Different frequencies of Tc17/Tc1 and Th17/Th1 cells in chronic spontaneous urticaria.

BACKGROUND: Chronic urticaria is associated with an immune dysregulation usually mediated by T lymphocytes. Recently, Th17 and Tc17 have been implicated in autoimmune diseases; however, their role in urticaria is not clear yet. METHODS: For the study we recruited 20 patients [10 of them had autoreactive chronic spontaneous urticaria (positive autologous intradermal serum test response, ASST+), and the other 10 were nonautoreactive chronic spontaneous urticaria patients (ASST-)] and 17 healthy age- and gender-matched controls (HG). The frequency and functional activity of Th17/Tc17 and Th1/Tc1 cells were evaluated by flow cytometry and type 2 cytokine mRNA by real-time PCR. RESULTS: Our results demonstrated a significant decrease in Th17 frequency in both chronic urticaria groups compared to HG; regarding the amount of IL-17, at the single cell level, it was reduced in ASST- compared to HG. Concerning the Th1 and Th17 cells producing IFN-γ, IL-2, and TNF-α, a lower frequency was noted in chronic urticaria patients compared to HG. In contrast, a significantly increased frequency of Tc1 cells producing these cytokines was noted in ASST+ compared to HG and ASST-. Also, the frequency of Tc17 cells producing TNF-α was increased in ASST+ compared to HG; however, with respect to the amount of TNF-α, at the single cell level, we found a decrease in ASST+ compared to HG. Regarding type 2 cytokine mRNA, a higher expression was verified in ASST+ compared to HG. CONCLUSION: Our data suggest a probable involvement of cytotoxic T cells, mainly the Tc1 and Tc17 subsets, in chronic urticaria, particularly in the ASST+ group.

Effect of Dermatophagoides specific immunotherapy on cutaneous reactivity.

BACKGROUND: There are several immunological and clinical effects induced by specific immunotherapy (SIT). A reduction of reactivity to allergen is the final propose of this therapy. The aim of this study was to evaluate the specific cutaneous reactivity, two years after beginning SIT. METHODS: We included 95 patients with bronchial asthma (BA) and/or allergic rhinitis (AR) to house dust mites (HDM). 74 patients were submitted to subcutaneous SIT with commercial extracts of Dermatophagoides. The control group included the 21 patients without SIT. After a two years period, the cutaneous reactivity was reassessed, by skin prick tests (SPT). The effect of SIT in the cutaneous response was evaluated by calculating the difference between the wheal diameter of the SPT before and after treatment. A positive difference indicated a cutaneous reactivity reduction. RESULTS: The patients submitted to SIT included 52.7% males and 47.3% females, with a mean age of 18.4 +/- 13.9 years old. The cutaneous reactivity to D. pteronyssinus, before and two years after the beginning of SIT, were 6.9 +/- 3 mm and 5.1 +/- 2.9 mm, respectively, with 1.87 of difference (p = 0.0001). The cutaneous reactivity to D. farinae, before and two years after the beginning of SIT, were 6.2 +/- 2.4 mm and 5.0 +/- 3.7 mm, respectively, with 0.93 of difference (p = 0.0790). In the control group, the cutaneous reactivity to D. pteronyssinus was 4.4 +/- 2.1 mm and two years later it was 8.2 +/- 3.7 mm. The difference was -1.53 (p = 0.1590). The cutaneous reactivity to D. farinae was 4.6 +/- 2.2 mm in the first evaluation and 8.3 +/- 4.7 mm two years later. The difference was -2.63 (p = 0.0470). CONCLUSIONS: This study showed a significant reduction of specific cutaneous reactivity induced by Dermatophagoides SIT. In the control group the cutaneous reactivity to Dermatophagoides revealed an increment.

Increased prevalence of allergic sensitisation in rheumatoid arthritis patients treated with anti-TNFalpha.

