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- ItemAcesso aberto (Open Access)Anticorpo anticitoplasma de neutrófilos (ANCA) em pioderma gangrenoso, um marcador sorológico para associação com doenças sistêmicas: estudo de oito casos(Sociedade Brasileira de Dermatologia, 2004-02-01) Cabral, Virgínia Lúcia Ribeiro [UNIFESP]; Miszputen, Sender Jankiel [UNIFESP]; Catapani, Wilson Roberto; Universidade Federal de São Paulo (UNIFESP); Faculdade de Medicina do ABCBACKGROUND: The pathogenesis of Ulcerative Colitis (UC) and its extraintestinal manifestations remain uncertain, although involvement of the immune system is emphasized. The likely importance of neutrophils is demonstrated by detection of the antineutrophil cytoplasmic antibody (ANCA) in this inflammatory bowel disease. Pyoderma Gangrenosum (PG) is an idiopathic skin condition and a rare cutaneous manifestation of UC. ANCA has also been reported in the latter dermatosis. OBJECTIVES: To invetigate the relationship between clinical features of UC and the appearance of PG and its association with ANCA. PATIENTS AND METHODS: ANCA was determined in sera from eight patients with PG. Four out of eight patients had pyoderma gangrenosum associated-UC, and in four cases no identified systemic disease was associated. RESULTS: The search for ANCA yielded negative results in sera from all four patients with pyoderma not associated with systemic disease. Two cases with active and extensive colitis associated with PG and primary sclerosing cholangitis (PSC) were positive for ANCA. Sera from two other patients with both UC and PG had negative test results. CONCLUSIONS: The presence of ANCA in patients with PG associated with UC and PSC suggests that its association with PSC is responsible for ANCA positivity in this subset of patients.
- ItemAcesso aberto (Open Access)Caracterização clínica, molecular e imunológica de pacientes com síndrome poliglandular autoimune do tipo 1(Universidade Federal de São Paulo (UNIFESP), 2016-01-27) Weiler, Fernanda Guimarães [UNIFESP]; Castro, Marise Lazaretti [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Introduction: Autoimmune polyendocrine syndrome type 1 (APS1) is an autosomal recessive disorder defined by the association of at least two of the three major diseases: chronic mucocutaneous candidiasis (CMC), hypoparathyroidism, and autoimmune adrenal insufficiency, however, many other autoimmune components may develop. In most cases, APS1 appears in infancy or childhood. The disease is caused by mutations in the AIRE gene, resulting in defective AIRE protein, which is essential for self-tolerance through thymic expression of peripheral self-proteins, and deletion of autoreactive T cells. In Brazil, however, the characteristics of APS1 patients are still unknown. Objective: To define the clinical profile of Brazilian APS1 patients; to perform mutational analysis of AIRE gene; to investigate genotype/phenotype correlations; to perform functional study of a novel mutation; and to measure specific autoantibodies. Patients and methods: Information about clinical history was evaluated by a questionnaire, and antibodies against interferon type I and interleukins 17A, 17F and 22 were measured in the sera of the patients. Genomic DNA was used to perform sequencing of all 14 exons and exon/intron boundaries of the AIRE gene. For localization analysis by immunofluorescence microscopy, HeLa cells were transfected with wild-type and mutant (c.560C>G) plasmids. Results: Thirteen patients with clinical diagnosis of APS1 were identified and in all cases the disease first appeared during infancy or childhood. Twenty different manifestations have been diagnosed. Besides being the first sign in the majority (77%), CMC was also the most frequent manifestation, present in all patients. Hypoparathyroidism was observed in 69% and adrenal insufficiency was diagnosed in 77%, while the complete triad was present in 54% of the sample. Every patient carried defects in AIRE, and among 10 identified mutations, 4 have never been reported (c.560C>G, c.966C>A, c.1096-2A>G and c.1347C>A). The most frequent mutation was the c.967_979del, which accounted for 36% of the alleles. As in other series, we were unable to identify correlations between phenotype and the detected mutations. Mutational analyses of relatives allowed the identification of APS1 in an asymptomatic child. In transiently transfected cells, the mutant c.560C>G protein was observed as abnormal perinuclear aggregates, which suggested the mutation harmful potential. All 10 confirmed APS1 patients that were tested for anti-interferon type I showed positive results, and we have found that anti-interleukin-17A titers were negatively correlated with number of manifestations in each patient. Thirteen patients suspected of having the syndrome were also investigated; one of them displayed another new mutation of AIRE, which is expected to be deleterious according to in silico simulations. Conclusions: We were able to identify 14 Brazilian patients with APS1, one of them still asymptomatic. In our cohort, CMC was the most prevalent disease, while the most common mutation was c.967_979del. We detected 4 novel mutations, and another mutation likely to be deleterious in a patient suspected of having the syndrome was also reported. Titers of anti-interleukin-17A were negatively correlated with number of manifestations. Screening for AIRE mutations and analysis of specific auto-antibodies are useful tools to establish the diagnosis in initial or atypical situations.
