Use of immune checkpoint inhibitors in the treatment of patients with cancer and preexisting autoimmune disease: An integrative review.

INTRODUCTION: Checkpoint inhibitors (PCI) have reached an important place in the pharmaceutical market in the treatment of various types of cancer. However, due to immune-related adverse events (IRAE) to the treatment, patients with preexisting autoimmune diseases (PAD) are excluded from clinical studies, leading to a large gap in knowledge on this topic. This study aims to discuss the use of PCI in the patients with cancer and PAD by an integrative review. METHODS: For this integrative review we carried out research from 2013 to 2022 using database platforms for observational studies reporting data from safety and efficacy of PCI in patients with cancer and PAD. RESULTS: The search resulted in 161 articles and after applying the exclusion criteria, 15 clinical studies that adopted a retrospective observational design were selected and analyzed. The age range of patients was 54-71 years, with 19-68% male. The proportion of patients clinically active or receiving immunosuppressants who were initiated on PCI ranged from 0% to 57% and 14% to 73%, respectively. The mean reported follow-up time ranged from 8.0 to 16.8 months. The occurrence of an outbreak or the new IRAE had an average of 32.6%. CONCLUSION: IRAE are frequent in patients who use PCI and have cancer and PAD, carrying discontinuation of therapy. However, the multidisciplinary team needs to be aligned to manage these situations in the best way.

Natural killer cell receptor and HLA-C gene polymorphisms among patients with hepatitis C: a comparison between sustained virological responders and non-responders.

BACKGROUND/AIMS: Killer cell immunoglobulin-like receptors (KIR) are involved in the activation/inhibition of NK cells through an interaction with HLA class I molecules on target cells. Our study aimed to evaluate the association between KIR gene polymorphisms and the response of patients with CHC to antiviral therapy. METHODS: We compared the frequency of KIR genes, as well as that of compound KIR/HLA-C genotypes, between groups of patients with CHC who presented a sustained virological response (n=66) and who were non-responders to a combination of pegylated or standard interferon and ribavirin (n=101). KIR and HLA-C genotyping were performed using commercial kits. RESULTS: We detected a greater frequency of the KIR2DL5 gene among non-responders to antiviral therapy compared with sustained virological responders (68.3 vs. 40.9%) (P<0.001). We used multiple logistic regression analysis to determine the association between therapy response and the presence of KIR2DL5, after a control for potentially confounding variables (genotype, alcohol, fibrosis, gender, age, ethnic background and route of HCV infection). The results confirmed the strong association between the presence of KIR2DL5 and the non-response to antiviral treatment (P=0.001). CONCLUSIONS: Host genetic factors may be associated with a non-response to antiviral therapy. KIR2DL5 is a candidate gene involved in immunomodulation associated with non-response to antiviral therapy.

Interferon-gamma release assay performance in northeastern Brazil: influence of the IFNG+874 A>T polymorphism.

INTRODUCTION: Latent tuberculosis infection diagnosis based on the release of interferon-gamma in cultures of peripheral blood cells stimulated with Mycobacterium tuberculosis antigens has replaced the tuberculin skin test in many countries with low tuberculosis prevalence. The IFN-γ production can be influenced by genetic polymorphisms, of which the IFNG+874 (rs62559044) locus is the most studied. We investigated the possible influence of the IFNG+874 A/T polymorphism on interferon-gamma test performance. METHODS: Patients diagnosed with pulmonary tuberculosis (75), volunteers with positive tuberculin skin test (70) and healthy volunteers with negative tuberculin skin test and no history of contact with tuberculosis (57) were evaluated regarding the IFNG+874 genotype and the IFN-γ levels in whole blood cultures performed using an interferon-gamma commercial kit (QuantiFERON-TB® Gold In-Tube). RESULTS: IFN-γ production was not influenced by the IFNG+874 genotype, regardless of antigen or mitogen-based stimulation, which suggests that other genes may influence IFN-γ production in response to mycobacteria. The IFNG+874 polymorphism was found to exert no influence over QFT-IT test sensitivity in our study. CONCLUSIONS: The IFNG+874 polymorphism was not shown to influence QuantiFERON-TB® Gold In-Tube test performance in an admixed population from northeastern Brazil.

