Establishing a cut-off for the serum levels of specific IgE to milk and its components for cow's milk allergy: results from a specific population.

BACKGROUND: Cow's milk allergy diagnosis many times requires double-blind placebo-controlled food challenge (DBPCFC), which presents high accuracy but involves risks, specifically in infants and anaphylactic patients. The identification of the cut-off values for specific IgE to milk or its components would contribute to cow's milk allergy (CMA) diagnosis. The aim of this study was to compare discriminating concentration of a cow's milk specific IgE and its fractions (α-lactoalbumin, ß-lactoglobulin, casein) in children for the CMA diagnosis. METHODS: this study included 123 patients (M:F=1.3:1) median age at diagnosis=1.91 years, (3.5m to 13.21y) with CMA diagnosis via DBPCFC (n=26), proven anaphylaxis due to cow's milk (n=46) or a suggestive clinical history associated with a positive skin prick test (n=51) and open oral food challenge. The control group included 61 patients (1 male:1.1 female) ages ranging from 0.66 to 16.7 years (median=6.83 years). Receiver operator characteristics (ROC) curves were constructed to determine the best cut-offs that guarantees high specificity (>95%) for cow's milk and its components. RESULTS: considering 98% specificity, cut-off points were: 3.06 kU/L for cow's milk, 2.06 kU/L for α-lactalbumin, 1.85 kU/L for ß-lactoglobulin and 1.47kU/L for casein. The best ROC curve (area under the curve=0.929) was obtained evaluating cow's milk. CONCLUSION: this study showed that the cut-off point detected for whole cow's milk revealed a better discriminatory capacity for CMA diagnosis without the necessity of the milk components testing.

Reduced frequency of CD4(+)CD25(HIGH)FOXP3(+) cells and diminished FOXP3 expression in patients with Common Variable Immunodeficiency: a link to autoimmunity?

Common Variable Immunodeficiency (CVID) is a primary immunodeficiency disease characterized by defective immunoglobulin production and often associated with autoimmunity. We used flow cytometry to analyze CD4(+)CD25(HIGH)FOXP3(+) T regulatory (Treg) cells and ask whether perturbations in their frequency in peripheral blood could underlie the high incidence of autoimmune disorders in CVID patients. In this study, we report for the first time that CVID patients with autoimmune disease have a significantly reduced frequency of CD4(+)CD25(HIGH)FOXP3(+) cells in their peripheral blood accompanied by a decreased intensity of FOXP3 expression. Notably, although CVID patients in whom autoimmunity was not diagnosed had a reduced frequency of CD4(+)CD25(HIGH)FOXP3(+) cells, FOXP3 expression levels did not differ from those in healthy controls. In conclusion, these data suggest compromised homeostasis of CD4(+)CD25(HIGH)FOXP3(+) cells in a subset of CVID patients with autoimmunity, and may implicate Treg cells in pathological mechanisms of CVID.

Occupational asthma caused by Ipe (Tabebuia spp) dust.

BACKGROUND: Ipe is a resistant hardwood that contains naphtoquinones. It is easily found and frequently used in South and Central America. Naphtoquinones are skin sensitizers. OBJECTIVE: To describe a case of occupational asthma related to Ipe wood dust. METHODS: The patient was submitted to a clinical evaluation consisting of a respiratory symptom questionnaire, occupational history, serial measurements of lung function by spirometry, skin prick tests, patch tests, specific IgE and specific bronchial provocation tests to Ipe dust. RESULTS: Serial lung function measurements showed sustained regression of obstruction following removal from exposure. Skin prick tests, but not patch tests, were positive to Ipe, and a specific bronchial challenge showed a late asthmatic reaction. Specific IgE search was negative. CONCLUSIONS: Exposure to Ipe wood dust can lead to occupational asthma. The underlying mechanism should be investigated.

