MBL2 gene polymorphisms and its relation to infection in Brazilian systemic lupus erythematosus patients: A 10-years follow-up study.

INTRODUCTION: Systemic lupus erythematosus (SLE) is a multifactorial disease and MBL2 genetic variants, which are associated to differential peripheral MBL levels, potentially affect its etiology and increase infection risk in this population. OBJECTIVE: To evaluate the potential association of MBL2 polymorphisms of the coding and promoter gene region and haplotypes on hospitalization, number of admission and days of admission for major infection causes in Brazilian SLE patients. Methods: 325 SLE patients from a southern Brazilian outpatient SLE clinic were genotyped in 2006 for MBL2 gene polymorphisms from coding and promoter region (rs1800450, rs1800451, rs5030737, rs11003125, and rs7096206) and followed until 2016. Clinical and laboratory data from each patient were obtained and information regarding the need for hospitalization, the number of admissions and number of days admitted for infection treatment were compiled and compared with MBL2 gene polymorphisms and haplotypes. A linear regression analysis was constructed considering the variables of bivariate which demonstrated an association (p<0.05) and variables which had a theoretical basement. RESULTS: No difference was found in polymorphism prevalence when comparing the group that was admitted for infection treatment and the group who did not. Allele C, and haplotypes LY and HY correlated with more infection hospitalizations [wild-type homozygosis for C: 2 (IQR 1-3), heterozygosis for C: 3 (IQR 2-6) p=0.038; LY 2 (IQR 1-3) p=0.049; HY 2 (IQR 1-3) p=0.005] and haplotype HY carriers stayed fewer days in hospital for infection treatment: 18 (IQR 10-38) p=0.041. When linear regression was applied HY associated with shorter admission time for infections (-18.11 days, p=0.021) and HY (-1.52 admission, p 0.001) carriers with older age at diagnosis had less admissions for infection (HY regression model: -0.42, p=0.006; LY regression model -0.04, p=0.010; -0.04, p=0.013). CONCLUSION: The presence of the HY promoter haplotype associated to fewer in hospital care for infection treatment probably due to higher MBL plasma levels. Also, HY haplotype and older age at SLE diagnosis is related to less admissions for infection. This factor should be taken into consideration, since infection is a very import cause of mortality in SLE patients being also related to aggressive immunosuppressive treatment.

RvD1 treatment during primary infection modulates memory response increasing viral load during respiratory viral reinfection.

Resolvin D1 (RvD1), which is biosynthesized from essential long-chain fatty acids, is involved in anti-inflammatory activity and modulation of T cell response. Memory CD8+ T cells are important for controlling tumor growth and viral infections. Exacerbated inflammation has been described as impairing memory CD8+ T cell differentiation. This study aimed to verify the effects of RvD1 on memory CD8+ T cells in vitro and in vivo in a respiratory virus infection model. Peripheral blood mononuclear cells were treated at different time points with RvD1 and stimulated with anti-CD3/anti-CD28 antibodies. Pre-treatment with RvD1 increases the expansion of memory CD8+ T cells. The IL-12 level, a cytokine described to control memory CD8+ T cells, was reduced with RvD1 pre-treatment. When the mTOR axis was inhibited, the IL-12 levels were restored. In a respiratory virus infection model, Balb/c mice were treated with RvD1 before infection or after 7 days after infection. RvD1 treatment after infection increased the frequency of memory CD8+ T cells in the lung expressing II4, II10, and Ifng. During reinfection, RvD1-treated and RSV-infected mice present a high viral load in the lung and lower antibody response in the serum. Our results show that RvD1 modulates the expansion and phenotype of memory CD8+ T cells but contributed to a non-protective response after RSV reinfection.

Heme oxygenase 1 is expressed in murine erythroid cells where it controls the level of regulatory heme.