Enterocolite Neutropênica em Paciente com Câncer de Mama em Uso de Quimioterapia Adjuvante: Relato de Caso / Neutropenic Enterocolitis in a Breast Cancer Patient using Adjuvant Chemotherapy: Case Report / Enterocolitis Neutropénica en Paciente con Cáncer de Mama que Usa Quimioterapia Adyuvante: Reporte de Caso

Introdução: A enterocolite neutropênica (EN) consiste em ulceração ou necrose da mucosa do ceco, íleo terminal e cólon ascendente, sendo uma condição clínica ocasionada como evento adverso de medicamentos, principalmente em esquemas quimioterápicos. Por ser uma condição com alto índice de mortalidade, o presente relato tem como objetivo contribuir significativamente para discussões que envolvem a EN e a participação da equipe multiprofissional no desfecho clínico. Relato do caso: Paciente do sexo masculino, 75 anos, com diagnóstico de câncer de mama, evoluindo com EN após tratamento com quimioterapia adjuvante. A presença de comorbidades e a idade foram os principais fatores complicadores do quadro de tiflite. Por ser uma toxicidade importante e que pode levar à piora do quadro clínico do paciente com câncer, abordar esse tema é fundamental para um diagnóstico mais rápido, com possibilidade de medidas preventivas. Conclusão: Sendo assim, em virtude do notório aumento dos casos de EN, aponta-se como perspectiva a qualificação da equipe de saúde para a inserção de profissionais ainda mais especializados, capazes de contribuir e identificar os sinais e sintomas relacionados com toxicidades hematológicas, resultado de tratamentos quimioterápicos.

Introduction: Neutropenic enterocolitis (NE) consists of ulceration or necrosis of the mucosa of the cecum, terminal ileum, and ascending colon, being a clinical condition caused by an adverse drug event, mainly in chemotherapy regimens. As it is a high mortality rate condition, this report aims to contribute significantly to discussions involving NE and the participation of the multidisciplinary team in the clinical outcome. Case report: This is a 75-year-old male patient diagnosed with Breast Cancer, who developed EN after treatment with adjuvant chemotherapy. The presence of comorbidities and age were the main complicating factors in typhlitis. As it is an important toxicity and can lead to a worsening of the clinical condition of cancer patients, addressing this issue is essential for a faster diagnosis with the possibility of preventive measures. Conclusion: Therefore, in view of the notorious increase of cases of NE, the perspective of the qualification of the health team is pointed out, for the inclusion of even more specialized professionals capable of contributing and identifying the signs and symptoms related to hematological toxicities, result of chemotherapy treatments.

Introducción: La enterocolitis neutropénica (EN) consiste en la ulceración o necrosis de la mucosa del ciego, íleon terminal y colon ascendente, siendo una condición clínica causada por un evento adverso farmacológico, principalmente en regímenes de quimioterapia. Al tratarse de una afección con una alta tasa de mortalidad, este informe tiene como objetivo contribuir de manera significativa a las discusiones que involucran al EN y la participación del equipo multidisciplinario en el resultado clínico. Relato del caso: Paciente masculino, 75 años, diagnosticado de cáncer de mama, que desarrolló EN después del tratamiento con quimioterapia adyuvante. La presencia de comorbilidades y la edad fueron los principales factores de complicación en Tiflite. Como se trata de una toxicidad importante y puede conducir a un empeoramiento de la condición clínica de los pacientes con cáncer, abordar esta cuestión es fundamental para un diagnóstico más rápido con la posibilidad de medidas preventivas. Conclusión: Por tanto, ante el notable incremento de casos de EN, se apunta la perspectiva de la calificación del equipo de salud, para la inclusión de profesionales aún más especializados capaces de aportar e identificar los signos y síntomas relacionados con las toxicidades hematológicas, un resultado de los tratamientos de quimioterapia.

