A Decreased Frequency of Regulatory T Cells in Patients with Common Variable Immunodeficiency

Introduction: Common variable immunodeficiency disorder (CVID) is a heterogeneous syndrome, characterized by deficient antibody production and recurrent bacterial infections in addition abnormalities in T cells. CD4(+)CD25(high) regulatory T cells (Treg) are essential modulators of immune responses, including down-modulation of immune response to pathogens, allergens, cancer cells and self-antigens.Objective: in this study we set out to investigate the frequency of Treg cells in CVID patients and correlate with their immune activation status.Materials and Methods: Sixteen patients (6 males and 10 females) with CVID who had been treated with regular intravenous immunoglobulin and 14 controls were enrolled. Quantitative analyses of peripheral blood mononuclear cells (PBMC) were performed by multiparametric flow cytometry using the following cell markers: CD38, HLA-DR, CCR5 ( immune activation); CD4, CD25, FOXP3, CD127, and OX40 (Treg cells); Ki-67 and IFN-gamma (intracellular cytokine).Results: A significantly lower proportion of CD4(+)CD25(high) FOXP3 T cells was observed in CVID patients compared with healthy controls (P<0.05). in addition to a higher proportion of CD8(+) T cells from CVID patients expressing the activation markers, CD38(+) and HLA-DR(+) (P<0.05), we observed no significant correlation between Tregs and immune activation.Conclusion: Our results demonstrate that a reduction in Treg cells could have impaired immune function in CVID patients.Universidade Federal de São Paulo, São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

Is age a risk factor for liver disease and metabolic alterations in ataxia Telangiectasia patients?

Background: Ataxia telangiectasia (A-T) is a neurodegenerative disease that leads to mitochondrial dysfunction and oxidative stress. Insulin resistance (IR), type 2 diabetes and the risk for development of cardiovascular disease was recently associated as an extended phenotype of the disease. We aimed to assess IRliver involvementcarotid intima-media thickness (cIMT) and metabolic alterations associated to cardiovascular risk in A-T patients, and relate them with age. Results: Glucose metabolism alterations were found in 54.6% of the patients. Hepatic steatosis was diagnosed in 11/17 (64.7%) A-T patients. AST/ALT ratio > 1 was observed in 10/17 (58.8%). A strong positive correlation was observed between insulin sum concentrations with ALT (r = 0.782, p < 0.004) and age (r = 0.818, p = 0.002). Dyslipidemia was observed in 55.5% of the patients. The apolipoprotein (Apo-B)/ApoA-I ratio (r = 0.619p < 0.01), LDL/HDL-c (r = 0.490p < 0.05) and the Apo-B levels (r = 0.545p < 0.05) were positively correlated to cIMT. Conclusions: Metabolic disorders implicated in cardiovascular and liver diseases are frequently observed in adolescent A-T patients and those tend to get worse as they become older. Therefore, nutritional intervention and the use of drugs may be necessary.CAPES Foundation, Ministry of Education of Brazil, Brasilia DF, BrazilFed Univ São Paulo UNIFESP, Escola Paulista Med, Dept Pediat, Rua Otonis 725, BR-04025002 São Paulo, SP, BrazilABC Fdn FMABC, Fac Med ABC, Dept Morphol & Physiol, Santo Andre, SP, BrazilFed Univ São Paulo UNIFESP, Escola Paulista Med, Dept Diagnost Imaging, São Paulo, SP, BrazilSanta Casa São Paulo Sch Med Sci FCMSCSP, São Paulo, SP, BrazilFed Univ Alfenas UNIFAL, Sch Nutr, Alfenas, MG, BrazilFed Univ São Paulo UNIFESP, Escola Paulista Med, Dept Pediat, Rua Otonis 725, BR-04025002 São Paulo, SP, BrazilFed Univ São Paulo UNIFESP, Escola Paulista Med, Dept Diagnost Imaging, São Paulo, SP, BrazilWeb of Scienc

[autosomal Chronic Granulomatous Disease: Case Report And Mutation Analysis Of Two Brazilian Siblings].

To report the case of two siblings with chronic granulomatous disease. Chronic granulomatous disease is a primary immunodeficiency disorder characterized by abnormal microbicidal activity. Mutations in the p47-phox gene (NCF-1) are present in about 30% of the patients with chronic granulomatous disease; this group presents a better prognosis and later onset of recurrent infections as compared with the X-linked variant, present in about 56% of patients. Case 1 is a female presenting repeat infections since age 10, starting with impetigo followed by severe pneumonia six months later. The severity of the lung infection associated with liver abscess and the patient's resistance to treatment prompted laboratory investigation for immunodeficiency. The results of the nitroblue tetrazolium and superoxide release tests were consistent with a diagnosis of chronic granulomatous disease. The parents and siblings were assessed, revealing the presence of granulomatous disease in a brother (Case 2). He also presented repeat infections with impetigo at age 10, followed by pneumonia six months later, however in a non severe form. Single-strand conformational polymorphism analysis detected abnormal electrophoretic mobility of exon 2 of the NCF-1 gene. Sequence DNA analysis revealed a dinucleotide GT deletion in exon 2. It is important to evaluate the relatives of chronic granulomatous disease patients, even in the absence of typical clinical signs. Defining the mutation and its correlation with phenotype is important to provide appropriate genetic counseling and clinical prognosis.80425-

Emerging Infections and Pertinent Infections Related to Travel for Patients with Primary Immunodeficiencies

