Luciana Conci Macedo

Association of cytokine genetic polymorphisms with the humoral immune response to recombinant vaccine against HBV in infants

The prevention of hepatitis B by vaccination is one the most efficient tools to avoid the transmission of the virus, although a considerable variability to the anti‐HBsAg antibody response has been described. Recently, polymorphisms of cytokine regulating genes have been described which seem to influence the immune response to various antigens. This articles objective was to evaluate the influence of cytokine genetic polymorphisms onto the humoral immune response to hepatitis B vaccine in infants. Vaccinated children were classified according to the level of anti‐HBsAg antibody titles. The genotyping for TNF (−308), TGFB1 (+869, +915), IL‐10 (−1082, −819, −592), IL‐6 (−174), and IFNG (+874) was accomplished by the PCR‐SSP technique. The TNF (−308) allele A presented a lower but not statistically significant frequency at 5% level in high responder patients (3.7% vs. 12.3%, P = 0.0919). The same was seen for the TNF (−308) genotype GA (7.4% vs. 24.5%, P = 0.0757). Further studies in other populations and evaluation of a greater number of individuals may contribute for a better understanding of the cytokine gene polymorphism influence in general and TNF polymorphism more specifically in the humoral immune response to the HBsAg vaccination in newborn children. J. Med. Virol. 82:929–933, 2010.

New associations: INFG and TGFB1 genes and the inhibitor development in severe haemophilia A

The development of factor VIII (FVIII) inhibitor is the main complication of replacement therapy in patients with haemophilia A (HA). A ratio of 5–7% of individuals HA develops antibodies (inhibitors) against the FVIII infused during the treatment, thereby reducing their pro‐coagulant activity. The immunomodulatory cytokine genes have been related to the risk of development of alloantibodies in several studies, mainly in HA with severe form.

Genetics factors associated with myelodysplastic syndromes.

The myelodysplastic syndromes (MDS) are a clinically and cytogenetically heterogeneous group of clonal diseases. Clonal chromosomal abnormalities are observed in 30-50% of patients with MDS. The deletions are among the most common alterations, and often involve the long arms of chromosomes 5, 7, 8, 13, and 20 and the short arms of chromosomes 12 and 17. The advent of new technologies for the detection of genetic abnormalities led to the description of a new set of recurrent mutations, leading to new insights into the pathophysiology of MDS. The recent recognition that genes involved in the regulation of histone function (EZH2, ASXL1, and UTX) and DNA methylation (DNMT3A, IDH1/IDH2, and TET2) are frequently mutated in MDS, has led to the proposal that there is an important link between genetic and epigenetic alterations in this disease. In fact, regulatory factors have also been considered as miR-143/miR-145, miR-146a, miR-125a and MiR-21. Somatic mutations may influence the clinical phenotype but are not included in current prognostic scoring systems. In recent years research has brought new insights into these diseases, but few of the findings are sufficiently robust to be incorporated into the clinical routine at this time. Thus, the aim of this study was to review the role of genetic factors involved in the diagnosis and development of the different phenotypes of MDS.

Polifarmácia em Idosos

According to WHO, mental health does not merely comprise mental disturbances but also defines it as the well-being and potential of individuals in being capable of dealing with normal day-to-day stress and its influence on productivity in themselves and in their community. Current investigation, a transversal analysis with a quantitative-analytic focus, identifies the activities of nurses of the Family Help Strategy (ESF) with people with mental disturbances. Study was undertaken in ten Basic Health Units (UBS) in the municipality of Maringa PR Brazil. A self-applicable questionnaire was undertaken for data collection, with ten closed questioned. Subjects were 33 nurses working at the ESF of whom 31 (94%) were females and 2 (6%) were males, aged between 25 and 54 years old. Service time varied accordingly, or rather, 19 (58%) worked between five and ten years; 9 (27%) worked less than five years; 4 (12%) worked between 10 to 15 years; only 1 (3%) worked for more than 15 years. It should be highlighted than 23 (70%) nurses who worked for ESF did not have any experience in dealing with patients with mental disturbances, while 10 (30%) already had. Data showed that the most frequent activities were home visits and introduction undertaken by 32 (97%) nurses. ESF proposes changes in the links between the current assistance model and the patients coupled to the organization of presentation and realization in health promotion.The quality of inside air in closed places is affected by several conditions such as premise structure, external environment, occupants´ habits and activities developed there. Pollution by micro-organisms, such as bacteria and fungi, may trigger the development of allergies, respiratory problems and other immunological reactions. It may be considered as one of the main environmental and public health problems. The concentration of fungi and bacteria in an agricultural-industrial firm in the central-western region of the state of Parana, Brazil, is quantified to verify internal air pollution through basic parameters established by the National Agency for Sanitary Vigilance (ANVISA). Samples were collected by sedimentation methods in Petri plates during August and September 2012 during working hours, with the air-conditioning running on. Microbiological quality of the external air was also undertaken to compare inside and outside air. Concentrations of fungi and bacteria complied with limits permitted by Brazilian law (I/E < 1.5). It may be said that the internal air was of good quality with regard to concentrations of micro-organisms.

Importance of immune response genes in hemophilia A

Hemophilia A is a disease caused by a deficiency of coagulation factor VIII resulting from genetic inheritance linked to chromosome X. One treatment option is the administration of plasma or recombinant FVIII. However, some patients develop inhibitors or antibodies against this factor. Inhibitors are alloantibodies that bind to the epitope of factor VIII causing it to be recognized by the immune system as a foreign peptide. This is the most serious complication in hemophilia patients in respect to replacement therapy. Some studies have suggested that genetic factors influence the development of factor VIII inhibitors such as ethnicity, family history, mutations in the factor VIII gene and in genes of the immune system. The aim of this study was to conduct a literature review to assess the influence of genetic factors of immune response genes, especially genes of the major histocompatibility complex and cytokines, which may be related to the development of factor VIII inhibitors in hemophilia A patients. Understanding these risk factors will help to determine future differential treatment in the control and prevention of the development of inhibitors.

