Maria Cecília F. Almeida

Impaired T Helper 2 Response to Aeroallergen in Helminth-Infected Patients with Asthma

Helminthic infections have been shown to inhibit allergy skin-prick tests and to modify the course of asthma. We evaluated Dermatophagoides pteronyssinus-specific immune responses in patients with asthma by measuring levels of T helper 2 (Th2) cytokines in peripheral blood mononuclear cell (PBMC) cultures. PBMCs from Schistosoma mansoni-infected patients with asthma living in an area of polyhelminthic endemicity produced lower levels of interleukin (IL)-5 and IL-4 in response to D. pteronyssinus antigen (Ag) 1 than did PBMCs from helminth-free patients with asthma. In contrast, D. pteronyssinus Ag 1-specific production of IL-10 was higher in helminth-infected patients than in helminth-free patients. The addition of recombinant human IL-10 to D. pteronyssinus Ag 1-stimulated cultures of PBMCs from helminth-free patients led to down-modulation of production of IL-5. After helminth-infected patients with asthma received antihelminthic treatment, there was down-modulation of D. pteronyssinus Ag 1-specific production of IL-10 in vitro. S. mansoni-infected patients with asthma produce lower levels of Th2 cytokines than do helminth-free patients with asthma, and this modulation is likely done by IL-10.

Low frequency of positive skin tests in asthmatic patients infected with Schistosoma mansoni exposed to high levels of mite allergens.

Helminthic infections and allergic diseases are highly prevalent in many parts of the world. Although skin reactivity to indoor allergens is decreased in subjects from helminthic endemic areas, the degree of exposure to mite allergens has not yet been investigated in these areas. This study evaluated the association between exposure to dust mites and skin reactivity to mite allergens in subjects with a history of wheezing in the last 12 months selected from a rural endemic area for schistosomiasis (group I, n = 21), and two non‐Schistosoma mansoni endemic locale, a rural area (group II, n = 21) and a urban slum area (group III, n = 21). All subjects were evaluated by skin prick tests with mite allergens, and for total and specific immunoglobulin E (IgE) against dust mites, antibodies for S. mansoni, and for intestinal parasites. Dust samples from each subjects’ home were quantified for mite allergen and species of the mite identification. Except for S. mansoni infection which was more prevalent in group I than in groups II and III (p < 0.0001), the prevalence of intestinal parasites, and total and specific IgE levels were similar for all groups. Despite the levels of mite allergens and specifically to Der p 1 detected in dust samples of subjects home from all three areas, the frequency of positive skin reactivity to mite antigens was significantly lower (19.0%) in subjects from group I relative to group II (76.2%) and group III (57.1%; p < 0.001). This result suggests that S. mansoni infection could modulate the immediate hypersensitivity skin response to mite allergens in highly exposed subjects.

Schistosoma mansoni infection alters co-stimulatory molecule expression and cell activation in asthma.

Chronic schistosomiasis induces Th2/T regulatory responses which are able to down-modulate allergic inflammation and asthma. Because co-stimulatory molecules and IL-10 are essential for inducing tolerance, the aim of this study was to determine by flow cytometry, the expression of CD28, CTLA4, CD40L, CD80, CD86, HLA-DR, IL-10 and IL-10 receptor, by mononuclear cells from asthmatic individuals infected with Schistosoma mansoni and compare with non-infected individuals. Peripheral blood mononuclear cells were stained with fluorochrome conjugated antibodies for the expression of co-stimulatory molecules, and for intracellular CTLA4 and IL-10 expression. There was no significant difference in the frequency of T cells expressing CD28 between the two groups. However, the frequency of TCD4(+) cells expressing CTLA4 and CD40L was higher in infected asthmatics. The frequency of monocytes expressing CD80 and CD86 did not differ between groups, while the expression of HLA-DR and IL-10 receptor was higher on monocytes of infected individuals. Furthermore, monocytes and CD4(+)CD25(+) cells of infected individuals expressed higher levels of IL-10. We conclude that, besides alternatively-activated monocytes that are, together with CD4(+)CD25(+) cells, important sources of IL-10, CTLA4 and CD40L expression may also participate in the down-modulation of inflammatory allergic response in S. mansoni-infected asthmatics.

