A Novel de Novo Mutation in the CD40 Ligand Gene in a Patient With a Mild X-Linked Hyper-IgM Phenotype Initially Diagnosed as CVID: New Aspects of Old Diseases.

Mutations in the CD40 ligand (CD40L) gene (CD40LG) lead to X-linked hyper-IgM syndrome (X-HIGM), which is a primary immunodeficiency (PID) characterized by decreased serum levels of IgG and IgA and normal or elevated IgM levels. Although most X-HIGM patients become symptomatic during the first or second year of life, during which they exhibit recurrent infections, some patients exhibit mild phenotypes, which are usually associated with hypomorphic mutations that do not abrogate protein expression or function. Here, we describe a 28-year-old man who initially presented with recurrent infections since the age of 7 years, when he exhibited meningitis caused by Cryptococcus neoformans. The patient had no family history of immunodeficiency, and based on clinical and laboratory presentation, he was initially diagnosed with common variable immunodeficiency (CVID). In subsequent years, he displayed several sporadic episodes of infection, including pneumonia, pharyngotonsillitis, acute otitis media, rhinosinusitis, fungal dermatosis, and intestinal helminthiasis. The evaluation of CD40L expression on the surface of activated CD3+CD4+ T cells from the patient showed decreased expression of CD40L. Genetic analysis revealed a novel de novo mutation consisting of a 6-nucleotide insertion in exon 1 of CD40LG, which confirmed the diagnosis of X-HIGM. In this report, we describe a novel mutation in the CD40L gene and highlight the complexities of PID diagnosis in light of atypical phenotypes and hypomorphic mutations as well as the importance of the differential diagnosis of PIDs.

Comparative Efficiency and Impact on the Activity of Blood Neutrophils Isolated by Percoll, Ficoll and Spontaneous Sedimentation Methods.

Studies on the role of cells in physiological and pathological processes generally require isolation of some populations, such as neutrophils. In the literature, several methods used for isolating neutrophils are described; however, there is no consensus on the best technique to be used in cell functional studies. The present study compares the efficiency and impact on the chemotactic and phagocytic activity of neutrophils isolated from blood by three different methods: Percoll and Ficoll density centrifugation gradients and spontaneous sedimentation technique. The neutrophil chemotaxis, stimulated with lipopolysaccharide (LPS), autologous serum or homologous serum, was determined by using Boyden chambers. The phagocytic capacity was assessed by ingestion of zimosan particles, and digestion phase was analyzed by nitroblue tetrazolium test (NBT). The results obtained from neutrophil isolation by Percoll and Ficoll density gradients, as compared to spontaneous sedimentation technique, showed similar degrees of cell yields and higher purity; however, these methods affected neutrophil responsiveness, accompanied by elevated chemotaxis and reduced chemotactic capacity to respond to subsequent stimulation. Neutrophil isolation by spontaneous sedimentation, in contrast, did not affect cellular activity and resulted in cell preparation with high number of neutrophils. Although neutrophil phagocytosis results were similar between the different methods, digestion phase of phagocytosis was significantly enhanced after LPS-stimulation, only in the neutrophils isolated by spontaneous sedimentation technique. In conclusion, the present study shows that isolation of blood neutrophils by the spontaneous sedimentation technique is appropriate for the assessment of cellular activity, since it neither primes or activates the neutrophils nor does it affect their functional responsiveness.

Chemotactic and Phagocytic Activity of Blood Neutrophils in Allergic Asthma.

Allergic asthma is a chronic inflammatory airway disease, and has been considered a T helper-2-biased response. Studies suggest that neutrophils may be associated with exacerbation and asthma severity. We sought to evaluate the chemotactic activity and phagocytic capacity by peripheral blood neutrophils from individuals with controlled and uncontrolled allergic asthma, and compare the results with non-asthmatic controls groups. Blood neutrophils were isolated from 95 patients: 24 with controlled asthma, 24 uncontrolled asthma, 24 healthy subjects and 23 patients with IgE-mediated allergies other than asthma. The neutrophil chemotaxis, stimulated with LPS, autologous serum or homologous serum, was determined using Boyden chambers. The phagocytic capacity was assessed by ingestion of zimosan particles, and digestion phase was analyzed by NBT test. The phagocytic digestion phase and chemotaxis by neutrophils from asthmatic patients was higher than in non-asthmatic controls (p < 0.05). Autologous serum-induced neutrophil chemotaxis in patients with uncontrolled asthma was greater (p < 0.05) than in other study groups. The ingestion phase of phagocytosis showed similar values in asthmatics and non-asthmatics. We conclude that the blood neutrophil from controlled and uncontrolled asthmatic patients exhibit activation markers, particularly phagocytic digestion and chemotactic activities.