Erratum: J Clin Immunol. 2017 Oct;37(7):693-694. doi: 10.1007/s10875-017-0436-0.In today's global economy and affordable vacation travel, it is increasingly important that visitors to another country and their physician be familiar with emerging infections, infections unique to a specific geographic region, and risks related to the process of travel. This is never more important than for patients with primary immunodeficiency disorders (PIDD). A recent review addressing common causes of fever in travelers provides important information for the general population Thwaites and Day (N Engl J Med 376:548-560, 2017). This review covers critical infectious and management concerns specifically related to travel for patients with PIDD. This review will discuss the context of the changing landscape of infections, highlight specific infections of concern, and profile distinct infection phenotypes in patients who are immune compromised. The organization of this review will address the environment driving emerging infections and several concerns unique to patients with PIDD. The first section addresses general considerations, the second section profiles specific infections organized according to mechanism of transmission, and the third section focuses on unique phenotypes and unique susceptibilities in patients with PIDDs. This review does not address most parasitic diseases. Reference tables provide easily accessible information on a broader range of infections than is described in the text.Peer reviewe

Glucose-6-phosphate dehydrogenase deficiency with recurrent infections: case report

OBJECTIVE: To report a case of rare neutrophil functional disorder with clinical and laboratory findings similar to those of chronic granulomatous disease. METHODS: Patient with extremely reduced level of glucose-6-phosphate dehydrogenase and recurrent infections that improved after continuous use of cotrimoxazole. The patient presented leukocytes with defective respiratory burst, similar to what occurs in chronic granulomatous disease. COMMENTS: The diagnosis of glucose-6-phosphate dehydrogenase deficiency in neutrophils should be considered in any patient with hemolytic anemia whose level of G6PD is extremely low or in any patient that presents recurrent infections as differential diagnosis of chronic granulomatous disease.OBJETIVO: relatar a ocorrência de uma deficiência funcional de neutrófilos rara, com quadro clínico e laboratorial semelhante ao da doença granulomatosa crônica. MÉTODOS: relato de caso de paciente com deficiência acentuada da glicose-6-fosfato desidrogenase e infecções de repetição. Realizada pesquisa bibliográfica utilizando as bases de dados Medline e Lilacs, abrangendo o período de 1972 a 2000. RESULTADOS: paciente com nível da glicose-6-fosfato desidrogenase extremamente reduzido e quadro de infeções graves com melhora clínica após uso de cotrimoxazol contínuo. Os leucócitos do paciente apresentam defeito no metabolismo oxidativo, similar ao da doença granulomatosa crônica. CONCLUSÕES: o diagnóstico da deficiência da glicose-6-fosfato desidrogenase em neutrófilos deve ser considerado em qualquer paciente com anemia hemolítica não esferocítica congênita no qual o nível da glicose-6-fosfato desidrogenase esteja anormalmente baixo ou apresente infeções de repetição. É diagnóstico diferencial da doença granulomatosa crônica.33133

Skewed Distribution of Circulating Activated Natural Killer T (NKT) Cells in Patients with Common Variable Immunodeficiency Disorders (CVID)

Common variable immunodeficiency disorder (CVID) is the commonest cause of primary antibody failure in adults and children, and characterized clinically by recurrent bacterial infections and autoimmune manifestations. Several innate immune defects have been described in CVID, but no study has yet investigated the frequency, phenotype or function of the key regulatory cell population, natural killer T (NKT) cells. We measured the frequencies and subsets of NKT cells in patients with CVID and compared these to healthy controls. Our results show a skewing of NKT cell subsets, with CD4+ NKT cells at higher frequencies, and CD8+ NKT cells at lower frequencies. However, these cells were highly activated and expression CD161. The NKT cells had a higher expression of CCR5 and concomitantly expression of CCR5+CD69+CXCR6 suggesting a compensation of the remaining population of NKT cells for rapid effector action

Beyond trees: Mapping total aboveground biomass density in the Brazilian savanna using high-density UAV-lidar data

Tropical savanna ecosystems play a major role in the seasonality of the global carbon cycle. However, their ability to store and sequester carbon is uncertain due to combined and intermingling effects of anthropogenic activities and climate change, which impact wildfire regimes and vegetation dynamics. Accurate measurements of tropical savanna vegetation aboveground biomass (AGB) over broad spatial scales are crucial to achieve effective carbon emission mitigation strategies. UAV-lidar is a new remote sensing technology that can enable rapid 3-D mapping of structure and related AGB in tropical savanna ecosystems. This study aimed to assess the capability of high-density UAV-lidar to estimate and map total (tree, shrubs, and surface layers) aboveground biomass density (AGBt) in the Brazilian Savanna (Cerrado). Five ordinary least square regression models esti-mating AGBt were adjusted using 50 field sample plots (30 m × 30 m). The best model was selected under Akaike Information Criterion, adjusted coefficient of determination (adj.R2), absolute and relative root mean square error (RMSE), and used to map AGBt from UAV-lidar data collected over 1,854 ha spanning the three major vegetation formations (forest, savanna, and grassland) in Cerrado. The model using vegetation height and cover was the most effective, with an overall model adj-R2 of 0.79 and a leave-one-out cross-validated RMSE of 19.11 Mg/ha (33.40%). The uncertainty and errors of our estimations were assessed for each vegetation formation separately, resulting in RMSEs of 27.08 Mg/ha (25.99%) for forests, 17.76 Mg/ha (43.96%) for savannas, and 7.72 Mg/ha (44.92%) for grasslands. These results prove the feasibility and potential of the UAV-lidar technology in Cerrado but also emphasize the need for further developing the estimation of biomass in grasslands, of high importance in the characterization of the global carbon balance and for supporting integrated fire management activities in tropical savanna ecosystems. Our results serve as a benchmark for future studies aiming to generate accurate biomass maps and provide baseline data for efficient management of fire and predicted climate change impacts on tropical savanna ecosystems