Avaliação, Ensinagem e Metodologias Ativas: uma Experiência Vivenciada no Componente Curricular Mecanismos de Agressão e de Defesa, no curso de Medicina da Universidade do Estado da Bahia, Brasil / Evaluation, Teaching and Active Methodologies: an Experience as Part of the Curricular Component Mechanisms of Aggression and Defense of the Medicine course of Universidade do Estado da Bahia, Brazil

RESUMO A contemporaneidade e a docência nas áreas de saúde e formação profissional, tem se transformado e evoluído nos últimos tempos, com a introdução das metodologias ativas no processo ensino-aprendizagem, nas instituições de ensino superior no Brasil. Essas metodologias ativas de aprendizagem, como a ABP, Aprendizagem Baseada em Problemas, são utilizadas com a finalidade de que estudantes da área da saúde adquiram o conhecimento de forma significativa, em relação ao ensino tradicional. A educação médica no Brasil tem sido assunto de muitas discussões sobre a formação profissional em saúde e vem passando por significativas mudanças nos últimos anos. O presente artigo tem por objetivo relatar uma experiência docente no ensino de graduação em Medicina, nos componentes curriculares Mecanismo de Agressão e Defesa I e II (MADs), na Universidade do Estado da Bahia - Campus I. MADs é um componente curricular atualmente presente em diferentes cursos da área de saúde do Brasil. Este componente é composto pelas disciplinas microbiologia, parasitologia, imunologia e patologia, lecionado de forma integrada. Foram aplicadas metodologias ativas de ensino, do tipo aprendizagem baseada em problemas (ABP), que abrangeram sessões tutoriais, atividades em laboratórios, apresentações científicas e o uso de filmes. Além disto, foram utilizados recursos lúdicos e a ferramenta MOODLE no campus virtual. Esta proposta teve início no ano de 2012 e vem sendo aplicada a partir desta data até os dias atuais. A experiência vivenciada nas MADs, com a utilização de variadas formas de metodologias de ensinagem, tem permitido "romper" com o tradicional, isto é, tem levado o discente a desenvolver habilidades, competências e construção dos saberes. Estas novas alternativas de ensino nos permitiu uma interação mais ampla entre a relação discente-docente e nos fez refletir e avançar no processo avaliativo, que tem sido realizado de forma ampla e processual. Além disso, um impacto positivo para sua formação pode ser observado. No que se refere ao processo de ensino, aprendizagem e avaliações, novas propostas pedagógicas devem ser inseridas priorizando o caráter formativo e de desenvolvimento dos discentes, para que haja a construção de competências necessárias ao perfil estabelecido pelas DCNs, Diretrizes Curriculares Nacionais, do curso de Graduação em Medicina e demais cursos de saúde.

ABSTRACT Changes are occurring in health teaching and professional training, due to the introduction of active methodologies to the teaching-learning process in Brazilian higher education institutions. These active learning methodologies, such as PBL (Problem-Based Learning), are used to help medical students acquire knowledge in a more relevant way, compared to traditional teaching. Medical education in Brazil has been the subject of much discussion, and has undergone significant changes in recent years. The objective of the present work is to report the teaching experience in the curricular components Mechanisms of Aggression and Defense I (MAD I) and Mechanisms of Aggression and Defense II (MAD II) of Universidade do Estado da Bahia [State University of Bahia] - Campus I in undergraduate teaching in Medicine. These subjects are composed of the disciplines microbiology, parasitology, immunology (MAD I and II) and pathology (MAD II), taught in an integrated way. Active teaching methodologies were applied, such as problem-based learning, laboratory activities, scientific presentations and the use of film. In addition, the MOODLE tool was used in the virtual campus. This proposal began in 2012 and has been applied since then. The experience of the MADs, with the use of different forms of teaching methodologies, has led to a transformation of traditional teaching, leading students to develop their skills and competencies and build knowledge. These new teaching alternatives allow for a broader interaction between the students and the teacher and led us to reflect and advance in the evaluation process, which has been carried out in a broad and procedural way. Moreover, a positive impact on the students' training was observed. As for the processes of teaching, learning and evaluation, new pedagogical proposals should be introduced, prioritizing the formative and developmental character of students so that the necessary competences can be built into the profile established by the National Curricular Guidelines (DCNs) of the Undergraduate Medicine course and other courses in the area of health.

Farmacovigilância: terapia semi-intensiva da oncopediatria em um hospital filantrópico / Pharmacovigilance: semi-intensive oncopediatric therapy in a philanthropic hospital