INTRODUCTION: Tumour necrosis factor alpha (TNFalpha) has emerged as a therapeutic target in chronic inflammatory disorders characterised by a Th1 type immune response, such as rheumatoid arthritis (RA). The presence of allergic disease in these patients could be influenced both by the presence of RA and anti-TNFalpha therapy. Our aim was to evaluate the prevalence of sensitisation to airborne allergens and allergic disease in RA patients, with and without anti-TNFalpha treatment. METHODS: RA patients with (N=20) and without (N=20) anti-TNFalpha therapy (groups T and R) were enrolled. Healthy controls (N=60, group C) were randomly selected from the general population. All participants answered a standardised questionnaire to assess the prevalence of allergic disease and had skin prick tests (SPT) with a standard panel of airborne allergen extracts. RESULTS: Significant differences were found in the prevalence of positive SPT between groups T and R (70% vs 35%, p=0.027) and groups T and C (70% vs 36.7%, p=0.009), but not between groups R and C. The prevalence of allergic disease was similar in the three groups. Groups T and R had similar gender and age distribution, disease duration, disease activity score (DAS28), erythrocyte sedimentation rate and serum C-reactive protein. CONCLUSIONS: Increased prevalence of sensitisation to airborne allergens in RA patients treated with anti-TNFalpha was found. The clinical impact of the positive SPT following anti-TNFalpha initiation has now to be assessed.

Specific sublingual immunotherapy with peach LTP (Pru p 3). One year treatment: a case report.

INTRODUCTION: Food allergy is an increasing problem with limited therapeutic approaches apart from to the eviction diet. CASE PRESENTATION: A 40-year-old female patient with food allergy symptoms was polysensitized to almost all vegetable food since the age of 36; the onset of symptoms was during pregnancy. The allergological study demonstrated positive skin prick tests (SPT) to nuts, legumes, cereals, spices, several fresh fruits including peach, and other groups of vegetable foods however, it was negative to common aeroallergens. Serum specific IgE levels were negative (<0.35 kU/L) to profilin and carbohydrate determinants, but positive to Pru p 3 (3.5 kU/L). Positive double-blind placebo-controlled food challenge to peach confirmed the allergic disease. She received specific sublingual immunotherapy with native Pru p 3 at a concentration of 40 mug/ml with 5 administrations per week and a cumulative dose of 200 mug of nPru p 3 per month. After an ultra-rush build-up phase concluded in one day she continued therapy during a year with 5 administrations per week. The clinical evolution and laboratory studies demonstrated an early reduction on SPT reactions with no relevant changes on serum specific IgE, IgG, IgG(1) and IgG(4) to Pru p 3 during the immunotherapy period. The challenge test was negative 4 months after the beginning of the SLIT. Regarding clinical response she markedly improved after the first month of treatment, and by the 3th month she had no major vegetable dietary restrictions, except for nuts and pepper. CONCLUSION: These results demonstrate the excellent efficacy and safety of sublingual specific protein immunotherapy developed according to the patient specific sensitivity profile to Pru p3.

Arthritis and X-linked agammaglobulinemia.

Primary immunodeficiencies are defined as genetically determined functional and/or quantitative abnormalities in one or more of the components of the immune system. Immunodeficiency and arthritis can be related, although the mechanisms are not always clear. Different causes for immunodeficiency can secondarily be found in patients with arthritis; on the other hand, arthritis can be a manifestation of primary immunodeficiency. Arthritis occurs chiefly in humoral primary immunodeficiencies, namely in X-linked agammaglobulinemia and common variable immunodeficiency, and may be one of the warning signs for primary immunodeficiency. We report a case of arthritis as the presenting feature of X-linked agammaglobulinemia. In X-linked agammaglobulinemia, arthritis may be a consequence of infection, most notably by Mycoplasma, or of immune dysfunction itself. In children, and occasionally in young adults, a combination of arthritis and hypogammaglobulinemia should suggest primary immunodeficiency, although other causes of hypogammaglobulinemia must be excluded. Physicians evaluating patients with arthritis should be aware of this fact so that an early diagnosis can be pursued as it is of extreme importance in the optimal management and prognosis of these patients.

Home gardening may be a risk factor for contact dermatitis to Alstroemeria.

