Changes in IgE- and Antigen-dependent histamine-release in peripheral blood of Schistosoma mansoni-infected Ugandan fishermen after treatment with praziquantel
© Satti et al; licensee BioMed Central Ltd. 2004
Received: 21 January 2004
Accepted: 21 April 2004
Published: 21 April 2004
Parasite-specific IgE levels correlate with human resistance to reinfection with Schistosoma spp. after chemotherapy. Although the role of eosinophils in schistosomiasis has been the focus of a great deal of important research, the involvement of other Fcε receptor-bearing cells, such as mast cells and basophils, has not been investigated in relation to human immunity to schistosomes. Chemotherapy with praziquantel (PZQ) kills schistosomes living in an in vivo blood environment rich in IgE, eosinophils and basophils. This releases parasite Ags that have the potential to cross-link cell-bound IgE. However, systemic hypersensitivity reactions are not induced by treatment. Here, we describe the effects of schistosomiasis, and its treatment, on human basophil function by following changes in total cellular histamine and in vitro histamine-release induced by schistosome Ags or anti-IgE, in blood samples from infected Ugandan fishermen, who are continuously exposed to S. mansoni infection, before and 1-day and 21-days after PZQ treatment.
There was a significant increase in the total cellular histamine in blood samples at 1-day post-treatment, followed by a very significant further increase by 21-days post-treatment. In vitro histamine-release induced by S. mansoni egg (SEA) or worm (SWA) Ags or anti-IgE antibody, was significantly reduced 1-day post-treatment. The degree of this reduction correlated with pre-treatment infection intensity. Twenty-1-days post-treatment, SEA-induced histamine-release was still significantly lower than at pretreatment. Histamine-release was not correlated to plasma concentrations of total or parasite-specific IgE, nor to specific IgG4 plasma concentrations.
The biology of human blood basophils is modulated by S. mansoni infection and praziquantel treatment. Infection intensity-dependent suppression of basophil histamine-release, histamine-dependent resistance to infection, and similarities with allergen desensitisation are discussed as possible explanations of these observations.
High levels of circulating IgE are characteristic of both parasitic helminth infections and hypersensitivity conditions such as asthma and allergy. IgE and other Th2 mediated responses have been shown to be important in immunity to helminth infections. In human populations living in schistosomiasis endemic areas, high levels of IL-4, IL-5 [1, 2], eosinophilia  and parasite-specific IgE are associated with resistance to reinfection after chemotherapy [4–6]. In previous studies in Kenya, levels of IgE specific for the adult Schistosoma mansoni worm, when measured after PZQ treatment but before re-infection, negatively correlated with subsequent reinfection intensities . Specific IgE responses against Ags present in the outer tegument of the adult worm were also significantly associated with resistance to reinfection after treatment . Human IgE and eosinophils have been shown to combine in antibody-dependent, cellular cytotoxicity mechanisms (ADCC) to kill early schistosome larvae in vitro. However, this mechanism may not be as effective in vivo as, on penetration of its vertebrate host, the parasite rapidly disguises its outer tegumental surface by absorbing host Ag  and also becomes innately refractory to ADCC killing . The roles of other major Fcε receptor-bearing effector cells such as mast cells and basophils has yet to be defined in human immunity to schistosomiasis. In vitro basophil studies have suggested a secretagogue potential of some S. mansoni Ag [12, 13] or of plasma factors from infected patients , but the relationship between S. mansoni infection and basophils, and its relationship with human susceptibility to infection/reinfection, is not known. The role of basophils in allergy is an active area of research. Interestingly, it is suggested that allergic diseases are less prevalent in areas that are endemic for helminth infections and, when they are present, the manifestations of these diseases are less severe in helminth-infected individuals . Various immune regulatory processes have been put forward as candidate mechanisms for the control of the potentially adverse effects of IgE responses in connection to both potential hypersensitivity to helminth Ags themselves and allergy in general .