Objetivo: analisar a utilização de medicamentos prescritos no setor de terapia semi-intensiva da oncopediatria em um hospital filantrópico, tendo em vista o desenvolvimento da farmacovigilância na prática farmacêutica. Métodos: foi realizada avaliação das prescrições médicas e pesquisa bibliográfica nas bases de dados sobre medicamentos no período de junho de 2015 a junho de 2016. As variáveis adotadas foram relacionadas às características sociodemográficas, clínicas, e os medicamentos prescritos foram classificados de acordo com a Anatomical Therapeutic Chemical Classification (ATC). Foram incluídas todas as prescrições oncológicas da unidade de terapia semi-intensiva, considerando a faixa etária de 0-18 anos, estratificada em 0-11 anos, 12-14 anos e 15-18 anos, no período de junho de 2015 a junho de 2016, excluindo aquelas que não atendiam aos requisitos. Os dados foram compilados no programa Statistical Package for the Social Sciences (SPSS), versão 22.0. Resultados: a maioria dos pacientes pertencia ao sexo masculino com prevalência na faixa etária entre 00-11 anos. A leucemia linfoide aguda foi o diagnóstico mais observado, e o desfecho de alta melhorada representou mais da metade da amostra. As classes terapêuticas mais prescritas corresponderam aos antineoplásicos, anti-infecciosos e aos que atuam no Sistema Nervoso Central (SNC). Conclusões: os resultados sugerem que o tratamento farmacológico, em unidade de terapia intensiva, envolve um grupo extenso de medicamentos, com predomínio de antineoplásicos, antibióticos e fármacos que atuam no SNC. É necessária atenção especial para a conduta terapêutica no atendimento à população pediátrica, visando minimizar, sobretudo, os eventos adversos inerentes ao tratamento oncológico.

Objective: ito analyze the use of drugs as prescribed in the semi-intensive therapy sector of oncopediatrics in a philanthropic hospital, in view of the development of pharmacovigilance in pharmaceutical practice. Methods: the evaluation of medical prescriptions and bibliographic research was carried out in the databases on drugs from June 2015 to June 2016. The variables adopted were related to sociodemographic, clinical characteristics and the prescribed drugs were classified according to the Anatomical Therapeutic Chemical Classification (ATC). All the oncological prescriptions of the semi-intensive therapy unit were included, considering the age range 0-18 years, stratified in 0-11 years, 12-14 years and 15-18 years, in the period from June 2015 to June of 2016, excluding those that did not meet the requirements. The data were compiled in the Statistical Package for the Social Sciences (SPSS), version 22.0. Results: most of the patients belonged to males with a prevalence in the age range between 00-11 years old. Acute lymphoblastic leukemia was the most observed diagnosis and the improved high endpoint accounted for more than half of the sample. The most prescribed therapeutic classes corresponded to: antineoplastic, anti-infectious and those acting on the Central Nervous System (CNS). Conclusions: the results suggest that pharmacological treatment in an intensive care unit involves an extensive group of drugs, with a predominance of antineoplastics, antibiotics and drugs acting in the CNS. Special attention is required for therapeutic management in the pediatric population, in order to minimize the adverse events inherent to cancer treatment.

Evolução da hemovigilância no Brasil: novas perspectivas de atuação do farmacêutico / Evolution of hemovigilance in Brazil: new prospects of pharmaceutical activities

A terapia transfusional é indicada como estratégia de manutenção ou reestabelecimento da homeostase. Similarmente ao que ocorre na administração de medicamentos ou produtos farmacêuticos, existe o risco de complicações ligadas à interação organismo-substância apesar da adoção de medidas preventivas. O reconhecimento das dimensões dos riscos associados à terapia transfusional demandam ação regulatória qualificada do Estado e presença de equipe técnica habilitada para monitoramento adequado. A pratica farmacêutica foi contemplada pela Resolução do Conselho Federal de Farmácia Nº617/2015, que estabelece atribuições clínicas ao farmacêutico na Hemoterapia, em adição a sua atuação já estabelecida nas Análises Clínicas. Objetivo: Este trabalho se propõe a realizar uma revisão da literatura sobre a atuação farmacêutica na Hemovigilância, discutindo suas novas atribuições. Material e métodos: Foi realizada uma revisão nas bases de dados MEDLINE/PUBMED, SCIENCE DIRECT, LILACS e SCIELO, no período de 2001 e 2018, em inglês, espanhol e português. Resultados: A partir da leitura dos artigos pôde-se constatar a necessidade de reorientação no escopo das práticas farmacêuticas na área da hemoterapia. É necessário organizar o trinômio "ensino- gestão - trabalho" para beneficiar os usuários dos sistemas de saúde. Adicionalmente, a discussão conjunta entre conselhos profissionais é importante para estabelecer limites de prática e o entendimento da responsabilidade compartilhada. Considerações finais: Este estudo ressalta a importância do Farmacêutico na equipe de saúde como profissional que desenvolve ações de promoção da saúde e segurança no cuidado do paciente na terapia transfusional.