Heme is essential for the function of all aerobic cells. However, it can be toxic when it occurs in a non-protein-bound form; cells maintain a fine balance between heme synthesis and catabolism. The only physiological mechanism of heme degradation is by heme oxygenases (HOs). The heme-inducible isoform, HO-1, has been extensively studied in numerous nonerythroid cells, but virtually nothing is known about the expression and potential significance of HO-1 in developing red blood cells. We have demonstrated that HO-1 is present in erythroid cells and that its expression is upregulated during erythroid differentiation. Overexpression of HO-1 in erythroid cells impairs hemoglobin synthesis, whereas HO-1 absence enhances hemoglobinization in cultured erythroid cells. Based on these results, we conclude that HO-1 controls the regulatory heme pool at appropriate levels for any given stage of erythroid differentiation. In summary, our study brings to light the importance of HO-1 expression for erythroid development and expands our knowledge about the fine regulation of hemoglobin synthesis in erythroid cells. Our results indicate that HO-1 plays an important role as a coregulator of the erythroid differentiation process. Moreover, HO-1 expression must be tightly regulated during red blood cell development.

HIV voluntary counseling and testing of couples during maternal labor and delivery: the TRIPAI Couples study.

BACKGROUND: Women in Brazil are routinely tested for HIV-1 during pregnancy with rapid testing repeated during labor in some settings. Partner testing is not routinely offered. The peripartum period provides opportunity for HIV testing of couples. METHODS: A cross-sectional study was conducted in a large public hospital in southern Brazil. HIV rapid testing was offered to all pregnant women in labor. Male partners of women who consented to partner inclusion were offered testing. Within HIV-serodiscordant couples, HIV-negative individuals were evaluated for the delta-32 base-pair CCR5 deletion allele. RESULTS: From February to September 2009, 2888 women delivered, with 1729 eligible women approached for study participation; 1648 (95%) HIV-negative women consented to partner testing and 66% of partners accepted testing. Seven HIV-infected men (0.6%) with no prior diagnosis were identified. Testing strategies uncovered 7 additional serodiscordant couples, 4 HIV-infected women diagnosed at delivery, and 3 HIV-infected men who had not disclosed their status to their partners, for a total serodiscordance rate of 1.3% in 1101 couples. No cases of acute maternal or infant infection were noted. No delta-32 base-pair deletions were identified in 14 HIV-negative partners in serodiscordant relationships. Parameters associated with increased acceptance of partner testing included higher income (P = 0.003), education (P < 0.0001), stable relationships of longer duration (P = 0.001), and female support of partner testing (P < 0.0001). CONCLUSIONS: Testing of couples at the time of labor and delivery is a feasible public health strategy in areas of moderate-to-high HIV prevalence, which can potentially prevent acute infections in men, women, and infants.

The isolation of stem cells from human deciduous teeth pulp is related to the physiological process of resorption.

INTRODUCTION: The aim of this study was to isolate and grow cells from sound human deciduous teeth pulp with different levels of resorption and evaluate stem cell parameters. METHODS: Pulp tissue was removed from 30 different patients, aged from 6 to 12 years. From all the teeth, 21 were in advanced levels of resorption (group 1), and the remaining nine teeth did not show any visible resorption (group 2). Pulp tissue was removed and dissociated, and the suspension was seeded onto 12-well plates. The phenotype of the cells (n = 5) was analyzed on fifth and tenth passages by flow cytometry for clusters of differentiation (CD)29/PE, CD34/PE, CD44/FITC, CD45/FITC, CD90/FITC, CD117/PE, CD133/PE, CD146/FITC, CD184/PE, Stromal Cell Surface Marker 1 (STRO-1)/FITC and human leukocyte antigen major histocompatibility complex class II surface receptor (HLA-DR)/FITC, and by reverse transcription-polymerase chain reaction (RT-PCR) for octamer-binding transcription factor 4 (OCT-4). On the same passages, cells were differentiated into adipocytes, osteoblasts, and chondrocytes. RESULTS: Cell isolation was successful in 25 samples, but only 17 of these reached 90% confluence. It was not possible to establish cell culture from group 2. Cells on both fifth and tenth passages were positive for CD29, CD44, and CD90 and also for the expression of OCT-4. Moderate labeling was observed for CD117 and CD133, whereas a low expression was detected for CD34, CD45, HLA-DR, CD184, CD146, and STRO-1. All cultures differentiated into three cell types. CONCLUSIONS: The isolated pulp cells can be considered stem cells. The facility for obtaining cells seems to be related to the root resorption process, so, therefore, the cells from group 1 were able to proliferate in vitro, whereas group 2 cells were not.