- ItemSomente MetadadadosA Dynamical Modeling to Study the Adaptive Immune System and the Influence of Antibodies in the Immune Memory(Tech Science Press, 2009-05-01) Castro, Alexandre de [UNIFESP]; Fronza, Carlos Frederico [UNIFESP]; Alves, Domingos [UNIFESP]; Empresa Brasileira de Pesquisa Agropecuária (EMBRAPA); Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)Immunological systems have been an abundant inspiration to contemporary computer scientists. Problem solving strategies, stemming from known immune system phenomena, have been successfully applied to chall enging problems of modem computing. Simulation systems and mathematical modeling are also beginning use to answer more complex immunological questions as immune memory process and duration of vaccines, where the regulation mechanisms are not still known sufficiently (Lundegaard, Lund, Kesmir, Brunak, Nielsen, 2007). In this article we studied in machina a approach to simulate the process of antigenic mutation and its implications for the process of memory. Our results have suggested that the durability of the immune memory is affected by the process of antigenic mutation.and by populations of soluble antibodies in the blood. The results also strongly suggest that the decrease of the production of antibodies favors the global maintenance of immune memory.
- ItemSomente MetadadadosEarly Increase in Autoantibodies Against Human Oxidized Low-Density Lipoprotein in Hypertensive Patients After Blood Pressure Control(Nature Publishing Group, 2010-02-01) Brandao, Sergio A. [UNIFESP]; Izar, Maria C. [UNIFESP]; Fischer, Simone M. [UNIFESP]; Santos, Andreza O. [UNIFESP]; Monteiro, Carlos M. [UNIFESP]; Povoa, Rui M. [UNIFESP]; Helfenstein, Tatiana [UNIFESP]; Carvalho, Antonio C. [UNIFESP]; Monteiro, Andrea M.; Ramos, Eduardo; Gidlund, Magnus; Figueiredo Neto, Antonio M.; Fonseca, Francisco A. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)BACKGROUNDOxidized lipoproteins and antioxidized low-density lipoprotein (anti-oxLDL) antibodies (Abs) have been detected in plasma in response to blood pressure (BP) elevation, suggesting the participation of the adaptive immune system. Therefore, treatment of hypertension may act on the immune response by decreasing oxidation stimuli. However, this issue has not been addressed. Thus, we have here analyzed anti-oxLDL Abs in untreated (naive) hypertensive patients shortly after initiation of anti hypertensive therapeutic regimens.METHODSTiters of anti-oxLDL Abs were measured in subjects with recently diagnosed hypertension on stage 1 (n = 94), in primary prevention of coronary disease, with no other risk factors, and naive of anti hypertensive medication at entry. Subjects were randomly assigned to receive perindopril, hydrochlorothiazide (HCTZ), or indapamide (INDA) for 12 weeks, with additional perindopril if necessary to achieve BP control. Abs against copper-oxidized LDL were measured by enzyme-linked immunosorbent assay.RESULTSTwelve-week antihypertensive treatment reduced both office-based and 24-h ambulatory BP measurements (P < 0.0005). the decrease in BP was accompanied by reduction in thiobarbituric acid-reactive substances (TBARS) (P < 0.05), increase in anti-oxLDL Ab titers (P < 0.005), and improvement in flow-mediated dilation (FMD) (P < 0.0005), independently of treatment. Although BP was reduced, we observed favorable changes in anti-oxLDL titers and FMD.CONCLUSIONSWe observed that anti-oxLDL Ab titers increase after antihypertensive therapy in primary prevention when achieving BP targets. Our results are in agreement with the concept that propensity to oxidation is increased by essential hypertension and anti-oxLDL Abs may be protective and potential biomarkers for the follow-up of hypertension treatment.