Transfusion therapy is indicated to maintain and reestablish homeostasis. As in administration of drugs or pharmaceuticals, there is a risk of complications related to organism-substance interaction despite the adoption of preventive measures. Recognition of the risks' dimensions associated with transfusion therapy requires qualified regulatory action by the State and the technical team qualified for adequate monitoring. Therefore, a pharmaceutical practice was contemplated by the Resolution of the Federal Council of Pharmacy (CFF) Nº 617/2015, a qualification clinical assignments for the pharmacist in Hemotherapy. Objective: This paper proposes to carry out a systematic review of the literature on the pharmaceutical performance in Hemovigilance, discussing its new attributions. Material and methods: A review of the MEDLINE / PUBMED, SCIENCE DIRECT, LILACS and SCIELO databases was carried out in 2001 and 2018 in English, Spanish and Portuguese. Results: After the reading was possible to verify the necessity of reorientation in the pharmaceutical's scope practices in the hemotherapy area. It is necessary to organize the "teaching-management-work" trinomial to benefit users of health systems. In addition, joint discussion among professional councils is important in establishing limits of practice and understanding of shared responsibility. Final considerations: This review reintroduces that pharmacist is the professional who promotes safety in patient care in transfusion therapy.

Associação entre esclerose múltipla e alelos HLA-DRB1 em uma população miscigenada de Salvador, Ba, Brasil / Association between multiple sclerosis and HLA-DRB1 alleles in an admixed population of Salvador, Ba, Brazil

Introdução: a esclerose múltipla é uma doença que afeta preferencialmente o sistema nervoso central de mulheres jovens, causandolhes graus variáveis de incapacidades física e cognitiva. Etiologicamente associa fatores ambientais, biológicos, sócio-econômicos e genéticos, como por exemplo genes do MHC classe II, especialmente os alelos HLA-DRB1*. Objetivo: determinar a frequência dos alelos HLA DRB1* em portadores de esclerose múltipla atendidos no centro de referência do C.H.U.P.E.S, UFBA, no período de outubro de 2014 a abril de 2015 e associá-las a variáveis clínico-demográficas. Metodologia: estudo do tipo caso-controle, aprovado pelo comitê de ética da Faculdade de medicina da Universidade Federal da Bahia (CAAE: 3517134.0.0000.5577), que envolveu uma amostra de conveniência composta por 97 indivíduos, cujos dados clínico-demográficos foram coletados através de questionário desenvolvido para a pesquisa. A genotipagem dos alelos HLA-DRB1* foi realizada através da técnica HLA-DR SSO GenotypingTest. Resultados: a análise quantitativa revelou perfil genotípico do tipo HLA-DRB1*15 (20,5%), em mulheres (83,0%), das raças/etnias negra ou parda (75,0%), com faixa etária entre 30 e 39 anos (28,0%). Houve predomínio da forma clínica surtoremissiva da doença (76,0%), dentre os doentes com idade mais avançada (55,0%), sem permanência de sequela clínica (70,0%) e que usavam algum tipo de Interferon (58,0%). A análise qualitativa indicou maiores frequências, na forma progressiva de esclerose múltipla dos grupos alélicos HLA-DRB1*12 (22,0%), e dos alelos HLA-DRB1*13 (12,6%)e HLA-DRB1*15 (22,0%) naqueles indivíduos com a forma surtoremissiva. Negros e pardos demonstraram maior prevalência do alelo HLA-DRB1*15 (24,0%), enquanto que nos brancos houve maior prevalência do alelo HLA-DRB1*07 (20,0%). Conclusão: forte associação entre as frequências alélicas, esclerose múltipla e as variáveis raça/etnia e forma clínica da doença.

Polymorphisms of the cytokine genes TGFB1 and IL10 in a mixed-race population with Crohn's disease.

