Tais Nitsch Mazzola

Impaired Humoral Response to Vaccines among HIV-Exposed Uninfected Infants

ABSTRACT Little is known about the vaccine protective response for infants born from HIV-infected mothers. We evaluated the antibody response to hepatitis B, tetanus, and diphtheria vaccine in vertically HIV-exposed uninfected infants and compared them to those of control infants not exposed to the virus. The quantitative determination of specific neutralizing antibodies against hepatitis B, diphtheria, and tetanus were performed blindly on serum samples. The results showed that 6.7% of the HIV-exposed uninfected individuals were nonresponders to hepatitis B vaccine (anti-HBs titer, <10 mIU/ml), and 64.4% were very good responders (anti-HBs titer, ≥1,000 mIU/ml), whereas only 3.6% of the nonexposed infants were nonresponders (χ2=10.93; 1 df). The HIV-exposed uninfected infants showed protective titers for diphtheria and tetanus but lower geometric mean anti-tetanus titers compared to those of the HIV-unexposed infants. Our data point to the necessity of evaluating vaccine immune responses in these children and reinforced that alterations in lymphocyte numbers and functions reported for newborns from HIV-infected mothers interfere with the vaccine response.

Impaired Bacillus Calmette-Guérin cellular immune response in HIV-exposed, uninfected infants.

Objective:To evaluate cell-mediated immune response to Bacillus Calmette–Guérin (BCG) vaccination in uninfected, HIV-1-exposed infants, comparing it with unexposed children. Design:It is designed as a cross-sectional study. Methods:BCG-specific lymphoproliferation and T-cell subsets (CD4+, CD8+ and TCR &ggr;&dgr;+) by flow cytometry and interleukin-10, interferon-&ggr; (IFN-&ggr;) and tumor necrosis factor-&agr; (TNF-&agr;) concentration by ELISA were analyzed in HIV-exposed and unexposed infants. Whole blood lymphocyte immunophenotyping and blood counts were performed in exposed children. Nonparametric tests were used (P < 0.05). Results:Given the ontogeny of the immune system, exposed infants were separated into three groups according to age: exposed 1 (E1, aged 6.1–8.8 months), E2 (aged 9.1–17.1 months) and E3 (aged 18.1–26.3 months). Unexposed infants (UE group) and E1 were matched for age. Cell proliferation was not different among the three exposed groups, neither for BCG nor for phytohemagglutinin (PHA)-stimulated cultures. Furthermore, BCG-stimulated lymphoproliferation was reduced in the E1 group in comparison with the UE group. T-lymphocyte subpopulations also showed differences, with the youngest HIV-exposed groups (E1 and E2) showing a predominant proliferation of CD4+ T cells in cultures with BCG, whereas E3 and UE groups had a robust &ggr;&dgr;+ T-cell expansion. There was lower IFN-&ggr; concentration in the samples from E1 group in comparison with all of the other groups. The unexposed infants showed higher TNF-&agr; concentration in cultures with BCG and PHA in comparison with E1 group. Conclusion:BCG-specific T-cell proliferation was reduced in HIV-exposed uninfected infants and IFN-&ggr; concentration was lower in younger exposed infants, showing a delay in immune system maturation of HIV-exposed infants.

Immunogenicity of a Whole-Cell Pertussis Vaccine with Low Lipopolysaccharide Content in Infants

ABSTRACT The lack of a clear correlation between the levels of antibody to pertussis antigens and protection against disease lends credence to the possibility that cell-mediated immunity provides primary protection against disease. This phase I comparative trial had the aim of comparing the in vitro cellular immune response and anti-pertussis toxin (anti-PT) immunoglobulin G (IgG) titers induced by a cellular pertussis vaccine with low lipopolysaccharide (LPS) content (wPlow vaccine) with those induced by the conventional whole-cell pertussis (wP) vaccine. A total of 234 infants were vaccinated at 2, 4, and 6 months with the conventional wP vaccine or the wPlow vaccine. Proliferation of CD3+ T cells was evaluated by flow cytometry after 6 days of peripheral blood mononuclear cell culture with stimulation with heat-killed Bordetella pertussis or phytohemagglutinin (PHA). CD3+, CD4+, CD8+, and T-cell receptor γδ-positive (γδ+) cells were identified in the gate of blast lymphocytes. Gamma interferon, tumor necrosis factor alpha, interleukin-4 (IL-4), and IL-10 levels in supernatants and serum anti-PT IgG levels were determined using enzyme-linked immunosorbent assay (ELISA). The net percentage of CD3+ blasts in cultures with B. pertussis in the group vaccinated with wP was higher than that in the group vaccinated with the wPlow vaccine (medians of 6.2% for the wP vaccine and 3.9% for the wPlow vaccine; P = 0.029). The frequencies of proliferating CD4+, CD8+, and γδ+ cells, cytokine concentrations in supernatants, and the geometric mean titers of anti-PT IgG were similar for the two vaccination groups. There was a significant difference between the T-cell subpopulations for B. pertussis and PHA cultures, with a higher percentage of γδ+ cells in the B. pertussis cultures (P < 0.001). The overall data did suggest that wP vaccination resulted in modestly better specific CD3+ cell proliferation, and γδ+ cell expansions were similar with the two vaccines.