Interleukin-10 may protect against progressing injury during the acute phase of ischemic stroke / Interleucinas 1B, 2 e 10 e prognostico neurologico durante a fase aguda do AVC isquemico

Atherosclerosis is an inflammatory disease, and ischemic stroke is one of its most common and devastating manifestations. Proinflammatory cytokines play a key role in the progression of the irreversible ischemic lesions. The presence of anti-inflammatory mediators may prevent secondary ischemic injury. Objectives 1) To assess the relationship between stroke severity and the serum levels of IL-1β, IL-2, and IL-10; and 2) To analyze the neurological outcome after 72 h of ischemic stroke onset and expression of interleukins. Method We measured the serum levels of IL-1β, IL-2, and IL-10 in 26 patients with acute stroke. Neurological impairment was scored using the National Institute of Health Stroke Scale within the first 72 h after stroke onset. Thirty healthy subjects were analyzed as controls. Results Patients with IL-10 <925.0 pg/mL presented with neurological deterioration within the first 72 h. Conclusion IL-10 may protect against ischemic injury during the acute phase of stroke. .

Aterosclerose é considerada um doença inflamatória e o acidente vascular cerebral (AVC) isquêmico uma de suas principais manifestações. Citocinas pró-inflamatórias exercem importante função na progressão para uma lesão isquêmica irreversível. A presença de mediadores anti-inflamatórios age prevenindo a lesão isquêmica secundária. Objetivos 1) Avaliar a relação entre gravidade do AVC e níveis de IL-1β, IL-2 e IL-10; 2) Avaliar a relação entre prognóstico neurológico nas primeiras 72 horas do AVC e o nível destas citocinas. Método Mensuramos os níveis de IL-1β, IL-2 e IL-10 de 26 pacientes com AVC isquêmico. O comprometimento neurológico foi avaliado através da escala do National Institute of Health nas primeiras 72 horas do AVC. Trinta indivíduos saudáveis foram usados como controles. Resultados Pacientes com IL-10 <925,0 pg/mL apresentaram deterioração neurológica nas primeiras 72 horas após o início do AVC. Conclusão IL-10 pode apresentar um efeito protetor contra a progresso da lesão isquêmica durante a fase aguda do AVC. .

Interleukin-10 may protect against progressing injury during the acute phase of ischemic stroke.

UNLABELLED: Atherosclerosis is an inflammatory disease, and ischemic stroke is one of its most common and devastating manifestations. Proinflammatory cytokines play a key role in the progression of the irreversible ischemic lesions. The presence of anti-inflammatory mediators may prevent secondary ischemic injury. OBJECTIVES: 1) To assess the relationship between stroke severity and the serum levels of IL-1ß, IL-2, and IL-10; and 2) To analyze the neurological outcome after 72 h of ischemic stroke onset and expression of interleukins. METHOD: We measured the serum levels of IL-1ß, IL-2, and IL-10 in 26 patients with acute stroke. Neurological impairment was scored using the National Institute of Health Stroke Scale within the first 72 h after stroke onset. Thirty healthy subjects were analyzed as controls. RESULTS: Patients with IL-10 <925.0 pg/mL presented with neurological deterioration within the first 72 h. CONCLUSION: IL-10 may protect against ischemic injury during the acute phase of stroke.