BACKGROUND: Most Crohn's disease (CD) genes discovered in recent years are associated with biological systems critical to the development of this disease. TGFB1 and IL10 are cytokines with important roles in CD. The aim of this study was to evaluate the association between CD, its clinical features and TGFB1 and IL10 gene polymorphisms. METHODS: This case-control study enrolled 91 patients and 91 controls from the state of Bahia, Brazil. Five single nucleotide polymorphisms (SNPs) were studied in the TGFB1 gene (codon 10 T > C--rs1800470; codon 25 G > C--rs1800471) and IL10 gene (-1082 A > G--rs1800896; -819 T > C--rs1800871; -592 A > C--rs1800872). An analysis of the genetic polymorphisms was performed using a commercial kit. A comparison of allele frequencies and genotypes was estimated by calculating the odds ratio (OR) with a confidence interval adjusted via the Bonferroni test for a local alpha of 1%. A stratified analysis was applied for gender, race and smoking history. Patients with CD were characterized according to the Montreal classification. RESULTS: The C allele and CC genotype of the TGFB1 gene rs1800470 were both significantly associated with CD. The stratified analysis showed no confounding factors for the co-variables of gender, race and smoking history. The IL10 gene rs1800896 G allele was significantly associated with age at diagnosis of CD, while the T allele of the IL10 gene rs1800871 was significantly associated with perianal disease. The SNPs rs1800871 and rs1800872 were in 100% linkage disequilibrium. CONCLUSIONS: TGFB1 gene polymorphisms may be associated with susceptibility to the development of CD, and IL10 gene polymorphisms appear to influence the CD phenotype in this admixed population.

Interferon-gamma release assay performance in northeastern Brazil: influence of the IFNG+874 A>T polymorphism

ABSTRACT Introduction Latent tuberculosis infection diagnosis based on the release of interferon-gamma in cultures of peripheral blood cells stimulated with Mycobacterium tuberculosis antigens has replaced the tuberculin skin test in many countries with low tuberculosis prevalence. The IFN-γ production can be influenced by genetic polymorphisms, of which the IFNG + 874 (rs62559044) locus is the most studied. We investigated the possible influence of the IFNG + 874 A/T polymorphism on interferon-gamma test performance. Methods Patients diagnosed with pulmonary tuberculosis (75), volunteers with positive tuberculin skin test (70) and healthy volunteers with negative tuberculin skin test and no history of contact with tuberculosis (57) were evaluated regarding the IFNG + 874 genotype and the IFN-γ levels in whole blood cultures performed using an interferon-gamma commercial kit (QuantiFERON-TB® Gold In-Tube). Results IFN-γ production was not influenced by the IFNG + 874 genotype, regardless of antigen or mitogen-based stimulation, which suggests that other genes may influence IFN-γ production in response to mycobacteria. The IFNG + 874 polymorphism was found to exert no influence over QFT-IT test sensitivity in our study. Conclusions The IFNG + 874 polymorphism was not shown to influence QuantiFERON-TB® Gold In-Tube test performance in an admixed population from northeastern Brazil.

Porphyromonas gingivalis HmuY-induced production of interleukin-6 and IL-6 polymorphism in chronic periodontitis.

BACKGROUND: In chronic periodontitis (CP), the gene polymorphism of interleukin-6 (IL-6) to 174C/G has been associated with the altered production of this cytokine. The aim of this pilot study is to compare the allelic and genotypic frequencies in patients with CP with control individuals without periodontitis (NP) and to measure the production of IL-6 by whole blood cells stimulated with Porphyromonas gingivalis HmuY protein. METHODS: DNA was isolated from peripheral blood cells of 49 patients with CP and 60 control individuals classified as NP, and genotyping was performed by polymerase chain reaction using sequence-specific primers. Whole blood cells from 29 patients with CP and 30 control individuals were stimulated for 48 hours with HmuY, and IL-6 levels were measured using enzyme-linked immunosorbent assay. RESULTS: The proportion of individuals carrying the G allele at position -174 of the IL-6 gene was higher in the group with CP (85.7%) than in the normal control group (73.3%; P <0.03). P. gingivalis HmuY-induced production of IL-6 was higher in the group with CP (P <0.05). CONCLUSIONS: Our findings suggest that P. gingivalis HmuY may be associated with increased IL-6 production during CP. Furthermore, patients with periodontitis and individuals with higher HmuY-induced production of IL-6 show a high frequency of the G allele at position -174.

The TNF-α -308 polymorphism may affect the severity of Crohn's disease.

