Performances of HTLV serological tests in diagnosing HTLV infection in high-risk population of São Paulo, Brazil Desempenho de testes sorológicos para o diagnóstico de infecção por HTLV em população de alto-risco de São Paulo, Brasil

Testing problems in diagnosing human T-lymphotropic virus (HTLV) infection, mostly HTLV-II, have been documented in HIV/AIDS patients. Since December 1998, the Immunology Department of Instituto Adolfo Lutz (IAL) offers HTLV-I/II serology to Public Health Units that attend HTLV high-risk individuals. Two thousand, three hundred and twelve serum samples: 1,393 from AIDS Reference Centers (Group I), and 919 from HTLV out-patient clinics (Group II) were sent to IAL for HTLV-I/II antibodies detection. The majority of them were screened by two enzyme immunoassays (EIAs), and confirmed by Western Blot (WB 2.4, Genelabs). Seven different EIA kits were employed during the period, and according to WB results, the best performance was obtained by EIAs that contain HTLV-I and HTLV-II viral lysates and rgp21 as antigens. Neither 1st and 2nd, nor 3rd generation EIA kits were 100% sensitive in detecting truly HTLV-I/II reactive samples. HTLV-I and HTLV-II prevalence rates of 3.3% and 2.5% were detected in Group I, and of 9.6% and 3.6% in Group II, respectively. High percentages of HTLV-seroindeterminate WB sera were detected in both Groups. The algorithm testing to be employed in HTLV high-risk population from São Paulo, Brazil, needs the use of two EIA kits of different formats and compounds as screening, and because of high seroindeterminate WB, may be another confirmatory assay.<br>Problemas nos testes diagnósticos de infecção pelos vírus linfotrópicos de células T humanas (HTLV), principalmente HTLV-II, têm sido observados em pacientes com HIV/Aids. Desde Dezembro de 1998, a Seção de Imunologia do Instituto Adolfo Lutz (IAL) oferece a sorologia para HTLV-I/II para Serviços de Saúde Pública que atendem populações consideradas de risco para esta infecção. Duas mil trezentas e doze amostras de soro: 1.393 de Centros de Referência em Aids (Grupo I) e 919 de Clínicas de Especialidade em HTLV (Grupo II) foram encaminhadas para o IAL para a pesquisa de anticorpos anti-HTLV-I/II. A maioria delas foram testadas por dois ensaios imunoenzimáticos (EIAs) e confirmadas por Western Blot (WB 2.4, Genelabs). Sete kits diferentes de EIAs foram empregados durante o período e de acordo com os resultados do WB a melhor performance foi obtida com os EIAs que continham lisado viral dos HTLV-I e -II e a rgp21 como antígenos. Nenhum kit de EIA de 1ª, 2ª ou 3ª geração foi 100% sensível para detectar todas as amostras verdadeiramente HTLV-I/II reagentes. A prevalência de HTLV-I e HTLV-II, respectivamente, foi de 3,3% e 2,5% no Grupo I e de 9,6% e 3,6% no Grupo II. Em ambos os Grupos, foram detectadas altas percentagens de soros com padrão indeterminado no WB. O algoritmo de testes sorológicos para ser usado em população de alto risco para HTLV de São Paulo, Brasil, necessita de dois kits EIAs de princípios e composição diferentes para a triagem sorológica e, pelo elevado número de WB indeterminado, talvez de um outro teste confirmatório

Socio-demographic and epidemiological characteristics associated with human immunodeficiency virus type I (HIV-1) infection in HIV-1-explosed but uninfected individuals, and in HIV-1-infected patients from a southern brasilian population Características sociodemográficas e epidemiológicas associadas com a infecção pelo vírus da imunodeficiência humana tipo 1 (HIV-1) em indivíduos expostos ao HIV-1 mas não infectados e em pacientes infectados pelo HIV-1, provenientes da população da região Sul do Brasil