Chemotherapy to kill schistosome worms whilst they are living in an intravenous environment that is rich in IgE, eosinophils and basophils, would seem to have the potential to induce a systemic hypersensitivity reaction. Orally administered PZQ, the drug of choice, is rapidly absorbed into the blood, where it can be metabolised within 90 minute. Within one hour of contact with PZQ, the outer tegument of the worm is severely disrupted . This rapid disruption of the worm tegument would lead to the exposure of worm Ags, some known to be recognised by IgE , directly to the blood. Despite this, only a very few heavily infected older individuals have transient hypersensitivity responses, usually within a few hours of treatment, such as urticaria and oedema. This suggests that some aspect(s) of infection or reactions between infection and host response to infection, circumvents the most potentially damaging effects of systemic interactions between specific-IgE, mass-released parasite Ags and immune effector cells such as mast cells, eosinophils and basophils.
Here we describe the effects of schistosomiasis and the intravenous killing of the parasite on basophil function by following the changes in total cellular histamine content and in vitro basophil histamine-release induced by schistosome Ags or anti-IgE Ab. The studies were carried out using washed blood from infected Ugandan fishermen, before and at 1-day and 21-days after they were treated with PZQ.
Results and discussion
Increases in total cellular histamine content of blood in S. mansoni infected individuals 1-day and 21-days after treatment
Total cellular histamine content in the blood of S. mansoni-infected individuals, pre- and post-treatment, and in non infected individuals.
Median total cellular histamine content (ng/ml)
pre-treatment (N = 32)
81.0 (43.5 – 97.0)
1 day post treatment (N = 29)
108.0 (85.5 – 145.5)
21 days post-treatment (N = 25)
160.5 (83.8 – 278.8)
non-infected (N = 8)
179.0 (163.0 – 248.5)
Changes in maximal histamine-release from the blood of S. mansoni-infected individuals 1-day after treatment
Histamine released from the blood of S. mansoni-infected individuals, pre- and post-treatment, after in vitro stimulation with anti-IgE or schistosome Ag.
pre-treatment (N = 32)
1-day post-treatment (N = 29)
16.5 (9.8, 26.0)
21-days post-treatment (N = 25)
At 1-day post-treatment, most individuals showed decreased histamine-releasability (Figure 2). Histamine-releasability induced by SEA (p = 0.002, n = 21); SWA (p = 0.004, n = 23); and anti-IgE (p = 0.001, n = 23) dropped very significantly, as did the absolute amount of released histamine (Table 2). This reduced ability to release cellular histamine, including after anti-IgE stimulation, suggests a general desensitisation, similar to that reported in the desensitization of individuals to specific allergens by either sub-optimal or super-optimal IgE receptor activation [24–26]. Praziquantel is a short acting drug that quickly causes the release of Ags from damaged worms and eggs. This may result in a rapid, in vivo basophil degranulation that desensitises the basophils to further Ag stimulation. Since total cellular histamine is low, the extent of such an early release would be limited, as shown in Table 2 by the absolute amount of released histamine lower at pre-treatment than at 21 days post-treatment, thus preventing the onset of hypersensitivity reactions after treatment. Additionally, any such early in vivo release of histamine may down-regulate further release through an autocrine mechanism involving H2 receptors .
A alternative explanation of this down-regulated histamine-releasability, in the presence of increased cellular histamine content, may be that after the worms and eggs destruction and subsequent release of parasite Ags by Praziquantel treatment, immature bone marrow basophils were freshly released into the blood. This mechanism has been suggested as the cause of increased basophil counts associated with reduced histamine-release in allergic patients 5 days after treatment with rhG-CSF .
Changes in maximal histamine release from the blood of S. mansoni-infected individuals 21-days after treatment
At 21-days post-treatment, SEA or anti-IgE stimulated histamine-releasability by the blood of most patients was still significantly lower than it was before treatment (Figure 2; SEA: p = 0.017, anti-IgE: p = 0.059). Thus, it appeared that the blood basophils were desensitized 1-day post-treatment and that, in relation to anti-IgE and SEA at least, this desensitised state was still evident 21-days after treatment. However, the absolute amount of released histamine was significantly higher at 21-days post-treatment compared with pre-treatment levels with SEA (p = 0.009), SWA (p = 0.000) or anti-IgE Ab (p = 0.008) stimulation (Figure 2 and Table 2). At 21-days post-treatment, histamine-releasability was not higher than pre-treatment % histamine-releasability, suggesting that the observed higher absolute amount of released histamine was the consequence of the up-regulation of total cellular histamine content.