OBJECTIVE: The goal of this project was to analyze the association between Crohn's disease, its clinical features, and the tumor necrosis factor alpha (TNF-α) -308 polymorphism. METHODS: This is a case-control and cross-sectional study that enrolled 91 patients with Crohn's disease and 91 controls. Patients with Crohn's disease were characterized according to the Montreal Classification, along with their clinical and surgical treatment history. Analysis of the TNF-α -308 polymorphism was performed using a commercial kit. A stratified analysis was applied using an OR (odds ratio) with a 95% confidence interval. The chi-square and Fisher's exact tests were utilized for analysis of the association between the polymorphism and the clinical features of Crohn's disease. RESULTS: The low producer predicted phenotype was present in 76.9% of Crohn's disease cases and 75.8% of controls (OR 0.94 [0.45-1.97]). The TNF2 allele and the high producer predicted phenotype were more frequent among patients with Crohn's disease penetrating behavior (p = 0.004). The TNF2 allele and the high producer predicted phenotype were also associated with a history of colectomy (p = 0.02), and the TNF2 allele was associated with small bowel resection (p = 0.03). CONCLUSIONS: The TNF-α -308 polymorphism appears to affect the severity of the disease. However, TNF-α -308 polymorphism does not appear to be important for the susceptibility in the development of Crohn's disease.

HLA-Bw4-B*57 and Cw*18 alleles are associated with plasma viral load modulation in HIV-1 infected individuals in Salvador, Brazil.

UNLABELLED: Host genetic factors play an important role in mediating resistance to HIV-1 infection and may modify the course of infection. HLA-B alleles (Bw4 epitope; B*27 and B*57) as well as killer cell immunoglobulin-like receptors have been associated with slow progression of HIV-1 infection. OBJECTIVE: To evaluate the association between serological epitopes HLA-Bw4 and HLA-Bw6 and prognostic markers in AIDS. METHODS: 147 HIV-infected individuals in Bahia, Northeast Brazil, were genotyped for HLA class I locus. HLA class I genotyping was performed by hybridization with sequence-specific oligonucleotide probes following amplification of the corresponding HLA-A, HLA-B and HLA-C genes. Statistical analysis was performed using Fisher's exact and ANOVA tests for categorical and continuous variables, respectively. RESULTS: We detected a significant association (χ2 = 4.856; p = 0.018) between the presence of HLA-Bw4 and low levels of viremia. Eighteen out of the 147 HIV-infected individuals presented viremia <1,800 copies/mL and 129 presented viremia > 2,000 copies/mL. Ninety and four percent (17/18) of all individuals with viremia < 1,800 copies/mL carried HLA-Bw4, compared to 67.4% (87/129) of individuals with viremia > 2,000 copies/mL. Additionally, we found a significantly higher frequency of B*57 (OR = 13.94; 95% CI = 4.19-46.38; p < 0.0001) and Cw*18 (OR = 16.15; 95% CI = 3.46-75.43; p < 0.0001) alleles, favoring the group with lower viremia levels, in comparison with those with higher viral load. CONCLUSION: HLA-Bw4-B*57 and Cw*18 alleles are associated with lower level of viral load in HIV-infected Brazilian patients. These findings may help us in understanding the determinants of HIV evolution in Brazilian patients, as well as in providing important information on immune response correlates of protection for such population.

The TNF-α -308 polymorphism may affect the severity of Crohn's disease

OBJECTIVE: The goal of this project was to analyze the association between Crohn's disease, its clinical features, and the tumor necrosis factor alpha (TNF-α) -308 polymorphism. METHODS: This is a case-control and cross-sectional study that enrolled 91 patients with Crohn's disease and 91 controls. Patients with Crohn's disease were characterized according to the Montreal Classification, along with their clinical and surgical treatment history. Analysis of the TNF-α -308 polymorphism was performed using a commercial kit. A stratified analysis was applied using an OR (odds ratio) with a 95 percent confidence interval. The chi-square and Fisher's exact tests were utilized for analysis of the association between the polymorphism and the clinical features of Crohn's disease. RESULTS: The low producer predicted phenotype was present in 76.9 percent of Crohn's disease cases and 75.8 percent of controls (OR 0.94 [0.45-1.97]). The TNF2 allele and the high producer predicted phenotype were more frequent among patients with Crohn's disease penetrating behavior (p = 0.004). The TNF2 allele and the high producer predicted phenotype were also associated with a history of colectomy (p = 0.02), and the TNF2 allele was associated with small bowel resection (p = 0.03). CONCLUSIONS: The TNF-α -308 polymorphism appears to affect the severity of the disease. However, TNF-α -308 polymorphism does not appear to be important for the susceptibility in the development of Crohn's disease.