Antenatal maternal corticosteroid administration and markers of oxidative stress and inflammation in umbilical cord blood from very low birth weight preterm newborn infants

OBJECTIVE To investigate the association between antenatal maternal corticosteroid administration and blood levels of reactive oxygen intermediates (ROI), reduced glutathione (GR) and interleukin-6 (IL-6) in preterm, very low birth weight infants. METHODS This was a cohort study in which cord blood samples were used for the following tests: baseline and stimulated granulocyte ROI were measured by flow cytometry; GR was assayed by spectrophotometry; and IL-6 by enzyme-linked immunosorbent assay. Two different comparative analyses of antenatal corticosteroid (betamethasone) were conducted: the first compared administration against no administration and the second compared mothers who received the complete cycle with those given only a partial antenatal corticosteroid cycle. Maternal and neonatal variables were analyzed in order to compare groups. Categorical variables were compared using the chi-square or Fischer tests, and blood marker test results were compared using the Mann-Whitney test. RESULTS The different corticoid therapy groups were similar in terms of all of the maternal and neonatal variables with the exception of vaginal delivery, which was significantly associated with not receiving antenatal corticosteroid. The results for ROI, GR and IL-6 did not differ when the comparison was based on simple presence or absence of administration of the steroid. However, when the complete cycle was compared against incomplete administration, median ROI and IL-6 were lower among those given the complete cycle. CONCLUSION Administration of the complete cycle of betamethasone to the mother had a suppressive effect on baseline ROI and IL-6 production in very low birth weight preterm newborn infants.

The impact of cystic fibrosis on the immunologic profile of pediatric patients

OBJECTIVE To compare the immunologic state of 44 pediatric patients with cystic fibrosis (CF) with a control group consisting of 16 healthy individuals. METHODS CF patients aged 3 to 12 years with moderate to good clinical score were selected for the study. Erythrocytic glutathione, production of reactive oxygen species, cytokines (TNF-a, IFN-g, IL-8, IL-6, IL-10) in peripheral blood mononuclear cells cultures under spontaneous and BCG- or PHA-stimulated conditions, serum concentrations of TGF-b2, IgA, IgG, IgM, IgE, and salivary IgA were evaluated. RESULTS The spontaneous production of TNF-a, IL-6, and IL-10, the PHA-stimulated production of IL-6, and the serum TGF-b2, IgA, and IgG were increased in samples from CF patients. Healthy subjects had a higher production of TNF-a in response to BCG. CONCLUSION Although CF patients appeared clinically stable, the results of their peripheral blood examinations demonstrated an impact on the immune system.

Peri-intraventricular hemorrhage and oxidative and inflammatory stress markers in very-low birth weight newborns

OBJECTIVES To evaluate the association between oxidative and inflammatory stress markers with peri-intraventricular hemorrhage (PIVH) in very-low birth weight newborns. METHODS This was a prospective study conducted in a level III neonatal unit. Basal and stimulated reactive oxygen intermediates (ROIs), reduced glutathione (GSH), and interleukin-6 (IL-6) levels were measured in umbilical cord blood. Newborns underwent serial ultrasound at the bedside, at 6, 12, 24, and 72hours of life and at seven days for the diagnosis of PIVH, classified as grades I to IV. Two groups were assessed, those with and without PIVH; maternal and neonatal control variables were used for comparison. Univariate and multiple regression analyses were applied. RESULTS A total of 125 newborns were assessed. PIVH incidence rate was 12.0%. In the univariate analysis, basal ROI, the use of two or more doses of corticosteroids, birth weight<1,000g, ventilatory support use, and SNAPPE II value ≥ 22 were significantly associated with PIVH. However, in the multivariate analysis, only antenatal steroid use was independently associated with the disease (OR 0,194; 95% CI: 0,048 to 0,773; p=0,02). CONCLUSION ROI, GSH, and IL-6 levels were not associated with the occurrence of PIVH in very-low birth weight infants.

