Changes in skin reactivity and associated factors in patients sensitized to house dust mites after 1 year of allergen-specific immunotherapy

BACKGROUND: Allergen-specific immunotherapy (SIT) can significantly improve symptoms and reduce the need for symptomatic medication. OBJECTIVE: The aim of this study was to investigate changes in skin reactivity to house dust mites (HDMs) as an immunologic response and associated factors after 1 year of immunotherapy. METHODS: A total of 80 patients with allergic airway diseases who received subcutaneous SIT with HDMs from 2009 to 2014 were evaluated. The investigated parameters were basic demographic characteristics, skin reactivity and specific IgE for HDM, serum total IgE level, blood eosinophil counts, and medication score. RESULTS: The mean levels of skin reactivity to HDMs, blood eosinophil counts, and medication scores after 1 year were significantly reduced from baseline. In univariate comparison of the changes in skin reactivity to HDMs, age ≤30 years, HDMs only as target of immunotherapy, and high initial skin reactivity (≥2) to HDMs were significantly associated with the reduction in skin test reactivity. In multivariate analysis, high initial skin reactivity and HDMs only as target allergens were significantly associated with changes in skin reactivity to HDMs. In the receiver operating characteristic curve of the initial mean skin reactivity to HDMs for more than 50% reduction, the optimal cutoff value was 2.14. CONCLUSION: This study showed significant reductions in allergen skin reactivity to HDMs after 1 year of immunotherapy in patients sensitized to HDMs. The extent of initial allergen skin reactivity and only HDMs as target allergen were important predictive factors for changes in skin reactivity.

Modificaciones de parámetros clínicos, celulares y moleculares al cabo de un año de inmunoterapia alérgeno específica / Parameters modified of allergy after immunotherapy

Antecedentes. En general, los pacientes alérgicos, después de un año de inmunoterapia (IT), muestran mejoría en la frecuencia e intensidad de los síntomas. Objetivo. Demostrar que la IT tiene efectos moduladores sobre parámetros clínicos, celulares y moleculares de alergia de acuerdo con las edades. Metodología. Se incluyeron 81 pacientes alérgicos asmáticos: 28 infantes, 36 niños, 17 adultos y 27 controles. En los niños y jóvenes se evaluó el pico flujo espiratorio (PEF), reactividad cutánea, se registró eosinofilia sanguínea y de exudado de mucosa nasal, liberación de enzima ß-hexosaminidase (ß-H) de basófilos, proliferación de PBMC estimuladas con alérgeno específico o PHA; se cuantificaron las concentraciones de IgE, IL-13 y sCD23 en sueros y de IFN-γ en sobrenadantes de cultivos de PBMC. Resultados. Niños y adultos sin IT empeoraron sus reducidos valores de PEF. Niños y adultos después de IT mostraron incremento en los volúmenes de PEF (p<0,0001). Todos los grupos con IT redujeron la reactividad cutánea (p<0,0001, p<0,0001 y p<0,02) y la liberación de B-H de basófilos desafiados con el alérgeno específico (p<0,0001, p<0,0001 y p<0,003). Niños y adultos con IT observaron disminución en los niveles de IgE, ambos p<0,05, y redujeron los niveles de células eosinófilos nasales (p<0,0001 y p<0,01). Solamente los niños tratados con IT redujeron los niveles de células eosinófilas sanguíneas (p<0,0001). Las PBMC de infantes y niños con IT disminuyeron los índices de proliferación desafiadas con el alérgeno específico, ambos p<0,05. Los pacientes alérgicos observaron menores niveles de IFN-γ (p<0,02) y más altos niveles de IL-13 (p<0,05) y sCD23 (p<0,001) que los hallados en controles. Conclusiones. La IT demostró efectividad terapéutica en pacientes asmáticos y cambios en parámetros clínicos celulares y moleculares. Algunos de esos parámetros fueron indicadores de la evolución de la enfermedad y ellos fueron diferentes de acuerdo con las edades(AU)

Background: Most allergic patients, after a year of specific immunotherapy (SIT), show improvement in the frequency and intensity of the symptoms. Objective. The objective was to demonstrate that specific immunotherapy has modulating effects on clinical, cellular and molecular parameters, of allergy. Methods. The study included 81 asthmatic allergic patients and 27 healthy controls from 2 to 50 years of age. Peak expiratory flow, skin reactivity, blood and nasal smear eosinophilia was conducted. ß- hexosaminidase enzyme (B-H) release assays and Peripheral Blood Mononuclear Cells cultures stimulated with specific allergens, were realized. Total IgE, sCD23 and IL-13 were measured in serum and IFN- γ, in culture supernatants. Results. In all the cases a reduction in the frequency and intensity of the asthma attacks and a decrease in medical consultations and antiallergic drugs consumption were observed. The patients without SIT diminished low PEF values. Children and adult people with SIT increased the volumes of peak expiratory flow, (p<0.0001). Skin reactivity was reduced in all the SIT groups'. Skin reactivity were p < 0.0001, p<0.0001 y p<0.02) respectively, and B-H released were p<0.0001, p<0.0001 y p<0.003) to each group. The infants without SIT increased IgE levels. Nasal smear eosinophilia fell from children and adults, p < 0.0001. In Infants and children with SIT, the cellular expansion by the allergen was reduced (p<0.05). In allergic patients IFN-γ values were lower than controls, (p < 0.02). IFN -γ synthesis did not vary after a year of allergen -specific immunotherapy. Allergic patients observed higher serum levels of IL-13 (p<0.05) and sCD23 (p<0.001) than controls. Conclusions. SIT after a year demonstrated therapeutic effectiveness in asthmatic patients with changes in multiple parameters: clinical, cellular and molecular. (AU)