BACKGROUND: Occupational allergy among florists and people who work in cut flower production of Alstroemeria cultivars (Peruvian lily or Inca lily) has been previously reported. The allergen involved in sensitization is tulipalin A (alpha-methylene-gamma-butyrolactone). CASE REPORT: We describe the case of a 65-year-old woman who developed severe dermatitis on her right thumb, index and middle fingers and less severe dermatitis on her left palm and front of forearm with occasional itching of the neck and face after taking up home gardening activities, including cutting flowers such as Alstroemeria. METHODS: The patient and three healthy individuals were submitted to epicutaneous tests with the European standard series, the plant series, and stem portions of three suspected ornamental plants (Alstroemeria, Lilium and Zantedeschia), garlic, and onion. RESULTS: Patch tests performed in our patient, revealed an extreme reaction (+ + +) to Alstroemeria and alpha-methylene-gamma-butyrolactone, a strong reaction (+ +) to propolis and wood tar mix, a weak reaction (+) to balsam of Peru, an irritant reaction to garlic and negative results to diallyl disulfide and the other components investigated. Patch tests performed in the healthy individuals revealed negative. CONCLUSIONS: We stress the importance of Alstroemeria as a cause of allergic contact dermatitis not only in workers involved in the flower trade, but also in other people that come into contact with this plant in their leisure activities.

Home gardening may be a risk factor for contact dermatitis to Alstroemeria / La jardinería puede ser un factor de riesgo de dermatitis de contacto por alstroemeria

Background: Occupational allergy among florists and people who work in cut flower production of Alstroemeria cultivars (Peruvian lily or Inca lily) has been previously reported. The allergen involved in sensitization is tulipalin A (alpha-methylene-gamma-butyrolactone). Case report: We describe the case of a 65-year-old woman who developed severe dermatitis on her right thumb, index and middle fingers and less severe dermatitis on her left palm and front of forearm with occasional itching of the neck and face after taking up home gardening activities, including cutting flowers such as Alstroemeria. Methods: The patient and three healthy individuals were submitted to epicutaneous tests with the European standard series, the plant series, and stem portions of three suspected ornamental plants (Alstroemeria, Lilium and Zantedeschia), garlic, and onion. Results: Patch tests performed in our patient, revealed an extreme reaction (+ + +) to Alstroemeria and alpha-methylene-gamma-butyrolactone, a strong reaction (+ +) to propolis and wood tar mix, a weak reaction (+) to balsam of Peru, an irritant reaction to garlic and negative results to diallyl disulfide and the other components investigated. Patch tests performed in the healthy individuals revealed negative. Conclusions: We stress the importance of Alstroemeria as a cause of allergic contact dermatitis not only in workers involved in the flower trade, but also in other people that come into contact with this plant in their leisure activities

Antecedentes: La alergia ocupacional entre las floristas y en los trabajadores de producción de flores de corte de cultivos de Alstroemeria (lirio Peruano o lirio Inca) fue ya objeto de descripción. La Tulipalina A (alfa-metileno-gama-butirolactona) es lo alergeno involucrado en la sensibilización. Caso clínico: se presenta un caso de una paciente de 65 años que ha iniciado una dermatitis grave en los 1º, 2º y 3º dedos de la mano derecha, bien como una dermatitis de intensidad moderada en la área palmar izquierda y vista anterior de lo antebrazo homolateral. Ocasionalmente, los síntomas se acompañan de prurito de la cara y cuello, en el decurso de actividades de jardinaje en su casa, incluyendo el corte de flores de Alstroemeria. Métodos: Fueron realizadas pruebas epicutáneas con la serie estándar europea, la serie de plantas, y porciones de tallo de tres plantas sospechas (Alstroemeria, Lilium y Zantedeschia), ajo y cebolla. Resultados: Las pruebas revelaron una reacción severa (+++) a Alstroemeria y alfa-metileno-gama-butirolactona, una reacción intensa (++) a propolis y mixtura de alquitranes de la madera, una reacción ligera (+) a bálsamo Perú, una reacción irritativa a ajo y resultados negativos a dialil disulfido, bien como a todos los demás estudiados. Conclusiones: Este caso clínico reporta la importancia de la Alstroemeria como inductor de dermatitis de contacto alérgica, non solo en trabajadores de floricultura, pero también en individuos comunes que puedan contactar con esta planta en sus actividades de tiempos libres

Síndrome ave-ovo. Haverá novos alérgenos envolvidos? / Bird-egg syndrome. Are there new allergens involved?

