As Imunodeficiências primárias (IDPs) incluem um grupo heterogêneo de doenças, que resultam de distúrbios do sistema imunológico, aumentando a susceptibilidade a infecções. Os avanços terapêuticos têm propiciado maior sobrevida destes pacientes, assim como necessidades nutricionais. O objetivo deste estudo foi comparar o estado nutricional nos diferentes grupos de IDP, avaliados através dos seguintes escores Z: peso, estatura e IMC para idade e da distribuição dos percentis de circunferência muscular do braço (CMB) e dobra cutânea triciptal (DCT) para idade. Também foram realizados exames laboratoriais relacionados à avaliação nutricional. Foram avaliados 72 pacientes da Unidade de Alergia e Imunologia do ICr- HCFMUSP com diagnóstico definitivo ou provável de IDP, com idade entre 3 e 19 anos, alocados em três grupos de IDP: humoral (n=44), fagócitos (n=12) e celular ou combinada (n=19). Os três grupos foram descritos através de suas idades, sexo, peso e estatura, e com base nestes dados, determinou-se o escore Z de estatura para idade e o escore Z de IMC para idade. Para cada um desses escores Z, foram calculados: a média, o desviopadrão e o intervalo de confiança 95%, sendo as médias obtidas comparadas por ANOVA e posteriormente o teste POST HOC de Tukey- Kramer. Para avaliação de ingestão alimentar foram realizados: o recordatório alimentar de 24 horas e o questionário de frequência alimentar. Observou-se que os grupos de IDP celular ou combinada e de fagócitos apresentaram médias de escore Z de estatura e IMC menores do que o grupo IDP predominantemente humoral. As médias de escore Z de peso para idade não apresentaram diferença estatisticamente significante, entretanto o grupo predominantemente humoral teve a maior média. No grupo de IDP predominantemente humoral não houve diferenças estatisticamente significantes entre os subgrupos. A CMB estava abaixo do percentil 15 em 25% dos pacientes do grupo IDP predominantemente humoral; 55,5% do grupo de IDP de fagócitos; 68,4% do grupo de IDP celular ou combinada. Em relação à DCT, estavam abaixo do percentil 15: 18,1% dos pacientes do grupo IDP predominantemente humoral; 11% do grupo de IDP de fagócitos; e 36,8% do grupo de IDP celular ou combinada. A ingestão protéica excedeu o recomendado em 77%, 100% e 84,2% dos pacientes nos grupos de IDP predominantemente humoral, IDP de fagócitos e IDP celular ou combinada, respectivamente. Os grupos de IDP predominantemente humoral, IDP de fagócitos e IDP celular ou combinada apresentaram elevadas concentrações de colesterol. Em conclusão, observou-se déficit do estado nutricional mais intenso nos pacientes com IDP celular ou combinada e de fagócitos. O aumento de colesterol e a redução da CMB podem sugerir um distúrbio metabólico relacionado à inflamação crônica dos pacientes imunodeficientes, com risco para doença cardiovascular no futuro. / Primary immunodeficiencies (PID) include a heterogeneous group of diseases with immunological system disturbance, increasing susceptibility to infections. The therapeutic advances have increased life span of these patients, as well as the nutritional needs. The aim of this study was to compare the nutritional status of patients from different immunodeficiency groups evaluated by the following Z scores means: weight for age, height for age, body mass index (BMI) for age and the percentiles distribution of upper arm muscle circumference (UAMC) and triceps skin fold thickness (TSF) for age. Laboratorial exams related to nutritional status were also carried out. Among patients from Allergy and Immunology Unit from ICr-HCFMUSP, 72 patients with definitive or probable diagnosis were evaluated, with age from 3 to 19 years allocated in 3 PID groups: humoral (n=44), phagocytes (n=12) and cellular or combined (n=19). These three groups were described through age, gender, weight and height. Through these data, were determined the weight for age, height for age, and BMI for age Z scores. There were calculated for each Z score: the mean, standard-deviation and confidence interval 95%, being the obtained means compared by ANOVA and after, the Tukey-Kramer post hoc test. There were evaluated for intake food: a 24-hour recall and a food frequency questionnaire. It was observed that the cellular or combined and phagocyte groups presented lower height for age and BMI for age Z score means than the humoral group. The weight for age Z score means didnt show significant statistical difference, however the humoral group had the highest mean. Among the subgroups from humoral group was not found significant statistical difference. The UAMC was below the 15th percentile mean in 25% of the humoral group, 55.5% from the phagocyte group and 68.4% from the cellular or combined group. About TSF, 18.1% of patients from humoral group, 11% from phagocyte group and 36.8% from the cellular or combined group were below 15th percentile. The protein intake exceeded the RDA in 77%, 100% and 84.2% in patients from humoral, phagocyte and cellular or combined groups, respectively. The humoral, phagocyte and cellular or combined groups presented high cholesterol levels. In conclusion, it was observed more severe nutritional impairment in cellular or combined and phagocyte PID than the humoral group. The high cholesterol level and the UAMC reduction may suggest a metabolic disturbance related to chronic inflammation in PID patients, with risk for cardiovascular chronic disease in the future.

