Joanemile P. Figueiredo

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.

Adult worm-specific IgE⁄IgG4 balance is associated with low infection levels of Schistosoma mansoni in an endemic area

Field studies have suggested an immune‐mediated mechanism associated with resistance to Schistosoma mansoni infection. Overall, levels of specific IgE have been correlated with resistance to infection, whereas levels of IgG4 have been associated with susceptibility. This study aimed to evaluate serum levels of soluble adult worm antigen preparation (SWAP)‐specific IgE and IgG4 in relation to current infection in a large casuistic of individuals living in an endemic area of schistosomiasis in Bahia, Brazil. The prevalence of S. mansoni infection was 37·7% and the mean parasite burden was 55·4 (0–2100) epg/faeces. There was no significant difference in the levels of SWAP‐specific IgE in individuals with different parasite burden, whereas high producers of parasite‐specific IgG4 presented higher parasite burden when compared to low IgG4 producers. Additionally, S. mansoni parasite load was positively correlated with the levels of specific IgG4 or total IgE. No significant correlation was observed between parasite burden and SWAP‐specific IgE. Nevertheless, SWAP‐specific IgE/IgG4 ratio was higher in uninfected or lightly infected individuals (1–99 epg/faeces) than in heavily infected ones (≥400 epg/feces). These findings highlight the important role of IgE/IgG4 ratio in the resistance to infection, which could be useful for further studies in schistosomiasis vaccine candidates.

Factors Associated with Resistance to Schistosoma mansoni Infection in an Endemic Area of Bahia, Brazil

Detailed knowledge of factors associated with resistance to Schistosoma mansoni infection in endemic areas might facilitate more effective schistosomiasis control. We conducted a cross-sectional study of persons resistant to schistosomiasis and found no association between socioeconomic status and resistance to infection. Mononuclear cells of resistant subjects produced higher levels of interleukin-5 (IL-5), IL-13 and interferon-γ upon stimulation with soluble egg antigen (SEA) compared with infected persons. When stimulated with Sm21.6 or Sm22.6, levels of IL-10 were higher in cell culture of resistant persons. Levels of IgE against soluble adult worm antigen (SWAP) and against interleukin-4-inducing principle from S. mansoni eggs (IPSE) and levels of IgG4 against SWAP, SEA, and Sm22.6 were lower in the resistant group compared with the susceptible group. Our data suggest that socioeconomic status could not fully explain resistance to S. mansoni infection observed in the studied area. However, a mixture of Th1 and Th2 immune responses and low levels of specific IgG4 against parasite antigens could be mediating resistance to infection.

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.