At 21-days post-treatment there would have been few, if any, parasites remaining in the blood, and little or no parasite Ag in the circulation . For example, at this time-point CAA, a diagnostic schistosome gut-associated circulating Ag, could not be detected in the plasma of 98% of the treated individuals (data not shown). Thus, basophils present at 21-days post-treatment would not have been subject to in vivo Ag challenge prior to in vitro culture. In these circumstances the basophils would have reacted normally to in vitro Ag stimulation via surface receptor bound Abs, including IgE. However, the continued reduction in histamine-releasability 21-days post-treatment, compared with the infected pre-treatment state, suggests the presence of a, yet to be identified, infection-associated priming factor that is removed or becomes ineffective after treatment.
We examined the possibility that, alternatively, an Ag-specific desensitisation, comparable to the immuno-therapeutic desensitisation of allergic patients, could have occurred. A role for IL-10 and TNFα of T-cell origin has been postulated in basophil desensitisation after wasp venom immunotherapy , and these cytokines were detectable in the plasma at all time-points. We found however no correlation between the plasma concentration of these cytokines and histamine-releasability after treatment in this study cohort (data not shown). The mechanism down-regulating histamine-releasability at 21 days post-treatment is therefore likely to be different from the one involved in therapeutic immuno-desensitisation.
Comparison of SEA-, SWA- and anti-IgE-induced histamine-releasability
We assumed that anti-IgE would induce the highest possible IgE-dependent histamine-releasability and compared it to that of SEA and SWA, to assess the secretagogue potential of the parasite Ag. As shown in Figure 2, both SWA and SEA induced significantly higher histamine-releasability than anti-IgE Ab at all study time-points: SEA Vs anti-IgE pre-treatment p = 0.002 (n = 32); 1-day post-treatment p = 0.002 (n = 29), 21-days post-treatment p = 0.004 (n-25); SWA Vs anti-IgE pre-treatment p = 0.004 (n = 32), 1-day post-treatment p = 0.002 (n = 29), 21-days post-treatment p = 0.000 (n = 25). There was no statistically significant difference between histamine-releasability induced by SEA and that induced by SWA at pre-treatment and at 1 day post-treatment, but at 21 days post-treatment, SWA-induced histamine-releasability was significantly higher than SEA-induced histamine-releasability (p = 0.005, N = 25). Parasite factors, such as a S. mansoni analogue to human translationally controlled tumour protein (TCTP), may induce an additional IgE-independent histamine release, or enhanced non Ag-specific, IgE-dependent release [13, 31]. These non-classical pathways could therefore be involved in the additional histamine-release. However we didn't detect histamine-release from basophils from non-infected individuals after SEA or SWA stimulation under the same conditions. This enhanced histamine-releasability could then appear to be specifically induced by the experience of infection. We however have to consider the fact that our methodology may have been less sensitive than those used in the description of these non-classical pathways and that low levels of histamine-release in non-infected individuals may not have been detected. Thus, it is possible that parasite factors may have directly induced additional or enhanced histamine-releasability.