Cytokine and Chemokine Profile in Individuals with Different Degrees of Periportal Fibrosis due to Schistosoma mansoni Infection

Periportal fibrosis in schistosomiasis has been associated to the host immune response to parasite antigens. We evaluated the immune response in S. mansoni infected individuals with different degrees of periportal fibrosis. Cytokine and chemokines were measured in serum and in supernatants of PBMC cultures stimulated with the soluble adult worm (SWAP) or egg (SEA) antigens, using a sandwich ELISA. The levels of IL-5 in response to SEA were higher in individuals with moderate to severe fibrosis (310.9 pg/mL) compared to individuals without fibrosis (36.8 pg/mL; P = 0.0418). There was also a higher production of TNF-α in cultures stimulated with SWAP in patients with insipient fibrosis (1446 pg/mL) compared to those without fibrosis (756.1 pg/mL; P = 0.0319). The serum levels of IL-13 and MIP-1α were higher in subjects without fibrosis than in those with moderate to severe fibrosis. However a positive association between serum levels of IL-13, TNF-α, MIP-1α, and RANTES and S. mansoni parasite burden was found. From these data we conclude that IL-5 and TNF-α may participate in liver pathology in schistosomiasis. The positive association between IL-13, TNF-α, MIP-1α, and RANTES with parasite burden, however, might predict the development of liver pathology.

The Effect of Antihelminthic Treatment on Subjects with Asthma from an Endemic Area of Schistosomiasis: A Randomized, Double-Blinded, and Placebo-Controlled Trial

This is a prospective, double-blinded, and placebo-controlled trial evaluating the influence of antihelminthic treatments on asthma severity in individuals living in an endemic area of schistosomiasis. Patients from group 1 received placebo of Albendazole or of Praziquantel and from group 2 received Albendazole and Praziquantel. Asthma severity was assessed by clinical scores and by pulmonary function test. There was no significant difference in the asthma scores from D0 to D1–D7 after Albendazole or Praziquantel and from D0 to D30–90 after Albendazole or Praziquantel in both, group 1 and 2. It was observed, however, a clinical worsening of the overall studied population after 6 months and 12 months of antihelminthic treatments. Additionally, we observed increased frequency of forced expiratory volume in 1 second (FEV1) <80% on 12 and 18 months after treatment. The worsening of asthma severity after repeated antihelminthic treatments is consistent with the hypothesis of the protective role conferred by helminths in atopic diseases.

Association between mite allergen (Der p 1, Der f 1, Blo t 5) levels and microscopic identification of mites or skin prick test results in asthmatic subjects.

Background: Mite allergens have been involved in airway sensitization and allergic diseases. Immunoassays for the identification and quantifiction of house dust mite (HDM) allergens are useful to improve the knowledge of regional mite fauna and the remediation of mite allergens in allergic diseases. The present study analyzed the association between levels of HDM allergen and results of mite identification or skin prick test (SPT) in two different areas of Bahia, Brazil. Methods: Forty-two asthmatic subjects from a rural area (group I; n = 21) and a slum (group II; n = 21) were evaluated through SPT with HDM allergens and had dust samples collected at their homes for mite identification and allergen measurements. Results: Positive SPT to Dermatophagoides pteronyssinus, Dermatophagoides farinae and Blomia tropicalis allergens were observed in 42.9, 38.0 and 42.9% subjects from group I and in 47.6, 19.0 and 33.3% subjects from group II, respectively. D. pteronyssinus and B. tropicalis were identified in approximately 76 and 50% of samples from both groups, respectively. D. farinae was identified in 38.0 and 9.5% of samples from groups I and II, respectively (p < 0.005). Der p 1, Der f 1 and Blo t 5 detection were associated with mite identification (p < 0.05). Association between HDM allergen levels over 2 µg/g of dust and positive SPT occurred only with D. pteronyssinus (p < 0.0001). Conclusions:D. pteronyssinus was the most prevalent mite species in this study followed by B. tropicalis and D. farinae. Immunoassays done to measure mite allergens were associated with mite-species identification. We conclude that these three mite species must be included on panels for the diagnosis of allergic airway diseases in subjects living in such regions.

Risk Factors for Asthma in a Helminth Endemic Area in Bahia, Brazil

Protective factors associated with atopy or asthma in rural areas include socioeconomic level, overcrowding, and helminth infection. However, little epidemiological information was originated from schistosomiasis areas. This study aimed to investigate factors associated with asthma in a schistosomiasis endemic area. A questionnaire was used to obtain information on demographics, socioeconomic, and environmental features. The ISAAC questionnaire was used to identify individuals with asthma. Parasitological exam was done in all participants and skin prick test to aeroallergens in all asthmatics. Prevalence of Schistosoma mansoni infection was 57.4% and Ascaris lumbricoides, 30.8%. Asthma was found in 13.1% of the population, and 35.1% of them had a positive SPT. Active and passive smoking was positively associated with asthma, whereas A. lumbricoides was negatively associated. In a schistosomiasis hyperendemic region, current infection with A. lumbricoides is protective against asthma. However, we cannot rule out the involvement of S. mansoni infection in this process.