HLA polymorphisms and risk of red blood cell alloimmunisation in polytransfused patients with sickle cell anaemia

Red blood cell (RBC) alloimmunisation is an event that may occur due to factors such as numerous blood transfusions, age, gender and genetic factors such as human leukocyte antigen (HLA).

Letter to the Editor Concerning: The Role of Human Leukocyte Antigen Typingin Libyan Patients with Chronic Periodontitis

According to the article written by Daeki et al. [1] published in this journal, the authors of the manuscript investigated possible relationships between HLA and chronic periodontitis in Libyan patients and concluded that some HLA class I may represent risk factors and one class II allele group and the HLA-DRB5 loci may indicate protective factors for disease. This is an important study because the correlation between genetic marker with oral diseases could be influenced by geographical diversity in populations. However, we have concerns about the HLA and about a citation in the article published by our research group (Probst et al. [2]).

Genetic Polymorphisms of IL17 and Chagas Disease in the South and Southeast of Brazil

The aim of this study was to investigate possible associations between genetic polymorphisms of IL17A G197A (rs2275913) and IL17F T7488C (rs763780) with Chagas Disease (CD) and/or the severity of left ventricular systolic dysfunction (LVSD) in patients with chronic Chagas cardiomyopathy (CCC). The study with 260 patients and 150 controls was conducted in the South and Southeast regions of Brazil. The genotyping was performed by PCR-RFLP. The A allele and A/A genotype of IL17A were significantly increased in patients and their subgroups (patients with CCC; patients with CCC and LVSD; and patients with CCC and severe LVSD) when compared to the control group. The analysis according to the gender showed that the A/A genotype of IL17A was more frequent in female with LVSD and mild to moderate LVSD and also in male patients with LVSD. The frequency of IL17F T/C genotype was higher in male patients with CCC and severe LVSD and in female with mild to moderate LVSD. The results suggest the possible involvement of the polymorphisms of IL17A and IL17F in the susceptibility to chronic Chagas disease and in development and progression of cardiomyopathy.

Association of TNF polymorphisms with JAK2 (V617F) myeloproliferative neoplasms in Brazilian patients

The classical chromosome Philadelphia-negative myeloproliferative neoplasms (MPNs) are a group of disorders that share clinical, hematological, and histological features. Proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) are elevated in patients with MPN. The aim of this study was to verify the association between the polymorphisms of TNF gene (-308G/A and -238 G/A) in BCR-ABL-negative MPN in our population. Blood samples obtained from MPN patients were genotyped for the JAK2V617F mutation and both TNF polymorphisms using PCR-RFLP. Thirty three (26.8%) patients with polycythemia vera (PV), 35 (28.7%) essential thrombocythemia (ET), 22 (17.7%) primary myelofibrosis (PMF), and 33 (26.8%) with unclassifiable MPN (MPNu) were included in the study. The JAK2 V617F mutation was detected in 94 (76.42%) patients. Were observed a significant increase on the frequency of the TNF-238 GA genotype in MPN patients compared to controls (OR=2.21, 95% CI=1.02-4.80, P<0.04). The distribution of the genotypes and allelic frequencies of TNF-308 was significantly different among the MPNs, JAK2V617F positive, PV and PMF, and controls. Our data has demonstrated that the polymorphisms on TNF-238 GA, TNF-308 GA were associated to MPN development in this population, triggered by JAK2 V617F mutation.

Allele and haplotype frequencies of HLA-A, B, C, DRB1 and DQB1 genes in polytransfused patients in ethnically diverse populations from Brazil.

The red blood transfusion is a practice often used in patients with haematological and oncological diseases. However, the investigation of human leucocyte antigen (HLA) system frequency in these individuals is of great importance because multiple transfusions may lead to HLA alloimmunization. Brazil is a country that was colonized by many other ethnicities, leading to a mixed ethnicity and regionalized population. In view of the importance of HLA typing in these patients, the aim of this study was to investigate the allele and haplotype frequencies from polytransfused patients from three different regions from Brazil. HLA‐A, HLA‐B, HLA‐C, HLA‐DRB1 and HLA‐DQB1 genotyping of 366 patients was performed by PCR‐SSO, based on the Luminex technology (One Lambda®), and the anti‐HLA class I and class II antibodies were analysed using LabScreen Single Antigen Antibody Detection (One Lambda, Inc.). Allele and haplotype frequencies of polytransfused patients of three regions from Brazil were obtained using the Arlequin program. The most frequent allele frequencies observed were HLA‐A*02, A*03, B*15, B*35, B*51, C*07, C*04, C*03, DRB1*13, DRB1*11, DRB1*07, DRB1*03, DRB1*01, DQB1*03, DQB1*02, DQB1*06 and DQB1*05. There were differences between the groups for allele variants HLA‐B*57 (between Group 1 and Group 2) and HLA‐C*12 (between Group 1 and Group 3). The most frequent haplotypes found in the sample were HLA‐A*01B*08DRB1*03, DRBI*07DQB1*02, DRB1*01DQB1*05, DRB1*13DQB1*06 and A*02B*35. HLA class I and II antibodies were detected in 77.9% and 63.9% patients, respectively, while the both alloantibodies were detected in 62 (50.9%) patients. In conclusion, the HLA typing for polytransfused patients in each region has a great importance, as seen in this study; individuals from different regions from Brazil have HLA distribution not completely homogeneous.