408 Cases of Genital Ambiguity Followed by Single Multidisciplinary Team during 23 Years: Etiologic Diagnosis and Sex of Rearing

Objective. To evaluate diagnosis, age of referral, karyotype, and sex of rearing of cases with disorders of sex development (DSD) with ambiguous genitalia. Methods. Retrospective study during 23 years at outpatient clinic of a referral center. Results. There were 408 cases; 250 (61.3%) were 46,XY and 124 (30.4%) 46,XX and 34 (8.3%) had sex chromosomes abnormalities. 189 (46.3%) had 46,XY testicular DSD, 105 (25.7%) 46,XX ovarian DSD, 95 (23.3%) disorders of gonadal development (DGD), and 19 (4.7%) complex malformations. The main etiology of 46,XX ovarian DSD was salt-wasting 21-hydroxylase deficiency. In 46,XX and 46,XY groups, other malformations were observed. In the DGD group, 46,XY partial gonadal dysgenesis, mixed gonadal dysgenesis, and ovotesticular DSD were more frequent. Low birth weight was observed in 42 cases of idiopathic 46,XY testicular DSD. The average age at diagnosis was 31.7 months. The final sex of rearing was male in 238 cases and female in 170. Only 6.6% (27 cases) needed sex reassignment. Conclusions. In this large DSD sample with ambiguous genitalia, the 46,XY karyotype was the most frequent; in turn, congenital adrenal hyperplasia was the most frequent etiology. Malformations associated with DSD were common in all groups and low birth weight was associated with idiopathic 46,XY testicular DSD.

Quality of sleep and quality of life in adolescents infected with human immunodeficiency virus

OBJECTIVES To assess sleep characteristics of adolescents infected by HIV, and to ascertain whether psychosocial aspects are associated to the quality of sleep. METHODS A cross-sectional study assessing 102 HIV-infected adolescents of both genders, aged between 10 and 20 years-old and 120 Controls. Data collection was performed by applying the Sleep Disturbance Scale for Children, the Epworth Sleepiness Scale, and the Pediatric Quality of Life Inventory. RESULTS A sleep disturbance prevalence of 77.4% was found in patients, and a 75% prevalence in controls, and there was correlation between quality of sleep and of life. HIV-infected adolescents scored higher for sleep breathing disorders and had higher prevalence of excessive daytime sleepiness. CONCLUSIONS HIV-infected adolescents had similar quality of sleep compared to healthy adolescents. This may be explained by the steady improvements in daily living as a result of successful anti-retroviral therapy, and by the vulnerability that affects Brazilian adolescents living in major urban centers.

Three new Brazilian cases of 17α-hydroxylase deficiency: clinical, molecular, hormonal, and treatment features.

Abstract Background: Deficiency of 17α-hydroxylase (17OHD) is a rare form of adrenal hyperplasia. Diagnosis is generally delayed, impairing appropriate treatment. Case presentation: Here, we report the clinical, molecular, hormonal, and treatment data of three unrelated 17OHD patients, aged 14–16 years with hypergonadotrophic hypogonadism; uncontrolled hypertension; primary adrenal insufficiency; and high progesterone, low to normal potassium, and low dehydroepiandrosterone, androstenedione, and testosterone levels. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) at baseline and after an adrenocorticotropic hormone test showed low cortisol and cortisone and high deoxycorticosterone (DOC) and corticosterone levels; both DOC/21-deoxycortisol and costicosterone/cortisol ratios were very high. Patient 2 had 46,XX karyotype and patients 1 and 3, had 46,XY. A molecular analysis showed that two of the patients were homozygous for p.W406R mutation and the other patient was compound heterozygous for p.W406R and p.P428L. Hypertension was controlled only after the administration of both prednisone and mineralocorticoid antagonist. Conclusions: Hypertension in young women must lead to diagnostic suspicion, even in the pre-pubertal period. The basal level of progesterone is an indicator of 17OHD. Mineral and glucocorticoid ratios obtained from LC-MS/MS can reinforce the diagnosis. Hypertension can be controlled using glucocorticoid replacement therapy and mineralocorticoid antagonist.

Original articleThe impact of cystic fibrosis on the immunologic profile of pediatric patientsO impacto da fibrose cística no perfil imunológico de pacientes pediátricos

Objective To compare the immunologic state of 44 pediatric patients with cystic fibrosis (CF) with a control group consisting of 16 healthy individuals.a Mestre, Nutrição e Alimentos. Departamento de Alimentos e Nutrição, Faculdade de Engenharia de Alimentos, Universidade Estadual de Campinas (UNICAMP), Campinas, São Paulo, Brasil b Doutor, Saúde da Criança e do Adolescente, Centro de Investigação em Pediatria, Departamento de Pediatria, Faculdade de Ciências Médicas, UNICAMP, Campinas, SP, Brasil c Mestre, Saúde da Criança e do Adolescente, Centro de Investigação em Pediatria, Departamento de Pediatria, Faculdade de Ciências Médicas, UNICAMP, Campinas, SP, Brasil d Doutor, Biologia (Imunologia), Centro de Investigação em Pediatria, Departamento de Pediatria, Faculdade de Ciências Médicas, UNICAMP, Campinas, SP, Brasil e Doutor, Nutrição. Departamento de Alimentos e Nutrição, Faculdade de Engenharia de Alimentos, UNICAMP, Campinas, São Paulo, Brasil