- ItemSomente MetadadadosParacoccidioides brasiliensis-reactive antibodies in Brazilian blood donors(B I O S Scientific Publishers Ltd, 2002-08-01) Botteon, FAG; Camargo, Zoilo Pires [UNIFESP]; Benard, G.; Coelho, R. F.; Chamone, DAF; Itano, E. N.; Universidade Estadual de Londrina (UEL); Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP); Hemoctr Reg Londrina; Fdn Pro SanguelIn a survey for primary paracoccidioidomycosis (PCM) infection (and not the clinical disease), two groups of blood donors were analyzed. One study group was drawn from donors living in a rural area where PCM is endemic, and the other group from urban residents of a large city, São Paulo. Anti-Paracoccidioides brasiliensis (Pb) specific antibodies (IgG) in sera were analyzed by ELISA, using crude Pb exoantigens (exoAg) and purified specific Pb 43 kDa glycoprotein (gp43). the results showed that 21% of 700 rural samples and 0.9% of 350 urban samples were positive for exoAg and gp43. To avoid cross-reactions, the sera were adsorbed first with Histoplasma capsulatum antigens and secondly with Leishmania amazonensis antigens. in the first adsorption with H. capsulatum, reactivity to gp43 fell to 12.8% in the rural group and to 0% in the urban group. in the succeeding adsorption with L. amazonensis, this reactivity fell to 12.3% in the rural group. There was a statistically greater proportion of persons with gp43-reactive antibodies in rural group than in the urban group, indicating that rural residents had frequently become exposed to Pb and contracted primary, subclinical PCM. the present report is the first epidemiological study using ELISA to detect antibodies against gp43 in blood donors.
- ItemAcesso aberto (Open Access)Placental transfer of Haemophilus influenzae type b antibodies in malnourished pregnant women(Brazilian Society of Infectious Diseases, 2008-02-01) Cavalcante, Rejane Silva [UNIFESP]; Kopelman, Benjamin Israel [UNIFESP]; Costa-Carvalho, Beatriz Tavares [UNIFESP]; University State of Pará Department of Integrated Health; Universidade Federal de São Paulo (UNIFESP)This study evaluated the vaccination response to Haemophilus influenzae type b (Hib) in malnourished pregnant women (MN), cord blood (CB) and in infants at two and six months of age for comparison with a control group (C). Twenty-eight malnourished pregnant women and 29 pregnant controls were immunized with conjugated Act-HIB® in the third trimester of pregnancy. Blood samples were collected from all before the immunization, during labor (post immunization), and from CB. All infants were immunized with Hib vaccine according to normal vaccine schedule and sera were collected at two and six months of age. Antibody levels to polyribosylribitol phosphate (PRP) were similar for both groups. Preimmunization: MN 1.94 µg/mL, C 1.68 µg/mL; post-vaccination: MN 18.53 µg/mL and C 17.55 µg/mL; in CB from MN 14.46 µg/mL and from C 17.04 µg/mL. Infants from MN and C mothers presented respectively at two months: 5.18 µg/mL and 8.60 µg/mL and at six months: MN 3.42 µg/mL and C 2.18 µg/mL. Antibody levels were similar in both groups studied (p = 0.485), however the vertical transmission rate was 14% lower in the MN pregnant group. Levels of antibodies > 0.15 µg/mL were found in all newborns from the MN pregnant group. Pregnant MN presented an immunological response to Hib vaccine similar to group C, however, vertical transmission rate of antibodies to PRP in the MN pregnant group was 14% lower than that in C, suggesting a less efficient passage of antibodies within this group.
