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Biomedical subjects

M I Araújo

Publications and source records attributed to M I Araújo.

7 recordsLinked to original sources

Worms and allergy.

Worms and asthma are associated with a type 2 immune response, but evidence has accumulated that helminth infection is negatively associated with atopy, prevalence of allergic diseases and severity of asthma. One important difference between these polarized type 2 responses is that in allergy modulation of the immunological response is not appropriate, whereas in infection with helminths, several host mechanisms down-regulate the host immune response. As a result, patients infected with worms have a decrease in both type 1 and type 2 responses. The main mechanism involved in this down-modulation is increased production of IL-10, but expansion of regulatory T cells and NKT cells may also participate. Regarding the interaction between worms and allergy, a few variables need to be taken in account: phase (acute or chronic) of helminth infection, parasite load and species of helminth. In animals and humans, acute helminth infection may increase manifestations of allergy, whereas chronic infection with parasites decreases atopy. The modulation of the immune response by helminths is dependent on having an adequate parasite load. Moreover, although several helminth species have been shown to modulate immune responses, most in vitro and in vivo studies have focused on the importance of Schistosoma mansoni in down-modulating allergic reactions.

Animals↗

IgG anti-IgE autoantibodies in visceral leishmaniasis.

Procedures for IgG depletion in visceral leishmaniasis (VL) and schistosomiasis sera using Sepharose-protein G beads also deplete IgE. In this study, the presence of IgG anti-IgE autoantibodies in sera from patients with VL (n = 10), and hepatic-intestinal schistosomiasis (n = 10) and from healthy individuals (n = 10) was investigated. A sandwich ELISA using goat IgG anti-human IgE to capture serum IgE and goat anti-human IgG peroxidase conjugate to demonstrate the binding of IgG to the IgE captured was performed. VL sera had higher titers (p < 0.05) of IgG anti-IgE autoantibodies (OD = 2.01 +/- 0.43) than sera from healthy individuals (OD = 1.35 +/- 0.16) or persons infected with Schistosoma mansoni (OD = 1.34 +/- 0.18). The immunoblotting carried out with eluates from Sepharose-protein G beads used to deplete IgG from these sera and goat anti-human IgE peroxidase conjugate, showed a similar pattern of bands, predominating the 75 kDa epsilon-heavy chain and also polypeptides resulting from physiological enzymatic digestion of IgE. A frequent additional band immediately above 75 kDa was observed only in VL sera.

Antibodies, Anti-Idiotypic↗

Detection of specific IgE antibodies in parasite diseases.

Activation of Th1 or Th2 cells is associated with production of specific immunoglobulin isotypes, offering the opportunity to use antibody measurement for evaluation of T cell function. Schistosomiasis and visceral leishmaniasis are diseases associated with Th2 activation. However, an IgE response is not always detected in these patients. In the present study we evaluated specific IgE antibodies to S. mansoni and L. chagasi antigens by ELISA after depletion of serum IgG with protein G immobilized on Sepharose beads or RF-absorbent (purified sheep IgG antibodies anti-human IgG). In schistosomiasis patients, specific IgE to SWAP antigen was demonstrable in only 10 of 21 patients (48%) (mean absorbance +/- SD = 0.102 +/- 0.195) when unabsorbed serum was used. Depletion of IgG with protein G increased the number of specific IgE-positive tests to 13 (62%) and the use of RF-absorbent increased the number of positive results to 20 (95%) (mean absorbances +/- SD = 0.303 +/- 0. 455 and 0.374 +/- 0.477, respectively). Specific IgE anti-L. chagasi antibodies were not detected in unabsorbed serum from visceral leishmaniasis patients. When IgG was depleted with protein G, IgE antibodies were detected in only 3 (11%) of 27 patients, and the use of RF-absorbent permitted the detection of this isotype in all 27 visceral leishmaniasis sera tested (mean absorbance +/- SD = 0.104 +/- 0.03). These data show that the presence of IgG antibodies may prevent the detection of a specific IgE response in these parasite diseases. RF-absorbent, a reagent that blocks IgG-binding sites and also removes rheumatoid factor, was more efficient than protein G for the demonstration of specific IgE antibodies.

Animals↗

Evidence of a T helper type 2 activation in human schistosomiasis.

