HLA profile in patients with AIDS and tuberculosis

Studies carried out in various populations have reported an association between some HLA specificities and susceptibility to tuberculosis. We investigated the class I and class II HLA profile in Brazilian patients of various ethnic backgrounds who had AIDS and tuberculosis. Twenty-two adult patients with AIDS and tuberculosis (Group I), 103 patients with AIDS without tuberculosis (Group II) and 423 healthy individuals not infected with HIV (Group III) were evaluated. Diagnosis of HIV infection was made by ELISA, confirmed by a gelatin particle agglutination test. Diagnosis of tuberculosis was made based on clinical/radiological presentation and direct bacilloscopy or clinical specimen cultures. Class I antigens were typed by microlymphotoxicity. Class II alleles were characterized by the polymerase chain reaction (PCR). Differences in frequency of HLA specificities between groups were found in the following antigens/alleles: Group I x Group II: HLA-A31 - p=0.026; HLA-B41 - p= 0.037; HLA-DRB1*10 - p=0.037; HLA-DQB1*5 - p=0.009. Group I x Group III (control): HLA-A31 - p = 0.000008; odds ratio (OR)=31.75; HLA-B41 - p=0.003; HLA-DQB1*5 - p=0.02. HLA-A31 and HLA-B41 antigens and the HLA-DRB1*10 and HLA-DQB1*05 alleles were over-represented in patients with AIDS and tuberculosis (Group I), suggesting that these HLA molecules are associated with susceptibility to tuberculosis in Brazilian patients with AIDS

Data on HLA class I/II profile in Brazilian pemphigus patients

AbstractPemphigus are blistering autoimmune diseases related with genetic and environmental factors. Here we describe HLA genotyping in pemphigus patients. First, we review the HLA class I/II data on pemphigus reported in Brazilian samples and then present the HLA class I (-A, -B, -C) and class II (-DRB1, -DQA1, -DQB1) alleles related to susceptibility/resistance to pemphigus by comparing 86 patients with pemphigus foliaceus, 83 patients with pemphigus vulgaris, and 1592 controls from the northeastern region of the state of São Paulo, Southeastern Brazil. The data presented here are related to the manuscript “Differential HLA class I and class II associations in Pemphigus Foliaceus and Pemphigus Vulgaris patients from a prevalent Southeastern Brazilian region” Brochado et al. (2016) [1]

Fatores imunogenéticos associados ao diabetes mellitus do tipo 1

Type 1 diabetes mellitus has been considered an organ-specific autoimmune disease derived from the selective destruction of pancreatic beta cells. It presents a complex pathogenesis, involving the participation of several factors, including the immunogenetic susceptibility with strong association to histocompatibility genes (HLA), environmental events and autoimmune response with the presence of autoantibodies and/or autoreactive lymphocytes, culminating in metabolic abnormalities. In this study, the literature review describes mechanisms through which some factors cause susceptibility to its appearance and, additionally, prediction innovations regarding this disorder, which will certainly contribute to nursing care for patients with type 1 diabetes.La Diabetes Mellitus tipo 1 ha sido considerada una enfermedad autoinmune órgano-específica debido a la destrucción selectiva de las células beta pancreáticas. Presenta una patogenia compleja, involucrando la participación de varios factores, entre esos la susceptibilidad inmunogenética con fuerte asociación a los genes de histocompatibilidad (HLA), eventos ambientales y respuesta autoinmune con presencia de auto-anticuerpos y/o linfocitos auto-reactivos, culminando en anormalidades metabólicas. En este estudio, la revisión de la literatura describe los mecanismos por los cuales determinados factores resultan en susceptibilidad para su desarrollo y, adicionalmente, las innovaciones en la predicción de ese desorden que, por cierto, van a contribuir para la atención de enfermería a los pacientes portadores de la diabetes tipo 1.O diabetes mellitus do tipo 1 tem sido considerado uma doença auto-imune órgão-específica, decorrente da destruição seletiva das células betapancreáticas. Apresenta patogenia complexa, envolvendo a participação de vários fatores, dentre esses a susceptibilidade imunogenética com forte associação aos genes de histocompatibilidade (HLA), eventos ambientais e resposta auto-imune com presença de auto-anticorpos e/ou linfócitos auto-reativos, culminando em anormalidades metabólicas. Neste estudo, a revisão da literatura descreve os mecanismos pelos quais determinados fatores conferem susceptibilidade para o seu desencadeamento e, adicionalmente, as inovações na predição dessa desordem que, certamente, contribuirão para a assistência de enfermagem aos pacientes portadores do diabetes tipo 1

Differential Gene Expression Profiles May Differentiate Responder and Nonresponder Patients with Rheumatoid Arthritis for Methotrexate (MTX) Monotherapy and MTX plus Tumor Necrosis Factor Inhibitor Combined Therapy