Post-treatment changes in in vitro basophil sensitivity to anti-IgE and parasite Ags
The sensitivity of blood cells to parasite Ag or anti-IgE stimulation was assessed by determining the lowest of the 9 concentrations of Ag or of the 3 concentrations of anti-IgE used in the assay, that was capable of triggering a significant histamine-release. The lower the concentration required, the higher the blood cell sensitivity. At 1-day post-treatment, the sensitivity of blood cells from most individuals was either unchanged (anti-IgE:15 out of 32, SEA:17 out of 32, SWA:12 out of 32) or had decreased (anti-IgE:13 out of 32, SEA:13 out of 32, SWA:13 out of 32), compared with the number of individuals with increased sensitivity for each stimuli (SEA p = 0.006, SWA p = 0.030 or anti-IgE Ab p = 0.026). This reduced sensitivity was parallel to the decline in histamine-release at 1-day post-treatment shown in Figure 2. This general decline in basophil sensitivity during the first 24-hours after treatment contrasted with an increase in sensitivity from 1-day to 21-days post-treatment. During this period, the sensitivity of blood cells from most individuals increased (anti-IgE:9 out of 25, SEA:12 out of 25, SWA:13 out of 25) or was unchanged (anti-IgE:14 out of 25, SEA:9 out of 25, SWA:8 out of 25) for SEA, SWA or anti-IgE Ab stimulation (p= 0.021, p = 0.010 and p = 0.024, respectively), mirroring the re-establishment of histamine-release at 21-days post-treatment shown above. When the changes in sensitivity between consecutive time-points were compared, significant or highly significant negative associations were found between the changes from pre-treatment to 1-day post-treatment and the changes from 1-day to 21-days post-treatment (r = -0.636, p = 0.001 for anti-IgE; r = -0.568, p = 0.003 for SEA; r = -0.465, p = 0.019 for SWA; n = 25, for all conditions). Thus, the individuals whose basophil sensitivity decreased from pre-treatment to 1-day post-treatment tended to be the same individuals whose basophil sensitivity had increased by 21-days post-treatment.
Whereas histamine-releasability shows the potential strength of histamine-release, sensitivity reflects the Ag concentration required to induce degranulation. In a mouse experimental model, sensitivity, contrarily to histamine-releasability, was shown to be correlated to affinity of the IgE for the Ag . This reduced sensitivity to Ag or anti-IgE Ab could reflect qualitative rather than quantitative changes in plasma antibodies. The parallel changes in histamine-releasability and in basophil sensitivity show that reduced basophil sensitivity could be partly responsible for the post-treatment reduction in histamine-releasability in blood culture after treatment.
The lack of relationship between anti-IgE- and Ag-induced histamine-releasability, and plasma total IgE, specific IgE and specific IgG4
Plasma levels of total IgE, anti-SEA and anti-SWA IgE and IgG4 were measured at the 3 study time points. Histamine-releasability was not associated with level of total IgE at any time-point. Indeed, despite a statistically significant increase in total IgE between pre-treatment and 21-days post-treatment (p = 0.024, N= 24), anti-IgE stimulated histamine-releasability was lower in the blood of most patients at 21-days post-treatment. Histamine-releasability was associated with parasite-specific plasma IgE levels only for SEA-induced histamine-release with anti-SEA IgE at 1-day post-treatment (r = 0.513, p = 0.012, n = 23), when histamine-releasability was at its lowest. There was no statistically significant change in plasma anti-SEA IgE between pre-treatment and 1-day post-treatment, as shown in Figure 3, while there was a very significant decrease in SEA-induced histamine-releasability. No significant correlation between IgG4 levels and SEA or SWA Ag-stimulated histamine-releasability was found. Thus it would appear that post-treatment changes in the level of histamine-releasability in vitro were regulated either at the cellular level or by serum factors affecting the in vivo sensitisation, priming or neutralisation of the basophils or of other surface-bound factors, other than ELISA-detectable parasite-specific IgE or IgG4. A similar lack of relationship between plasma Ab and histamine-release has been reported from studies of cord-blood basophils passively-sensitized with plasma from S. mansoni infected adults  and RBL-2H3 cells transfected with FcεRI sensitized with plasma from allergic patients .
The influence of pre-treatment infection intensity on post-treatment anti-IgE- and Ag-induced histamine releasability
Although the relationship between infection and low post-treatment histamine-releasability could result from an infection intensity-dependent down-regulation mechanism there is a particularly interesting alternative explanation. It has been suggested from studies in the murine model of schistosomiasis that parasite induced histamine-release may regulate the intensity of schistosome infection by triggering inflammation reactions that prevent super-infection . In relation to the present study, it is possible that a high histamine-releasability response to parasite Ag might be protective against infection/re-infection. If this were true, the association between low infection intensity and high histamine-releasability would result in a restriction of parasite numbers by an IgE-dependent histamine-release, not intense infection suppressing histamine-release. With regard to this hypothesis, it would be interesting to test if the magnitude of in vitro histamine-releasability in response to treatment was predictive of the subsequent resistance or susceptibility of individuals to re-infection with S. mansoni.
