Expansion of FOXP3-positive CD4+CD25+ T cells associated with disease activity in atopic dermatitis.

BACKGROUND: FOXP3-positive CD4+CD25+ T cells are known to have an immunoregulatory function by means of preventing T-cell reactivity to both self- and non-self-antigens. However, the role of these cells in the pathogenesis of allergic diseases is not clear. OBJECTIVE: To evaluate the quantity and quality of circulating FOXP3-positive T cells in patients with atopic dermatitis (AD). METHODS: Peripheral blood mononuclear cells were isolated from 35 AD patients (mean [SD] age, 27.1 [7.5] years) and 36 controls (mean [SD] age, 27.5 [10.0] years). Cellular FOXP3 expression was analyzed using flow cytometry. Characteristics of FOXP3-positive T cells were evaluated with respect to cytokine production capability and suppressive function. RESULTS: Frequencies of circulating FOXP3+CD25+ cells in the CD4+ T-cell population of AD patients were significantly higher than those in controls (mean [SD], 7.4% [4.6%] vs 4.5% [1.3%]; P = .002) and correlated with their Scoring Atopic Dermatitis (SCORAD) scores (r = 0.74, P = .008) and peripheral blood eosinophil counts (r = 0.72, P < .001). In the patients whose samples were analyzed at intervals of 1 to 2 months, frequencies of FOXP3-positive T cells were decreased as their skin lesions improved, regardless of medicines used. FOXP3-positive CD4+ T cells from patients, as well as those from controls, showed little capability to synthesize interferon gamma and interleukin 4. No differences were found in suppression abilities of CD4+CD25+ T cells between AD patients and controls. CONCLUSIONS: Our data suggest that dynamic fluctuation in numbers of circulating FOXP3-positive regulatory T cells might contribute to the pathogenesis of AD.

Developmental changes of FOXP3-expressing CD4+CD25+ regulatory T cells and their impairment in patients with FOXP3 gene mutations.

FOXP3 is required for the generation and function of CD4(+)CD25(+) regulatory T (Treg) cells. To elucidate the biological role of Treg cells, we used a monoclonal anti-FOXP3 antibody to examine the frequencies of Treg cells during child development. The percentages of CD4(+)CD25(+)FOXP3(+) T cells were constant shortly from after birth through adulthood. CD4(+)CD25(+)FOXP3(+) T cells in cord blood showed the naive CD45RA(+)CD45RO(-) phenotype, whereas adult CD4(+)CD25(+)FOXP3(+) T cells expressed mostly the memory CD45RA(-)CD45RO(+) phenotype. The age-dependent dominance of memory CD4(+)CD25(+)FOXP3(+) T cells implies functional differences between naive and memory Treg cells. Notably, four patients with FOXP3 gene mutations revealed a paucity of CD4(+)CD25(+)FOXP3(+) T cells. Importantly, one patient with a frame shift mutation, who showed typical symptoms of IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked), exhibited marked T cell activation, whereas others with missense mutations, who were clinically milder, did not. This observation suggests a possible genotype-phenotype correlation in IPEX.

Safety and usefulness of a novel eMotion electric mesh nebulizer in children with asthma.

BACKGROUND: A new electronic mesh nebulizer, eMotion is known to have higher performance compared to conventional nebulizers. However, there are some concerns about whether too much delivered dose might cause side effects with higher frequency. METHODS: To evaluate the safety and usefulness of the nebulizer, we measured changes in heart rates and lung functions of 73 asthmatic children when they inhaled 1 microg/kg of procaterol with eMotion or a conventional nebulizer, Junior BOY. RESULTS: In 34 children with mild asthma exacerbation, physical findings, lung function and transcutaneous oxygen saturation levels were improved after inhalation using both nebulizers. No adverse effects including significant increase of heart rate were found. Improvements in the rates of the parameters were comparable. When response to beta2-agonist inhalation was checked in 39 children in stable condition, similar degrees of improvement in lung function were observed, and heart rates did not change after inhalation with either nebulizers. CONCLUSIONS: Safety and efficacy was comparable between eMotion and a conventional nebulizer when it was used to administer beta2-agonists in asthmatic children. However, from the fact that eMotion needs only 3-4 minutes to inhale 2 mL solution, eMotion could be more useful for most children who usually do not prefer longer inhalation time with conventional compressor nebulizers.

Theophylline metabolism in acute asthma with MxA-indicated viral infection.

BACKGROUND: Although viral infection might alter theophylline metabolism in acute asthma, there are some difficulties in detecting infection due to various kinds of viruses in a clinical setting. METHODS: To evaluate the usefulness of assessment of MxA protein in acute asthma exacerbated by viral infection, MxA protein expression in lymphocytes was assayed by flow cytometric analysis in whole peripheral blood in 21 children (aged 0-6 years) receiving continuous theophylline infusion for management of asthma attack. Serum theophylline levels were measured at 24 and 72 h after initiating theophylline infusion. RESULTS: At the beginning of theophylline infusion, 11 children had increased expression of MxA protein, indicating viral infected states. After 24 h continuous infusion, there were no differences in theophylline levels between MxA-negative and MxA-positive groups. After 72 h infusion, the mean theophylline level of MxA-positive children was significantly higher than that of MxA-negative children (9.7 +/- 2.2 microg/mL vs 7.3 +/- 1.6 microg/mL). The ratio of theophylline clearance at 72 h to that at 24 h in the MxA-positive group was significantly lower than that of the MxA-negative group (1.1 +/- 0.2 vs 1.4 +/- 0.1). CONCLUSIONS: Viral infection appeared to affect theophylline metabolism. Flow cytometric assay of lymphoid MxA protein expression in whole blood is an easy and useful method of evaluating viral infection in acute asthma exacerbation.

End-stage renal failure in a child with X-linked ichthyosis.

We describe an 8-year-old boy who presented with steroid-resistant nephrotic syndrome (SRNS) associated with X-linked ichthyosis (XLI). At birth, the patient exhibited scaly skin, cryptorchidism, and steroid sulfatase (STS) deficiency. DNA analysis showed deletion of exons 1-10 of the STS gene. Proteinuria developed at 6 years and was resistant to steroid therapy. Kidney biopsy findings prior to steroid therapy were compatible with minimal change nephrotic syndrome. By immunofluorescence, glomerular basement membranes exhibited diffuse linear staining for the alpha5 chain of collagen IV, making X-linked Alport syndrome an unlikely explanation for the association of SRNS and ichthyosis. Despite immunosuppressive therapy together with oral prednisolone, no clinical response was achieved. He rapidly reached end-stage renal failure and finally underwent renal transplantation. We propose that SRNS should be considered as one of the highly variable phenotypes associated with XLI.