Introdução: A globulina anti-timocitária (ATG) é um anticorpo policlonal depletor de linfócitos amplamente utilizado no transplante de órgãos. O monitoramento deste agente em receptores de transplante renal pode ser realizado por contagem de linfócitos totais e células T CD3+ no sangue periférico. Objetivo: Avaliar a correlação entre estas duas formas de monitorização. Métodos: Estudo retrospectivo, centro único, avaliou 226 pacientes que receberam enxerto renal entre 2008 e 2013 e que foram tratados com ATG para terapia de indução ou para tratamento de rejeição celular aguda grave. A primeira dose foi administrada no intra-operatório e as subsequentes de acordo com os níveis de células T CD3+ ou número de linfócitos totais no sangue periférico. Os coeficientes de correlação e concordância foram avaliados em amostras pareadas. Resultados: No total 664 amostras pareadas foram analisadas para o número de linfócitos totais e células T CD3+. O coeficiente de correlação de Spearman enre os resultados foi 0.416 (P <0.001) para a amostra geral, 0.435 (P < 0.001) para os pacientes em indução e 0.285 (P<0.005) para os pacientes em tratamento de rejeição. O coeficiente de concordância Kappa entre as amostras gerais foi 0.267 (P < 0.001), 0.280 (P < 0.001) para indução e 0.155 (P<0.081) para pacientes em tratamento. Os parâmetros diagnósticos para a contagem de linfócitos totais foram calculados usando o número de células T CD3+ como padrão-ouro com o ponto de corte de > 20 células/mm³. Na curva ROC o melhor ponto (256 linfócitos/mm3) apresenta área sobre a curva de 0.71 (95% CI: 0.67-0.75) com sensibilidade de 66.8%, especificidade 66.5%, valor preditivo positivo 46.6% e valor preditivo negativo 82.1%. Conclusão: Baseados nestes resultados consideramos que a monitorização da administração e do intervalo das doses de ATG deva ser realizada através da contagem de células T CD3+, por citometria de fluxo, em detrimento dos linfócitos totais no sangue periférico. / Background: Anti-thymocyte globulin (ATG) is a preparation of depleting antibodies largely utilized in organ transplantation. The monitoring of this agent in renal transplant recipients can be accomplished by counting total lymphocytes and CD3+T cells in the peripheral blood. Objective: Evaluated the correlation between these two measurements. Methods: Retrospective study, single center study that evaluated 226 patients who received a kidney graft between 2008 and 2013 and where treated with ATG either for induction therapy or for treatment a severe acute cellular rejection. The first dose was given intra-operatively and subsequent doses were administered according to the levels of CD3+ T cells or number of total lymphocytes in the peripheral blood. Correlation and concordance coefficients were evaluated in paired samples. Results: A total of 664 paired samples were analyzed for the number of lymphocytes and CD3+ T. The Spearman’s correlation coefficient between the results was 0.416 (P < 0.001) to all samples, 0.435 (P < 0.001) for induction therapy samples and 0.285 (P<0.005) for therapeutic samples. The Kappa’s concordance coefficient between samples was 0.267 (P < 0.001) to all samples, 0.280 (P < 0.001) for induction therapy samples and 0.155 (P<0.081) for therapeutic samples. The diagnostic parameters for the total lymphocyte counting were calculated using number of CD3+ T cells as the gold standard at the cut off at > 20 cells/mm³. At the ROC curve using the best cut off (256 lymphocytes/mm3) an AUC of 0.71 (95% CI: 0.67-0.75) was found along with a sensitivity 68.8%, specificity 66.5%, positive predictive value 46.6% and negative predictive value 82.1%. Conclusion: Based upon these results it is not possible to reliably replace the flow cytometric assay for CD3+ T cells by the counting of total lymphocytes in the peripheral blood in the monitoring of ATG administration in kidney transplant recipients.

Immunologic competence is correlated with resistance to infectious disease which may be affected by exposure to certain compounds. Methyl parathion (MP) and carbofuran (CF) have been reported to affect the development of active immunity in the rabbit and the present research was conducted to quantify the dosage relationships of these two pesticides to both host resistance and acquired resistance in the mouse. Preliminary study was made on the virulence of Salmonella typhimurium in mice. Mortality rates among infected animals fed Purina Laboratory Chow diet providing 0.08, 0.7 3.0 mg MP/kg/day or 0.1, 0.6, 1.0 mg CF/kg/day along with untreated controls were determined and protection afforded the animals by vaccination under the influence of chemical treatment was examined. The nature of dose response was further investigated with the study of various parameters of host defense against microbial infection. Measurements were made of the bacterial population in tissues of mice during and after the course of infection, differential leukocyte counts, in vivo and in vitro opsonic effect of serum, clearance of the reticulo-endothelial system, agglutination titers of serum, total serum gamma-globulin levels, serum immunoglobulin levels with classes and subclasses, and lymphocyte response to mitogen stimulation. Dosage-related increases in mortality were seen in unvaccinated mice under both chemical treatments, and protection by immunization was decreased. Pesticide treatment extending beyond two weeks was required to obtain significant increases in mortality. Increased mortality was associated with increased numbers of viable bacteria in blood, decreased total gamma-globulins and specific immunoglobulins in serum, and reduced splenic blast transformation in response to mitogens. Serum opsonic activity of CF-treated animals was slightly reduced. These results support those of other investigations indicating effects of environmental toxicants upon the resistance and immune competency of experimental animals.

Thesis (Ph. D.)--Cornell University, January, 2007. / Vita. Includes bibliographical references (leaves 92-106).

Access to abstract restricted until May 2016. / Access to thesis restricted until May 2016 / Department of Biology

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 5 uppsatser.

Diss. (sammanfattning) Uppsala : Univ., 2002. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2002. / Härtill 4 uppsatser.