Schistosoma mansoni antigens modulate allergic response in vitro in cells of asthmatic individuals

Schistosoma mansoni infection is associated with a low prevalence of asthma and a less severe form of the disease. The mechanisms underlying this association may include the production of regulatory cells and cytokines. The aim of this study was to evaluate the immune response induced by the S. mansoni antigens, Sm22.6, PIII, and Sm29 and their ability to suppress allergen‐specific IL‐5 production by peripheral blood mononuclear cells (PBMC) from asthmatic individuals. PBMCs were stimulated in vitro with S. mansoni antigens in the presence or absence of antigen‐1 of the mite Dermatophagoides pteronyssinus (Der p1). Cytokines were measured in PBMC supernatants by enzyme‐linked immunosorbent assay (ELISA), and the phenotype of cells producing IL‐10 was assessed using flow cytometry. High production of S. mansoni antigen‐specific IL‐10 was observed not only in cells of S. mansoni‐infected individuals, but also in cells of noninfected asthmatic individuals. In the former group, the main cellular sources of IL‐10 were CD4+ CD25+, and CD14+ cells. The levels of IFN‐γ, IL‐5, and IL‐13 in the noninfected asthmatic group were ∼100 pg/ml in response to the antigens. Moreover, when S. mansoni antigens were added to cultures stimulated with Der p1, levels of IL‐10 were increased (Der p1 = 234 ± 118; Der p1 + Sm22.6 = 1189 ± 595; Derp1 + PIII = 799 ± 331; Derp1 + Sm29 = 652 ± 288 pg/ml) with reduced levels of IL‐5 (Der p1 = 286 ± 219; Der p1 + Sm22.6 = 93 ± 153; Derp1 + PIII = 132 ± 188; Derp1 + Sm29 = 96 ± 86 pg/ml). The S. mansoni antigens evaluated in the present study induced the production of the regulatory cytokine IL‐10 and down‐modulated the Th2 immune response that participates in the pathology of asthma. Drug Dev Res 72:538–548, 2011.

Citologia do escarro induzido em asmáticos infectados pelo Schistosoma mansoni

A infeccao pelo Schistosoma mansoni inibe manifestacao da asma. A avaliacao do escarro induzido em pacientes infectados pelo parasita pode trazer informacoes importantes sobre a relacao entre doencas alergicas e parasitoses. Objetivo: Avaliar a celularidade do escarro em asmaticos em uma area endemica em esquistossomose na Bahia. Metodos: Estudo randomizado, duplo cego, controlado com placebo, incluindo asmaticos infectados pelo S. mansoni e um grupo de asmaticos nao infectados. Foi utilizada a celularidade do escarro induzido, em contagens sequenciais pre (D0) e pos-tratamento (D7, D60 e D90), para avaliar os efeitos do tratamento da parasitose com praziquantel sobre a asma. Resultados: Avaliados 22 individuos asmaticos infectados pelo S. mansoni e grupo controle adicional composto por oito asmaticos nao infectados. O grupo que usou praziquantel nao diferiu do grupo placebo quando comparada a celularidade do escarro. Houve aumento no numero de eosinofilos nos D7, D60 e D90 no grupo placebo, quando comparados ao basal, e no D60 no grupo praziquantel. O numero total de celulas aumentou em relacao ao basal no D7 e no D90 para o grupo placebo, e no D90 para o grupo praziquantel. O grupo que usou praziquantel apresentou uma reducao do volume expiratorio forcado no 1o segundo (VEF1) no D7, D60 e D90. Nao houve associacao entre a eosinofilia e a gravidade da asma. Conclusao: No presente estudo nao foi encontrada correlacao entre os tipos celulares encontrados e a gravidade da asma, nem houve variacao significativa do percentualde eosinofilos em resposta ao tratamento da esquistossomose...(AU) Schistosoma mansoni infection inhibits asthma symptoms. Assessment of induced sputum in infected patients may shed light on the relationship between allergic diseases and parasite infections. Objective: To assess the cellularity of induced sputum in asthmatic patients living in an endemic area of schistosomiasis in the Brazilian state Bahia. Methods: This randomized, double blind, placebo-controlled study included asthmatic patients infected with S. mansoni and a group of non-infected asthmatics (controls). Cellularity of induced sputum was analyzed based on cell counts before (D0) and after treatment (D7, D60, and D90), to evaluate the effects of treatment with praziquantel on asthma. Results: A total of 22 asthmatics infected with S. mansoni and 8 controls were assessed. Induced sputum cellularity in the group treated with praziquantel did not differ from that of the group treated with placebo. However, compared to baseline counts, a higher number of eosinophils was found in the placebo group on D7, D60, and D90, and on D60 in the treatment group. Total cell counts increased from baseline to D7 and D90 in the placebo group, and from baseline to D90 in the treatment group. Moreover, the treatment group showed a reduction in forced expiratory volume in 1 second (FEV1) on D7, D60, and D90. There was no association between eosinophilia and asthma severity. Conclusion: In the present study, there was no correlation between asthma severity and the cell types found during cellularity assessment, nor was there an association between treatment of schistosomiasis and sputum eosinophilia...(AU)