Perfil clínico e imunológico das manifestações alérgicas respiratórias em pacientes infectados com HTLV-1 / Clinical and immunoligical profile of respiratory allergic manifestations in patients infected with HTLV-1

Objective: To review the main characteristics of HTLV-1 infection and its influence upon the immune response type 2 in atopic individuals. Methods: This review was made by means of bibliographic rising of data files obtained through Medline and Lilacs from 1980 to 2005. Results: The HTLV-1 is a retrovirus which functionally alters the cells of the immune system. The antiviral immune response and its modulatory responses are mainly regulated by means of the tax gene. The HTLV-1 has a tropism for CD4+ T-lymphocite, promotes proliferation of this group of cells spontaneously and increases IFN production. The HTLV-1 infection, polarizes the immune response towards a type 1 response and reduces IL4 production, IgE and the immediate skin reactivity. The allergic and parasitic diseases are predominantly characterized by immunologic manifestations type 2, enhanced IL4 and activation of mast cells and eosinophils. The HTLV-1 infected individuals show a strong type 1 immune response therefore are susceptible to acquire helminthic infestation, but may inhibit allergic manifestations. Conclusions: The immune response against HTLV-1 with increased IFN production is unable to eliminate the virus, but promotes enough disturbances to suppress immune response type 2 in atopic individuals

Objetivos: Revisar as principais características da infecção pelo HTLV-1 e sua influência sobre a resposta imune tipo 2 em indivíduos atópicos. Métodos: A revisão foi feita a partir de estudos identificados em base de dados MedLine e Lilacs no período de 1980 a 2005. Resultados: O vírus HTLV-1 é um retrovírus que altera funcionalmente células importantes do sistema imune. A resposta imune antiviral e suas conseqüências moduladoras são reguladas principalmente através do gene viral tax. O HTLV-1 tem tropismo por linfócitos T CD4+ e CD8+, promove a proliferação espontânea destas células e a elevada produção de IFN. Na infecção pelo HTLV-1, a polarização Th1 da resposta imune reduz a produção de IL4, IgE e a reatividade cutânea imediata. As doenças alérgicas e parasitárias caracterizam-se por manifestações imunológicas predominantemente do tipo 2 com elevação de IL4 e ativação de mastócitos e eosinófilos. Indivíduos infectados com o vírus HTLV-1 por apresentarem forte resposta imune do tipo 1 são mais susceptíveis a infestações por helmintos mas podem atenuar as manifestações alérgicas. Conclusão: A resposta imune contra o HTLV-1 com elevada produção de IFN é ineficaz para a eliminação do vírus, mas promove alteração suficiente para supressão da resposta imune tipo 2 em um subgrupo de indivíduos atópicos

Linkage analysis between gene marker of chromosome 11q13, and skin reactivity to common inhalant allergens and bronchial responsiveness in sib-pairs with probands of asthmatic children / 천식및알레르기

BACKGROUND: Increased IgE antibody responses to inhalant allergens and bronchial hyperresponsiveness are important phenotypes in development of asthma. Although heredity reported to be important in expression of these phenotypes in twin and family studies, genetic factor(s) controlling these phenotypes is unknown. OBJECTIVE: To evaluate whether genetic factor in chromosome 11q13 may control the expression of IgE responses to common inhalant allergens and bronchial hyperresponsiveness, linkage analysis between these phenotypes and gene marker of chromosome 11q13 was investigated. MATERIALS AND METHODS: The phenotyping and genotyping using microsatellite marker (D11S97) were performed in 77 probands with bronchial asthma and 80 their sibs. The linkage analysis between these phenotypes and the genotype was evaluated by affected or quantitative trait locus (QTL) sib-pair analysis. RESULTS: Positive skin test responses to inhalant allergens were 55/77(71.4%) in probands and 44/79(55.6%) in sibs, respectively. Positive bronchial provocation test responses to methacholine were 27/61(44.3%) in sibs, geometric mean of PC20-methacholine were 5.2 mg/ ml in probands and 39.4 mg/ml in sibs, respectively, and slope of dose response curve(mean+- SE, %/mg/ml) were 11.3 +- 3.22 in probands and 1.97 +- 0.5 in sibs, respectively. Of 34 sib-pairs with positive skin test responses to allergens, two D11S97 alleles were shared by 21(61.8% ) sib -pairs, one allele by 11(32.3% ) sib-pairs, and no identical allele by two(5.9% ) sib-pairs. In affected sib-pairs, sharing rate of the alleles was 77.9%, which indicates linkage of the phenotype and genotype(p<0.001). Of 25 sib-pairs with bronchial hyperresponsiveness to methacholine, two D11S97 alleles were shared by seven(28%) sib-pairs, one allele by 11(44%) sib-pairs, and no identical allele by seven(28% ) sib-pairs. In affected sib-pairs, sharing rate of the alleles was 50%, which indicates no linkage between the phenotype and genotype(p) 0.05). Differences of geometric value(mean +- SE) of PC-methacholine and slope of dose response curve(mean +- SE, %/mg/ml) were 1.11+- 0.17 and 8.33+- 3.35 in sib-pairs sharing two alleles, respectively, 0.99 +- 0.14 and 14.27+-5.75 in sib-pairs sharing one allele, respectively, and 0.57+-0.13 and 3.64+-1.62 in sib-pairs sharing no allele, respectively. There was no difference of the above values among the three groups. CONCLUSION: The expression of skin reactivity to common inhalant allergens was linked to gene marker of chromosome 11q13, not with bronchial responsiveness to methacholine.