δ32 polymorphism with the susceptibility to SLE and the activity of disease in female Southern Brazilian patients. 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 CCR5Δ32 genotypes. The CCR5Δ32 polymorphism was determined from genomic DNA using a polymerase chain reaction. 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 [CCR5/CCR5 vs. CCR5/CCR5Δ32 + CCR5Δ32/CCR5Δ32: p = 0.0081, odds ratio 3.604 (95 % confidence interval 1.321-9.4836)]. The frequencies of the CCR5 and the CCR5Δ32 alleles were 93.2 and 6.8 % among the patients, and 98.1 and 1.9 % among the controls, respectively (p = 0.0047, OR 3.758, 95 % CI 1.409-10.80). Patients carrying the genotypes with the CCR5Δ32 allele 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 significant (p > 0.05). 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.

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.

Gender, age, and BMI influence serum hs-CRP level in healthy individuals and these variables should be considered for the interpretation of hs-CRP values. The results reinforce the importance in evaluating whether these differences in hs-CRP levels could contribute to alter the cardiovascular risk criteria and clinical outcomes, and whether hs-CRP thresholds for cardiovascular risk assessment should be adjusted for different gender and body mass index groups.

Abstract. the association of the tumor necrosis factor β (tnF-β) nco1 genetic polymorphism with susceptibility to sepsis was evaluated in 60 consecutive patients diagnosed with sepsis and in 148 healthy blood donors. Genomic dna was extracted from peripheral blood cells and a 782 base-pair fragment of the tnF-β gene was amplified by PCR. The pcr products were subjected to nco1 restriction digestion and analysed by restriction fragment length polymorphism analysis. tumor necrosis factor α (tnF-α) and the c-reactive protein (crp) serum levels were also determined by EliSa and nephelometry, respectively. among the septic patients, the allelic frequencies of tnFB1 and tnFB2 were 0.2833 and 0.7166, respectively, and they differed from those observed in the blood donors (p=0.0282). the tnFB2 allele frequency was higher in the septic patients than in the blood donors [odds ratio=1.65 (ci 95% 1.02-2.69), p=0.0315]. the tnF-α and crp serum levels and the apachE ii and SOFa clinical scores did not differ in the patients with the tnFB1 or tnFB2 alleles (p>0.05). the results suggest that the tnFB2 allele is associated with susceptibility to sepsis, but it was not found to be associated with the immunological and clinical biomarkers of the disease.

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.

Polymorphisms in genes coding for pro-inflammatory molecules represent important factors for the pathogenesis and outcome of stroke. The aim of this study was to evaluate the relationship between the tumor necrosis factor beta (TNF-β) NcoI (rs909253) polymorphism with inflammatory and metabolic markers in acute ischemic stroke. Ninety-three patients and 134 controls were included. The TNF-β polymorphism was determined using PCR-RFLP with NcoI restriction enzyme. Stroke subtypes and neurological deficit score were evaluated. White blood cell counts, erythrocyte sedimentation rate (ESR), plasma levels of IL-6 and TNF-α, serum high sensitivity C-reactive Protein (hsCRP), serum lipid profile, plasma levels of glucose and insulin, and homeostatic model assessment of insulin resistance (HOMA-IR) were determined. Stroke patients presented higher white blood cell counts, hsCRP, ESR, glucose, insulin, and HOMA-IR, and lower HDL cholesterol than controls (p < 0.01). There was no difference in genotypic and allelic frequency of TNF-β NcoI polymorphism among patients and controls (p > 0.05). However, stroke patients carrying the TNFB2/B2 genotype presented higher levels of TNF-α, white blood cell counts, total cholesterol, LDL cholesterol, glucose, insulin, and HOMA-IR than those with other genotypes (p < 0.05). White blood cells, IL-6, hsCRP, and ESR were positively correlated with the neurological deficit of the patients (p < 0.05). Taken together, TNF-β NcoI polymorphism, by itself, was not associated with increased susceptibility for stroke development. However, the homozygous genotype for the allele TNFB2 was associated with higher expression of classical inflammatory and metabolic markers of development and outcome of stroke than other genotypes. The identification of variant alleles might allow both better prediction of susceptibility for stroke as well the identification of novel stroke mechanisms that could be target to new therapeutic approaches. Stroke patients carrying the TNFB2 variant allele could have a beneficial effect with the anti-inflammatory therapies in the early inflammatory phase of stroke.

The aims of the present study were to evaluate biomarkers of oxidative and nitrosative stress in systemic lupus erythematosus (SLE) patients, in particular products of DNA/RNA oxidative damage and their correlation with disease activity. This study included 188 controls and 203 patients; 153 with inactive SLE (SLEDAI < 6) and 50 with active SLE (SLEDAI ≥ 6) without renal impairment. Oxidative stress was assessed by tert-butyl hydroperoxide-initiated by chemiluminescence, advanced oxidation protein products (AOPP), total radical-trapping antioxidant parameter (TRAP), nitric oxide metabolites (NOx), and DNA/RNA oxidation products. Patients with SLE showed increased oxidative stress, as demonstrated by the augmentation of lipid hydroperoxides ( p < 0.0001) and AOPP ( p < 0.001) and reduced total antioxidant capacity ( p < 0.0001), without differences between patients with active disease and in remission. NOx levels and DNA/RNA oxidation products were inversely and independently associated with disease activity ( p < 0.0001 and p = 0.021, respectively), regardless of BMI and prednisone use. The linear regression analysis showed that about 5% of the SLEDAI score can be explained by the levels of DNA/RNA oxidation products ( r:0.051; p = 0.002) and about 9% of this score by the levels of NOx ( r:0.091; p < 0.0001). This study provides evidence for an inverse association between serum NOx levels and DNA/RNA oxidation products and SLE disease activity, suggesting that oxidative/nitrosative stress markers may be useful in evaluating SLE disease activity and progression of the disease.