Componentes C3 e C4 do sistema complemento como biomarcadores no diagnóstico de asma atópica intermitente / C3 and C4 complement system components as biomarkers in the intermittent atopic asthma diagnosis

OBJETIVO: Analisar os componentes séricos C3 e C4 do sistema complemento como possíveis biomarcadores de asma atópica intermitente. MÉTODOS: Determinação dos níveis séricos dos componentes C3 e C4 do complemento em 70 crianças com história de "chiado no peito” entre 3 e 14 anos. Após 2 anos de acompanhamento ambulatorial, seguindo-se critérios de inclusão e exclusão, as crianças foram divididas em 2 grupos: 40 crianças com asma atópica intermitente e 30 crianças sem asma. Não houve uso de corticosteroides inalatórios ou sistêmicos ou de broncodilatadores de ação prolongada em nenhum dos grupos. Os dois grupos apresentaram faixas etárias semelhantes, comparadas pelo teste t de Student. Os resultados dos componentes C3 e C4 mostraram distribuição normal e foram então comparados utilizando-se o teste t de Student, considerando-se significante quando p < 0,05. RESULTADOS: Os valores observados no grupo de crianças portadoras de asma atópica intermitente mostraram aumentos significativos para: C3 em 85,0% das crianças; C4 em 87,5%; C3 e C4 em 72,5%; C3 ou C4 em 97,5%, quando comparados aos valores observados das crianças sem asma e da mesma faixa etária. CONCLUSÃO: Observamos um aumento dos valores séricos dos componentes C3 e/ou C4 do sistema complemento na maioria das crianças estudadas portadoras de asma atópica intermitente, em comparação aos valores de crianças sem asma, da mesma faixa etária. Concluímos que a presença de valores aumentados dos componentes C3 e/ou C4 do complemento possa representar um biomarcador no diagnóstico de asma atópica intermitente.

OBJECTIVE: To analyze serum C3 and C4 complement system components with a view to their possible utility as biomarkers of intermittent atopic asthma. METHODS: Serum levels of the C3 and C4 complement components were assayed in 70 children aged from 3 to 14 years and with a history of "wheezy chest.” After 2 years' outpatients follow-up and after application of inclusion and exclusion criteria, the children were divided into two groups: 40 children with intermittent atopic asthma and 30 children without asthma. None of the children in either group were treated with inhaled or systemic corticosteroids or long-acting bronchodilators. The two groups had similar ages according to Student's t test. The C3 and C4 component test results followed a normal distribution and were therefore compared using Student's t test with significance set at p < 0.05. RESULTS: The results for the group with intermittent atopic asthma were significantly elevated for C3 in 85.0% of the children, for C4 in 87.5% of the children, for both C3 and C4 in 72.5% of the children, and for either C3 or C4 in 97.5% of the children, when compared with the results for the children without asthma from the same age group. CONCLUSION: We observed an increase in the serum levels of the C3 and/or C4 components of the complement system in the majority of the patients with intermittent atopic asthma studied here, when compared with the results for children in the same age group without asthma. We conclude that the presence of elevated C3 and/or C4 complement components could represent a biomarker for diagnosis of intermittent atopic asthma.

C3 and C4 complement system components as biomarkers in the intermittent atopic asthma diagnosis.

OBJECTIVE: To analyze serum C3 and C4 complement system components with a view to their possible utility as biomarkers of intermittent atopic asthma. METHODS: Serum levels of the C3 and C4 complement components were assayed in 70 children aged from 3 to 14 years and with a history of "wheezy chest." After 2 years' outpatients follow-up and after application of inclusion and exclusion criteria, the children were divided into two groups: 40 children with intermittent atopic asthma and 30 children without asthma. None of the children in either group were treated with inhaled or systemic corticosteroids or long-acting bronchodilators. The two groups had similar ages according to Student's t test. The C3 and C4 component test results followed a normal distribution and were therefore compared using Student's t test with significance set at p < 0.05. RESULTS: The results for the group with intermittent atopic asthma were significantly elevated for C3 in 85.0% of the children, for C4 in 87.5% of the children, for both C3 and C4 in 72.5% of the children, and for either C3 or C4 in 97.5% of the children, when compared with the results for the children without asthma from the same age group. CONCLUSIONS: We observed an increase in the serum levels of the C3 and/or C4 components of the complement system in the majority of the patients with intermittent atopic asthma studied here, when compared with the results for children in the same age group without asthma. We conclude that the presence of elevated C3 and/or C4 complement components could represent a biomarker for diagnosis of intermittent atopic asthma.