The present work describes changes in basophils biology and the modulation of basophil function, induced by the treatment of S. mansoni infection. Some of these changes may be a return to steady non-infected state. S. mansoni treatment-induced human basophil immune modulation is associated with pre-treatment infection intensity. The mechanisms involved in post-treatment basophil desensitisation at 1-day post-treatment may have similarities to those that induce desensitisation to allergens with immunotherapy. Analysis of histamine-release from naïve basophils passively sensitised with the plasma from the same individuals should provide data on the plasma factors involved in the regulation of the basophil response. It is hoped that such studies, coupled to the monitoring of reinfection after treatment, will provide detailed information about the role of basophils in IgE mediated immunological protection against reinfection after treatment and mechanisms by which the potential adverse effects of IgE-mediated immune effector mechanisms are down-regulated.
Study cohort selection
A cohort of forty individuals was selected in the fishing village of Bugoigo, on the Eastern Shore of Lake Albert, Masindi District, Uganda. Vegetation in the shallow parts of the lake was an ideal habitat for snails of the genus Biomphalaria, particularly B. sudanica and B. stanleyi, the two intermediate host species of S. mansoni in this area. Adult men were, through their occupation, the part of the population the most exposed to infection. The select study group comprised males aged between 18 and 45 years old (mean age 34.5 years), having resided in Bugoigo for at least three years and consenting to participate. The selection was made after parasitological examination of three stool samples per individual, with two Kato thick smears per sample using 50 mg of faeces per slide . All the selected individuals had detectable S. mansoni eggs, but those with over 70 eggs per slide were excluded to reduce the number of outliers. The mean pre-treatment egg count for the selected cohort was 282 (range = 983) eggs per gram of faeces.
A group of 8 healthy volunteers, members of the sample collection team, was bled at the same time as the third bleed of the study group. This control group comprised 5 Africans (2 females and 3 males) and 3 Europeans (1 female and 2 males).
Blood collection and PZQ treatment
Informed consent was obtained from all those who participated in this study, in line with the National guidelines of the Ugandan Ministry of Health, whose ethical review committees approved all the protocols used, and the US Department of Health and Human Services. Thirty ml-blood samples taken by venipuncture in heparinised syringes (10 U/ml heparin Na salt, Sigma, UK) were collected from the 33 participants before they received a single dose of 40 mg/kg body weight of PZQ. The participants were asked to come back to donate blood samples a second time (1-day post-treatment) exactly 24 hours after having been treated. A third sample was taken 21-days post-treatment from the 28 participants who came back to donate blood. Only 3 ml of the collected blood was used for histamine assays. The rest of the blood was used for other assays that were parts of the same main study. At the completion of this study the whole Bugoigo community was treated with PZQ.
Antigen coating of microtitre plates used for histamine release
Glass fibre microtitre plates from Ref Lab, Denmark were coated with 25 μl of the following substances:
Histamine (50 ng/ml) added to four wells; α-IgE from DAKO, Denmark, used in three concentrations (1:200 (7 μg/ml), 1:1000, 1:2000), each concentration was added in two wells; SEA and SWA, used in nine concentrations with the dilution factor 3.5 and each concentration was added into two wells. The highest concentration of SEA and SWA was 50 μg/ml. All dilutions were made in distilled water containing 5% glycerol. Subsequently the allergen coated microtitre plates were dried for 6 hours at 37°C, and thereafter the plates were packed and sealed until use in Bugoigo. Preliminary experiments using blood from 3 S. mansoni-infected patients showed that histamine-release performed in Ag-coated plates (stored for 3 months at 20°C) varied less than 5% from histamine release induced by freshly prepared Ag. Control experiments using blood from 5 non-infected individuals showed no histamine-release to SEA and SWA (data not shown).