The ability to control human immunodeficiency virus type 1 (HIV-1) infection and progression of the disease is regulated by host and viral factors. This cross-sectional study describes the socio-demographic and epidemiological characteristics associated with HIV-1 infection in 1,061 subjects attended in Londrina and region, south of Brazil: 136 healthy individuals (Group 1), 147 HIV-1-exposed but uninfected individuals (Group 2), 161 HIV-1-infected asymptomatic patients (Group 3), and 617 patients with AIDS (Group 4). Data were obtained by a standardized questionnaire and serological tests. The age of the individuals ranged from 15.1 to 79.5 years, 54.0% and 56.1% of the Groups 3 and 4 patients, respectively, were men. The major features of groups 2, 3, and 4 were a predominance of education level up to secondary school (55.8%, 60.2% and 62.4%, respectively), sexual route of exposure (88.4%, 87.0% and 82.0%, respectively), heterosexual behavior (91.8%, 75.2% and 83.7%, respectively), and previous sexually transmitted diseases (20.4%, 32.5%, and 38.1%, respectively). The patients with AIDS showed the highest rates of seropositivity for syphilis (25.6%), of anti-HCV (22.3%), and anti-HTLV I/II obtained by two serological screening tests (6.2% and 6.8%, respectively). The results documenting the predominant characteristics for HIV-1 infection among residents of Londrina and region, could be useful for the improvement of current HIV-1 prevention, monitoring and therapeutic programs targeted at this population.<br>Este estudo transversal descreve as principais características sociodemográficas e epidemiológicas associadas com a infecção pelo HIV-1 em 1.061 indivíduos atendidos em Londrina e região, Sul do Brasil: 136 indivíduos saudáveis (Grupo 1), 147 indivíduos expostos ao HIV-1 mas não infectados (Grupo 2), 161 pacientes infectados pelo HIV-1 assintomáticos (Grupo 3) e 617 pacientes com aids (Grupo 4). Os dados foram obtidos pela aplicação de um questionário padronizado e realização de testes sorológicos. A idade dos indivíduos variou de 15,1 a 79,5 anos; 54,0% e 56,1% dos pacientes dos Grupos 3 e 4, respectivamente, eram homens. As principais características dos indivíduos dos Grupos 2, 3 e 4 foram o predomínio do nível educacional com até oito anos de escolaridade (58,8%, 60,2% e 62,4%, respectivamente), a via sexual de transmissão (88,4%, 87,0% e 82,0%, respectivamente), o comportamento heterossexual (91,8%, 75,2% e 83,7%, respectivamente) e antecedentes de doenças sexualmente transmissíveis (20,4%, 32,5% e 38,1%, respectivamente). Os pacientes com aids apresentaram os valores mais elevados de soropositividade para sífilis (25,6%), anti-HCV (22,3%) e anti-HTLV I/II em dois testes de triagem sorológica (6,2% e 6,8%, respectivamente). Os resultados documentando as características predominantes associadas com a infecção pelo HIV-1 observada nos indivíduos de Londrina e região, poderá ser útil na melhoria dos atuais programas de prevenção, monitoramento e de tratamento da infecção pelo HIV-1 dirigidos a esta população

Penetrance of biallelic SMARCAL1 mutations is associated with environmental and genetic disturbances of gene expression

Biallelic mutations of the DNA annealing helicase SMARCAL1 (SWI/SNF-related, matrix-associated, actindependent regulator of chromatin, subfamily a-like 1) cause Schimke immuno-osseous dysplasia (SIOD, MIM 242900), an incompletely penetrant autosomal recessive disorder. Using human, Drosophila and mouse models, we show that the proteins encoded by SMARCAL1 orthologs localize to transcriptionally active chromatin and modulate gene expression. We also show that, as found in SIOD patients, deficiency of the SMARCAL1 orthologs alone is insufficient to cause disease in fruit flies and mice, although such deficiency causes modest diffuse alterations in gene expression. Rather, disease manifests when SMARCAL1 deficiency interacts with genetic and environmental factors that further alter gene expression. We conclude that the SMARCAL1 annealing helicase buffers fluctuations in gene expression and that alterations in gene expression contribute to the penetrance of SIOD

Immune and hormonal activity in adults suffering from depression

An association between depression and altered immune and hormonal systems has been suggested by the results of many studies. In the present study we carried out immune and hormonal measurements in 40 non-medicated, ambulatory adult patients with depression determined by CID-10 criteria and compared with 34 healthy nondepressed subjects. The severity of the condition was determined with the Hamilton Depression Rating Scale. Of 40 depressed patients, 31 had very severe and 9 severe or moderate depression, 29 (72.5%) were females and 11 (27.5%) were males (2.6:1 ratio). The results revealed a significant reduction of albumin and elevation of alpha-1, alpha-2 and ß-globulins, and soluble IL-2 receptor in patients with depression compared to the values obtained for nondepressed subjects (P<0.05). The decrease lymphocyte proliferation in response to a mitogen was significantly lower in severely or moderately depressed patients when compared to control (P<0.05). These data confirm the immunological disturbance of acute phase proteins and cellular immune response in patients with depression. Other results may be explained by a variety of interacting factors such as number of patients, age, sex, and the nature, severity and/or duration of depression. Thus, the data obtained should be interpreted with caution and the precise clinical relevance of these findings requires further investigation