Polymorphism of cytokine genes (TGF-beta1, IFN-gamma, IL-6, IL-10, and TNF-alpha) in patients with chronic pancreatitis.

OBJECTIVES: The polymorphisms in cytokine genes have allowed for the understanding of the genetic determinants of diseases. The aims of this study were to describe and compare the frequencies of polymorphisms on the interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta1, and interferon (IFN)-gamma genes between patients with chronic pancreatitis (CP) and healthy individuals from Bahia, Brazil. METHODS: Twenty-eight individuals were evaluated at a university gastroenterology outpatient service (4 women and 24 men), all diagnosed with CP based on clinical and radiologic aspects. The control group was composed of 94 (11 women and 83 men) blood donors. The polymorphisms studied were TNF-alpha (-308G/A), TGF-beta1 (codon 10C/T, codon 25C/G), IL-10 (-1082A/G; -819T/C; -592A/C), IL-6 (-174G/C), and IFN-gamma (+874T/A). RESULTS: A statistically significant difference was observed in the frequency of the polymorphisms between the group of patients with CP and the group of healthy individuals with the polymorphism of the TGF-beta1 gene on codon 10. No statistically significant differences were found for the allele and genotypic frequencies on the genes that code TNF-alpha, IFN-gamma, IL-10, and TGF-beta1 codon 25, and IL-6 between the control and case groups. CONCLUSION: The genotypes corresponding to the high TGF-beta1 producer phenotypes can be associated with the fibrogenesis shown with CP.

HLA-Bw4-B*57 and Cw*18 alleles are associated with plasma viral load modulation in HIV-1 infected individuals in Salvador, Brazil

Host genetic factors play an important role in mediating resistance to HIV-1 infection and may modify the course of infection. HLA-B alleles (Bw4 epitope; B*27 and B*57) as well as killer cell immunoglobulin-like receptors have been associated with slow progression of HIV-1 infection. OBJECTIVE: To evaluate the association between serological epitopes HLA-Bw4 and HLA-Bw6 and prognostic markers in AIDS. METHODS: 147 HIV-infected individuals in Bahia, Northeast Brazil, were genotyped for HLA class I locus. HLA class I genotyping was performed by hybridization with sequence-specific oligonucleotide probes following amplification of the corresponding HLA-A, HLA-B and HLA-C genes. Statistical analysis was performed using Fisher's exact and ANOVA tests for categorical and continuous variables, respectively. RESULTS: We detected a significant association (χ2 = 4.856; p = 0.018) between the presence of HLA-Bw4 and low levels of viremia. Eighteen out of the 147 HIV-infected individuals presented viremia <1,800 copies/mL and 129 presented viremia > 2,000 copies/mL. Ninety and four percent (17/18) of all individuals with viremia < 1,800 copies/mL carried HLA-Bw4, compared to 67.4 percent (87/129) of individuals with viremia > 2,000 copies/mL. Additionally, we found a significantly higher frequency of B*57 (OR = 13.94; 95 percent CI = 4.19-46.38; p < 0.0001) and Cw*18 (OR = 16.15; 95 percent CI = 3.46-75.43; p < 0.0001) alleles, favoring the group with lower viremia levels, in comparison with those with higher viral load. CONCLUSION: HLA-Bw4-B*57 and Cw*18 alleles are associated with lower level of viral load in HIV-infected Brazilian patients. These findings may help us in understanding the determinants of HIV evolution in Brazilian patients, as well as in providing important information on immune response correlates of protection for such population.

Citocinas e imunomodulação: novos avanços no tratamento das pancreatites / Cytokines and immunomodulation: new targets for pancreatitis treatment

As pancreatites se caracterizam por intenso processo inflamatório. A ativação de citocinas determina ou modula os principais mecanismos de lesão tissular local e à distância, participando dos danos que caracterizam as formas agudas ou crônicas de pancreatite. O trabalho faz uma revisão dos aspectos referentes à participação das citocinas na fisiopatologia das pancreatites, descrevendo de forma crítica as abordagens metodológicas que permitiram o seu estudo e apontando as novas modalidades de tratamento, com base na imunomodulação das citocinas.