Objective. We aimed to evaluate whether the differential gene expression profiles of patients with rheumatoid arthritis (RA) could distinguish responders from nonresponders to methotrexate (MTX) and, in the case of MTX nonresponders, responsiveness to MTX plus anti-tumor necrosis factor-alpha (anti-TNF) combined therapy. Methods. We evaluated 25 patients with RA taking MTX 15-20 mg/week as a monotherapy (8 responders and 17 nonresponders). All MTX nonresponders received intliximab and were reassessed after 20 weeks to evaluate their anti-TNF responsiveness using the European League Against Rheumatism response criteria. A differential gene expression analysis from peripheral blood mononuclear cells was performed in terms of hierarchical gene clustering, and an evaluation of differentially expressed genes was performed using the significance analysis of microarrays program. Results. Hierarchical gene expression clustering discriminated MTX responders from nonresponders, and MTX plus anti-TNF responders from nonresponders. The evaluation of only highly modulated genes (fold change > 1.3 or < 0.7) yielded 5 induced (4 antiapoptotic and CCL4) and 4 repressed (4 proapoptotic) genes in MTX nonresponders compared to responders. In MTX plus anti-TNF nonresponders, the CCL4, CD83, and BCL2A1 genes were induced in relation to responders. Conclusion. Study of the gene expression profiles of RA peripheral blood cells permitted differentiation of responders from nonresponders to MTX and anti-TNF. Several candidate genes in MTX non-responders (CCL4, HTRA2, PRKCD, BCL2A1, CAV1, TNIP1 CASP8AP2, MXD1, and BTG2) and 3 genes in MTX plus anti-TNF nonresponders (CCL4, CD83, and BCL2A1) were identified for further study. (First Release July 1 2012; J Rheumatol 2012;39:1524-32; doi:10.3899/jrheum.120092)Fundacao de Amparo a Pesquisa do Estado de Sao PauloFundacao de Apoio ao Ensino Pesquisa e Assistencia do HC, Faculdade de Medicina de Ribeirao Preto, USPConselho Nacional de Desenvolvimento Cientifico e Tecnologic

HPV type infection in different anogenital sites among HIV-positive Brazilian women

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Identifying common and specific microRNAs expressed in peripheral blood mononuclear cell of type 1, type 2, and gestational diabetes mellitus patients

Abstract\ud \ud \ud \ud Background\ud Regardless the regulatory function of microRNAs (miRNA), their differential expression pattern has been used to define miRNA signatures and to disclose disease biomarkers. To address the question of whether patients presenting the different types of diabetes mellitus could be distinguished on the basis of their miRNA and mRNA expression profiling, we obtained peripheral blood mononuclear cell (PBMC) RNAs from 7 type 1 (T1D), 7 type 2 (T2D), and 6 gestational diabetes (GDM) patients, which were hybridized to Agilent miRNA and mRNA microarrays. Data quantification and quality control were obtained using the Feature Extraction software, and data distribution was normalized using quantile function implemented in the Aroma light package. Differentially expressed miRNAs/mRNAs were identified using Rank products, comparing T1DxGDM, T2DxGDM and T1DxT2D. Hierarchical clustering was performed using the average linkage criterion with Pearson uncentered distance as metrics.\ud \ud \ud \ud Results\ud The use of the same microarrays platform permitted the identification of sets of shared or specific miRNAs/mRNA interaction for each type of diabetes. Nine miRNAs (hsa-miR-126, hsa-miR-1307, hsa-miR-142-3p, hsa-miR-142-5p, hsa-miR-144, hsa-miR-199a-5p, hsa-miR-27a, hsa-miR-29b, and hsa-miR-342-3p) were shared among T1D, T2D and GDM, and additional specific miRNAs were identified for T1D (20 miRNAs), T2D (14) and GDM (19) patients. ROC curves allowed the identification of specific and relevant (greater AUC values) miRNAs for each type of diabetes, including: i) hsa-miR-1274a, hsa-miR-1274b and hsa-let-7f for T1D; ii) hsa-miR-222, hsa-miR-30e and hsa-miR-140-3p for T2D, and iii) hsa-miR-181a and hsa-miR-1268 for GDM. Many of these miRNAs targeted mRNAs associated with diabetes pathogenesis.\ud \ud \ud \ud Conclusions\ud These results indicate that PBMC can be used as reporter cells to characterize the miRNA expression profiling disclosed by the different diabetes mellitus manifestations. Shared miRNAs may characterize diabetes as a metabolic and inflammatory disorder, whereas specific miRNAs may represent biological markers for each type of diabetes, deserving further attention.This study was funded by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP - (FAPESP #2008/56594-8, FAPESP #2010/05622-1, FAPESP #210/00932-2, FAPESP #2010/12069-7), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq # 563731/2010-9), and NAP-DIN (Núcleo de Apoio à Pesquisa em Doenças Inflamatórias)

Alterations in gene expression profiles correlated with cisplatin cytotoxicity in the glioma U343 cell line

Gliomas are the most common tumors in the central nervous system, the average survival time of patients with glioblastoma multiforme being about 1 year from diagnosis, in spite of harsh therapy. Aiming to study the transcriptional profiles displayed by glioma cells undergoing cisplatin treatment, gene expression analysis was performed by the cDNA microarray method. Cell survival and apoptosis induction following treatment were also evaluated. Drug concentrations of 12.5 to 300 μM caused a pronounced reduction in cell survival rates five days after treatment, whereas concentrations higher than 25 μM were effective in reducing the survival rates to ~1%. However, the maximum apoptosis frequency was 20.4% for 25 μM cisplatin in cells analyzed at 72 h, indicating that apoptosis is not the only kind of cell death induced by cisplatin. An analysis of gene expression revealed 67 significantly (FDR < 0.05) modulated genes: 29 of which down- and 38 up-regulated. These genes belong to several classes (metabolism, protein localization, cell proliferation, apoptosis, adhesion, stress response, cell cycle and DNA repair) that may represent several affected cell processes under the influence of cisplatin treatment. The expression pattern of three genes (RHOA, LIMK2 and TIMP2) was confirmed by the real time PCR method