- ItemSomente MetadadadosPolysaccaride pneumococcal antibodies - Placental transfer in normal infants and in patients with Down's syndrome and ataxia telangiectasia(Hogrefe & Huber Publishers, 2007-09-01) Costa-Carvalho, Beatriz Tavares; Universidade Federal de São Paulo (UNIFESP)Background: Streptococcus pneumoniae is the most common cause of respiratory tract infections such as acute otitis media (AOM), sinusitis, and pneumonia in children. in addition, it is the leading cause of serious community-acquired infections including bacteremia and meningitis. the most effective strategy used to reduce the burden of disease caused by S. pneumoniae is vaccination. in the first months of life, maternal antibodies transferred by the placenta provide protection against some extracellular bacteria, but this protection can be reduced in infants born prematurely or of mothers with compromised immune defenses.Methods/Data base: A review of the literature, focusing on pneumococcal antibodies in cord blood and in two immunodeficiency groups: Ataxia telangiectasia (AT) and Down's syndrome (DS), also examining the effects of vaccination.Results/Conclusions: Infections by Streptococcus pneumoniae still remain a challenge to be solved, particularly in infants and in patients with immunologic disorders. Vaccination effects are reduced in Down syndrome and Ataxia-telangiectasia patients but perhaps the small quantity of antibodies produced can have some benefits for these patients.
- ItemAcesso aberto (Open Access)Production, characterization, and application of antibodies against heat-labile type-I toxin for detection of enterotoxigenic Escherichia coli(Instituto Oswaldo Cruz, Ministério da Saúde, 2006-12-01) Menezes, Caroline A; Imamura, Sergio Y; Trabulsi, Luiz Rachid; Fernandes-Filho, Antônio; Martinez, Marina B; Guth, Beatriz Ernestina Cabilio [UNIFESP]; Girão, Dennys M; Piazza, Roxane Mf; Instituto Butantan Laboratório de Bacteriologia; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP); Universidade Federal do Rio de Janeiro Instituto Prof. Paulo de Góes Departamento de Microbiologia MédicaStrains of enterotoxigenic Escherichia coli (ETEC) are responsible for significant rates of morbidity and mortality among children, particularly in developing countries. The majority of clinical and public health laboratories are capable of isolating and identifying Salmonella, Shigella, Campylobacter, and Escherichia coli O157:H7 from stool samples, but ETEC cannot be identified by routine methods. The method most often used to identify ETEC is polymerase chain reaction for heat-stable and heat-labile enterotoxin genes, and subsequent serotyping, but most clinical and public health laboratories do not have the capacity or resources to perform these tests. In this study, polyclonal rabbit and monoclonal mouse IgG2b antibodies against ETEC heat-labile toxin-I (LT) were characterized and the potential applicability of a capture assay was analyzed. IgG-enriched fractions from rabbit polyclonal and the IgG2b monoclonal antibodies recognized LT in a conformational shape and they were excellent tools for detection of LT-producing strains. These findings indicate that the capture immunoassay could be used as a diagnostic assay of ETEC LT-producing strains in routine diagnosis and in epidemiological studies of diarrhea in developing countries as enzyme linked immunosorbent assay techniques remain as effective and economical choice for the detection of specific pathogen antigens in cultures.