Histamine release assay
Histamine-release was performed using the glass fibre assay described elsewhere , which allows the capture of released histamine, irrespective of basophil source, after stimulation. The assay was however simplified for direct release of histamine by peripheral blood without passive sensitisation. In brief 3 ml of each blood sample was washed twice in PIPES buffer (Ref Lab, Denmark) at room temperature to eliminate platelets and plasma factors not already cell-bound. The samples were reconstituted to the initial volume with PIPES buffer and thereafter referred to as "washed blood", with the addition of IL-3 (5 ng/ml washed blood). Substances in the Ag-coated plates were dissolved by adding 25 μl PIPES buffer to each well prior to addition of 25 μl washed blood per well. Histamine was released and subsequently bound to glass fibres in the microtitre plate. Thereafter the plate was washed with distilled water. The plates were stored in the dark at room temperature during the 21-days study period in Bugoigo and subsequently shipped to the Ref Lab for histamine analysis.
Histamine was measured by spectrofluorometry as described elsewhere. Spontaneous release is automatically subtracted with plate background from measured data by the analysis software.
S. mansoni worms and eggs for Ag preparation were obtained from mice infected with 250 S. mansoni cercariae. Forty-two days after infection mice were injected s.c. with hydrocortisone acetate (2.5 mg/mouse), to reduce granuloma formation around the eggs in the livers. 49-days post-infection, the portal blood of infected mice were perfused to recover the worms, as described previously . Recovered worms were frozen in droplets in liquid nitrogen and stored in liquid nitrogen until use. PBS soluble extract of adult worm Ag (SWA) was prepared by recovering the lipid-free supernatant fraction of the finely crushed frozen worms after centrifugation for one hour at 10,000 g at 4°C as described previously . Soluble egg Ag (SEA) was the supernatant fluid obtained after S. mansoni eggs were homogenised in PBS as described previously  except that the homogenisation step was done by sonication. Both SWA and SEA were filtered through sterile 0.22 μm pore-size filters and endotoxin content was measured using the Limulus Amebocyte Lysate Kit (QCL-1000, Biowhittaker Inc, Walkersville, MD, USA). The levels of endotoxin in the native Ag used in these studies were as follows 10.7 ng endotoxin /mg SEA and 25 ng endotoxin /mg SWA. Whole blood cultures in the presence of these levels of endotoxin induced neither cell activation, nor cytokine release (data not shown).
Specific antibody determination
A semi-quantitative measurement of SEA- and SWA- specific IgE and IgG4 isotypes was carried out on the plasma of the study individuals by ELISA as described previously . Briefly, SEA-specific and SWA-specific antibodies were captured in Immulon-2 flat bottom plates (Dynex) coated with SEA and SWA, respectively. Detection of IgG4 and IgE was done by use of mouse anti-human IgG4 clone RJ4 (Skybio Ltd, UK) and mouse anti-human IgE clone HP 6029 (CN Biosciences, UK), respectivelyThe assays were developed using biotinylated sheep anti-mouse Ig followed by streptavidin-biotin-HRP complex (both reagents from A P Biotech) and by incubation with O-phenylenediamine (OPD). Optical densities (OD) were read at 490 nm. Samples from the 3 time-points were processed at the simultaneously to allow for comparison of OD.
Total IgE determination
Total IgE were quantified in the plasma of the study individuals by in-house sandwich ELISA. Both antibodies were obtained from Pharmingen. Mouse anti-human IgE clone G7-18 was used for capture in Immulon 2 flat bottom plates (Dynex). Detection was made with biotinylated mouse anti-human IgE clone G7-26, with poly-HRP (CLB) amplification and incubation with OPD. Sample plasmas and human IgE myeloma standards (Calbiochem) were diluted in 10% animal sera (an equivolume mix of complement-inactivated sera from mouse, rat, goat and fetal bovine) to block heterophilic antibodies.