Caracterização da resposta a testes cutâneos de hipersensibilidade tardia em pacientes internados na UTI / Characterization of the response to the delayed hypersensitivity: skin tests in ICU patients

Infecções hospitalares estão entre as principais complicações associadas a óbito em Unidade de Terapia Intensiva(UTI). Entretanto, existem poucas ferramentas validadas em UTI para tentar caracterizar o risco de tais complicações. Objetivo: Caracterizar a resposta a testes cutâneos de hipersensibilidade tardia no momento da admissão de pacientes em UTI, relacionando-a ao desenvolvimento de infecção hospitalar. Pacientes e métodos: Foram analisadas as respostas dos testes cutâneos (pápulas formadas) para quatro antígenos: PPD, candidina, tricofitina e estreptoquinase em 78 pacientes, à admissão em UTI. Os pacientes foram divididos em três grupos: A) sem infecção na admissão e durante a internação; B)sem infecção na admissão e que desenvolveram infecção durante a internação; C) infecção diagnosticada na admissão. Foram ainda divididos em: eutróficos, obesos e desnutridos. Resultados: Tanto pacientes que desenvolveram infecção na UTI (24 pacientes) quanto aqueles que já apresentavam infecção à admissão (15 pacientes) apresentaram menor positividade dos testes ao PPD (1,75 e 0,53mm) e à candidina (1,45 e 1,06mm), quando comparados a 34 pacientes que nãodesenvolveram infecção (4,97 para PPD e 4,74mm para candidina)(p<0,05). Observou-se ainda que os 40 desnutridos apresentaram menor positividade à candidina (1,91mm) quando comparados aos 21 eutróficos (3,17mm) (p<0,05). Conclusão: Observamos que pacientes com diagnóstico de infecção à internação em UTI e os que evoluíram para infecção na UTI apresentaram uma menor resposta aos testes cutâneos de hipersensibilidade tardia ao PPD e à candidina. Acreditamos que a aplicação dos testes cutâneos possa ser uma ferramenta útil na avaliação de risco de infecção hospitalar em UTI.

The hospital infections are among the major complications associated with death in the Intensive Care Unit (ICU). However, there are few validated tools in the ICU to try to characterize the risk of such complications. Objective: To characterize the response to skin tests for delayed hypersensitivity at the time of admission of patients inthe ICU and its relation to the development of nosocomial infection. Patients and Methods: We analyzed the responses of skin tests (papules formed) to four antigens: PPD, candidina, trichophytinand streptokinase in 78 patients at the ICU admission. Patients were divided into three groups: A) no infection at admission and during hospitalization; B) without infection on admission and who developed infections during hospitalization; C) infection diagnosed on admission. Patients were further divided into: normal weight, obese and malnourished. Results: The patients that developed infections in the ICU(24 patients) and those that already had infection on admission(15 patients) had lower positivity to PPD (1.75 and 0.53mm) and candidina tests (1.45 and 1.06mm), when they were compared to 34 patients without infection (4.97 for PPD and 4.74mm for candidina) (p<0.05). It was also observed that the 40 malnourished patients had lower positivity for candidina (1.91 mm) when they were compared to 21 normal weight(3,17mm) (p<0.05). Conclusion: We found that patients with a diagnosis of infection at admission in the ICU and who progressed to infection in the ICU had a lower response to skin tests for delayed hypersensitivity to PPD and candidina. We believe that the application of skin tests may be a useful tool in assessing risk of nosocomial infection in ICU.

Crioglobulinemia na esclerose sistêmica / Cryoglobulinemia in sistemic sclerosis

Os autores pesquisaram a presença de crioglobulinemia em 26 pacientes com Esclerose Sistêmica, encontrando-a positiva em 12 (46,23%). A incidência de acometimento pulmonar é mais freqüente nos indivíduos com crioglobulinemia