Objetivo: Identificar alérgenos, além da -livetina, que possam ser responsáveis por reatividade cruzada em pacientes com síndrome ave-ovo. Métodos: Estudamos três pacientes do sexo feminino (63, 66 e 42 anos), com anafilaxia após ingestão de ovo, asma brônquica e rinoconjuntivite quando expostas a aves. A sensibilização a antígenos de ovo, gema, clara, ovomucóide, ovalbumina,carne de galinha e penas foi investigada por: testes cutâneos por puntura (TC) e determinação dos níveis de IgE sérica específica (sIgE). Foram efetuados immunoblots IgE para ovo, clara, gema, carne e penas de galinha e inibidos, à exceção do blot de carne, com extrato de gema, clara e penas de galinha. Resultados: Todos os pacientes manifestaram TC positivos para os antígenos testados, exceto o caso 1 que recusou ser testada ao ovo e seus componentes e à carne. Em todos, foi detectada sIgE 4 0,81 KU/l, exceto no caso 3, que não evidenciou sIgE para gema e carne, e no caso 2 em que a sIgE para carne não foi detectável. A análise comparativa do immunoblot de penas com os de ovo, gema, clara e carne, revelou ligação da IgE a várias proteínas com peso molecular semelhante, nomeadamente de 31, 35-37, 53 e 67-70 kDa. Os immunoblots de penas foram quase completamente inibidos após pré-incubação do soro com extratos de gema e clara. Os immunoblots de gema, clara e ovo foram inibidos após pré-incubação do soro com extrato de penas, embora em menor extensão. Conclusão: Além da alfa-livetina, existem outros alérgenos responsáveis por reatividade cruzada que poderão estar implicados na síndrome ave-ovo.

Imunoterapia específica - avaliação dinâmica e cinética in vivo do extrato terapêutico em doentes alérgicos / Specific immunotherapy - in vivo dinamic and kinetic evaluation of a therapeutic extract in allergic patients

Introdução: A imunoterapia específica (IT) é uma forma comum de tratamento da doença alérgica. O mecanismo preciso desta terapêutica não é conhecido, embora a eficácia clínica esteja plenamente documentada. O objetivo deste estudo foi avaliar a cinética da IT , aplicando uma técnica de Medicina Nuclear, marcação de leucócitos com 99mTc-HMPAO, em doentes em fase de manutenção e com excelente eficácia clínica à terapêutica.Pacientes e métodos: Foram estudados 14 doentes alérgicos agrupados de acordo com o tipo de extrato e via de administração: extratos aquosos subcutâneos (látex= 4 doentes; veneno de abelha= 2 doentes), extrato depot subcutâneo (ácaros= 2 doentes; gramíneas= 2 doentes); extrato modificado subcutâneo (gramíneas= 1 doente; Parietária= 1 doente) extrato sublingual (ácaros= 2 doentes). O grupo controle foi constituído por dois doentes alérgicos a ácaros, submetidos respectivamente a: injecção subcutânea de soluto salino e injecção de extrato bacteriano por via subcutânea (controle positivo).Simultaneamente à administração do extrato alergênico terapêutico, procedeu-se à re-injecção de leucócitos marcados com 99mTc-HMPAO, em veia periférica contralateral. A aquisição dinâmica decorreu durante 60 minutos, com matriz de 64x64, 2 imagens/ minuto em projeção torácica anterior. As aquisições estáticas, com matrizes 256x256, durante 5 minutos cada foram adquiridas aos 60, 90, 120, 180, 240, 300 e 360 minutos, em projeção torácica (anterior e posterior) e abdominal (anterior).Resultados: A atividade inflamatória no ocal de administração da IT para os extratos subcutâneos aquosos e depot iniciou-se na primeira hora e manteve um aumento ao longo do tempo de estudo. Para os extratos sublinguais a atividade inflamatória foi observada logo nos primeiros minutos. Todos os estratos subcutâneos condicionaram dreanagem linfática ascendente para áreas axilares homolaterais nos primeiros minutos após a adminstração do extrato e, posteriormente, para tecido linfóide do mediastino superior e anterior, e áreas cervicais. As focalizações torácicas estiveram presentes em todos os doentes estudados, o mesmo não acontecendo para a atividade de intestinal. A via sublingual não induziu focalizações axilares ou instetinais, mesmo tendo havido deglutição do alérgeno. Foram calculados coeficientes corrigidos de captação em áreas individualizadas (ROIs- region of interest) em relação aos coeficientes de captação das áreas de background.