Alterações da imunidade celular associada à patogênese da imunodeficiência Comun variável / Changes in cellular immunity asssociated with the pathogenisis of common variable immunodeficiency

Objetivo: Avaliação da morte celular por ativação em linfócitos T de pacientes com imunodeficiência comum variável (CVID) e de outros parâmetros da resposta imune. Métodos: Células mononucleares obtidas a partir de sangue periférico (PBMC) de 32 pacientes com CVID e 32 indivíduos normais foram utilizadas para o estudo da expressão de CD40L, linfoproliferação e apoptose, Para a análise de marcadores de ativação (CD25 e CD69) e de interação entre células T e B (CD70) PBMC foram estimuladas por diferentes tempos (24, 48, 72 e 96 horas), Os sobrenadantes de cultura foram utilizados para quantificação de citocinas (IL-2, IL-4, IL-5 e IFN-y) por ELISA. Todos os testes laboratoriais foram aplicados no grupo controle de voluntários sadios. Os resultados foram analisados utilizando testes de diferença de proporções, ANOV A, Kruskal-Wallis e a prova de Mann-Whitney. Resultados: O grupo de pacientes com CVID demonstrou aumento percentual de linfócitos CD3/CD4 que sofreram apoptose em relação ao grupo controle (p< (Au) pacientes. destes anticorpos por mediada e celular resposta da prejuízo conseqüente com Th2, citocinas de diminuída síntese além CD70, CD69 CD25, CD40L, expressão circulantes, B T células nas decréscimo pelo responsável seja fenômeno este que sugere ativadas morte aumento O Conclusões: normais. indivíduos grupo o comparados quando CVID pacientes.

Lysine-vasopressin in the evaluation of the hypothalamic-pituitary-adrenal axis in children with allergic rhinitis treated with intranasal beclomethasone dipropionate or oral prednisone.

One of the complications of steroid therapy is the hypothalamic-pituitary-adrenal (HPA) axis' suppression, particularly in children where this can lead to growth suppression and other well known complications. Although there are a large number of studies on suppression of the HPA axis with the use of topical steroids, the subject is still controversial. We measured the HPA axis function in 3 groups of allergic children treated with: 1) intranasal beclomethasone dipropionate (BDP) 400 micrograms/day for 4 weeks or 2) BDP 800 micrograms/day for 4 weeks and 3) oral prednisone, 1 mg/kg/day for 2 weeks. The HPA response was obtained after lysine-vasopressin (LVP) stimulation. LVP acts on the pituitary or hypothalamus level, stimulating the whole axis. Peripheral blood samples through an intravenous line were obtained for serum cortisol measurement at zero, 30, 60, and 90 minutes after the intravenous injection of LVP, before and after the treatment period. Our results showed no suppression of the HPA axis in children medicated with BDP at either 400 micrograms/day or 800 micrograms/day. On the other hand, there was a suppression of the HPA axis after prednisone treatment (p < 0.05). During the LVP test some side effects, possibly due to systemic vasoconstriction, were noted such as abdominal pain, nausea and vomiting, and transient hypertension. In conclusion, intranasal BDP at the dose of 400 or 800 micrograms/day during 4 weeks did not induce HPA axis suppression. The LVP test is efficient to demonstrate HPA hypofunction or suppression and it produced only mild to moderate transient side effects. However, due to the side effects observed, a safer test such as urinary free cortisol (24 hours), should be used in the investigation of the HPA axis.

Targeted gene disruption of murine CD7.

CD7 is a 40 kDa type I transmembrane glycoprotein member of the Ig superfamily. CD7 is a marker of mature human T cells and NK cells, and is expressed early in their development. Cross-linking CD7 positively modulates T cell and NK cell activity as measured by calcium fluxes, expression of adhesion molecules, cytokine secretion and proliferation. CD7 associates directly with phosphoinositol 3'-kinase, and CD7 ligation induces production of D-3 phosphoinositides and tyrosine phosphorylation. Severe combined immunodeficiency has been associated with a lack of lymphocyte surface CD7. The CD7 ligand is unknown. The murine CD7 homolog is encoded by a single gene on chromosome 11. In order to characterize the role of CD7 in lymphocyte development and function we have eliminated the CD7 gene by targeted disruption. CD7-deficient mice display normal histology of thymus and spleen, normal lymphocyte populations in primary and secondary lymphoid tissues, and normal serum Ig levels. Specific antibody responses after immunization with T-dependent and T-independent antigens are equivalent in wild-type and CD7 knockout mice. CD7-deficient lymphocytes respond normally to T cell mitogenic and allogeneic stimuli, and display normal NK cell cytotoxicity.