The lymphocyte proliferative response and cytokine production to S. mansoni antigen in vitro were evaluated in 22 schistosomiasis patients living in an area endemic for this disease. The majority of patients (86%) showed no lymphocyte proliferative response and none of them showed interferon-gamma (IFN-gamma) production, following in vitro stimulation with soluble adult worm antigen preparation (SWAP). In contrast, interleukin (IL)-5 (2038 +/- 1757 pg/ml) and IL-10 (867 +/- 762 pg/ml) were detected in peripheral blood mononuclear cell (PBMC) cultures stimulated with SWAP. Moreover, mRNA for IL-4 was detected in SWAP-stimulated PBMC from 4 of 6 patients evaluated. Restoration of lymphoproliferative response was achieved in 4 of 6 patients by adding anti-IL-10 monoclonal antibody (mAb) to PBMC cultures [mean stimulation index (SI) in the presence of antigen = 2.7 +/- 2.9; SI in the presence of antigen plus anti-IL-10, 21 +/- 16]. Restoration of IFN-gamma production by addition of anti-IL-10 mAb was achieved in 4 of 12 patients evaluated (248, 350, 687 and 710 pg/ml). Moreover, the addition of IL-10 to PBMC cultures of 3 schistosomiasis patients and 2 cured subjects who had high lymphoproliferative responses to SWAP resulted in the suppression of these responses by 90%, and completely suppressed IFN-gamma production in one of the subjects, whose PBMC produced IFN-gamma after stimulation with SWAP. The presence of IL-4 mRNA, high levels of IL-5, and the absence of IFN-gamma in PBMC culture supernatants from infected patients, supports the conclusion that patients living in an endemic area of schistosomiasis express a predominant T helper type 2 response. The high levels of IL-10 and the ability of neutralizing anti-IL-10 mAb to restore T cell responses indicate that this cytokine plays an important role in the modulation of T cell responses in schistosomiasis.

Adolescent↗

The absence of gamma-interferon production of S. mansoni antigens in patients with schistosomiasis.

No gamma-interferon production was observed in peripheral blood mononuclear cells (PBMC) cultures from 45 patients living in an endemic area of schistosomiasis in Brazil following in vitro stimulation with schistosomula or adult worm antigens from Schistosoma mansoni (4.9 +/- 24 and 1.0 +/- 3.4 pg/ml, respectively). This immunological abnormality was observed in patients both with a high degree of infection (> or = 400 eggs/g feces) and with a low degree of infection (< 400 eggs/g feces), and was independent of the degree of natural exposure to infection. This absence of gamma-interferon production was antigen specific since high levels of this cytokine were detected in the same patients when their cells were stimulated with PPD (247 +/- 179 pg/ml) or PHA (408 +/- 328 pg/ml). In two of four subjects cured of a previous S. mansoni infection and currently living outside the endemic area, gamma-IFN was produced when their PBMC were stimulated with adult worm antigen (75 +/- 2.5 pg/ml).

Adolescent↗

[Evaluation of the sensitization power of Montenegro skin test].

The Montenegro skin test, used to diagnose cutaneous leishmaniasis, is now being considered to detect immunogenicity after vaccination. In this study, we evaluated the ability of this test to induce immune response and IFN-g production in subjects not previously exposed to Leishmania. The Montenegro skin test was performed using antigens of L. amazonensis produced by our laboratory (group I) or by FIOCRU-RJ (group II). At day 30, 33% of the subjects from group I and 42% from group II were positive, compared to 67% from group I and 50% from group II at day 90. IFN-y was detected in 56 % of subjects from group I and 17% from group II at day 30 (169+/-309 and 11+/-36pg/ml) and in 67% from group I and 58% from group II by day 360 (69+/-107 and 18+/-20pg/ml). These data demonstrate that the Montenegro skin test induces not only a delayed hypersensitivity reaction, but also IFN-y production.

Adolescent↗

[Primary disorders of neutrophils: principal clinical and laboratory aspects].

This article presents a review of different categories of inherited neutrophil dysfunctions, such as chronic granulomatous disease, disorders of chemotaxis, defects of degranulation and the leukocyte adherence deficiency. The clinical manifestations and laboratory findings of these phagocyte abnormalities, with particular reference to various tests of neutrophil functions used for diagnostic elucidation are described.

Cell Degranulation↗