CAA was quantified in the plasma of the study individuals by ELISA, after modification of the method described by Deelder and colleagues . The modification consisted in using different anti-CAA antibodies as those reported in the original article. Both capture and detection antibodies were provided by Dr G.J. van Dam and Prof. A.M. Deelder, University of Leiden, the Netherlands. In summary, trichloroacetic acid-treated samples or standards (TCA soluble SWA)  were incubated in Immulon 2 HB plates (Dynex) coated with mouse anti-CAA antibody clone 147-39A and captured CAA was detected with biotinylated mouse anti-CAA clone 147-3G4. Incubations with alkaline phospatase-conjugated streptavidin (Dako) and the chromogenic substrate pNPP (Sigma) allowed reading at 405 nm.
For each Ag or anti-IgE Ab stimulus, the amount of histamine released at the stimulus concentration that induced the highest release was defined as the maximal histamine-release. The sensitivity was defined as the lowest stimulus concentration required to induce a histamine-release equal or greater to 10 ng/ml. This threshold represents 2 standard deviations from the average histamine quantification using a blank sample. Statistical analysis with non parametric tests was done with SPSS 10 for Macintosh: comparisons of related variables were made using Wilconxon's ranks test, independent variables were compared using Mann-Whitney U test and correlations between variables were made using Spearman's test.
circulating anodic antigen
S. mansoni Soluble Egg Antigen
S. mansoni Soluble Worm Antigen.
The studies reported here were given financial support from the British Medical Research Council, the Wellcome Trust and The Commission of the European Community's, Science and Technology for Development Programme (INCO-DC contract IC18 CT97-0237 and INCO-DEV contract ICA4-CT-1999-10003) ".
- Roberts M, Butterworth AE, Kimani G, Kamau T, Fulford AJ, Dunne DW, Ouma JH, Sturrock RF: Immunity after treatment of human schistosomiasis: association between cellular responses and resistance to reinfection. Infect Immun. 1993, 61: 4984-4993.PubMed CentralPubMedGoogle Scholar
- Medhat A, Shehata M, Bucci K, Mohamed S, Dief AD, Badary S, Galal H, Nafeh M, King CL: Increased interleukin-4 and interleukin-5 production in response to Schistosoma haematobium adult worm antigens correlates with lack of reinfection after treatment. J Infect Dis. 1998, 178: 512-519.View ArticlePubMedGoogle Scholar
- Hagan P, Blumenthal UJ, Chaudri M, Greenwood BM, Hayes RJ, Hodgson I, Kelly C, Knight M, Simpson AJ, Smithers SR, et al.: Resistance to reinfection with Schistosoma haematobium in Gambian children: analysis of their immune responses. Trans R Soc Trop Med Hyg. 1987, 81: 938-946. 10.1016/0035-9203(87)90359-2.View ArticlePubMedGoogle Scholar
- Hagan P, Blumenthal UJ, Dunn D, Simpson AJ, Wilkins HA: Human IgE, IgG4 and resistance to reinfection with Schistosoma haematobium. Nature. 1991, 349: 243-245. 10.1038/349243a0.View ArticlePubMedGoogle Scholar
- Rihet P, Demeure CE, Bourgois A, Prata A, Dessein AJ: Evidence for an association between human resistance to Schistosoma mansoni and high anti-larval IgE levels. Eur J Immunol. 1991, 21: 2679-2686.View ArticlePubMedGoogle Scholar
- Zhang Z, Wu H, Chen S, Hu L, Xie Z, Qiu Y, Su C, Cao JP, Wu Y, Zhang S, Wu G: Association between IgE antibody against soluble egg antigen and resistance to reinfection with Schistosoma japonicum. Trans R Soc Trop Med Hyg. 1997, 91: 606-608. 10.1016/S0035-9203(97)90047-X.View ArticlePubMedGoogle Scholar
- Dunne DW, Butterworth AE, Fulford AJ, Kariuki HC, Langley JG, Ouma JH, Capron A, Pierce RJ, Sturrock RF: Immunity after treatment of human schistosomiasis: association between IgE antibodies to adult worm antigens and resistance to reinfection. Eur J Immunol. 1992, 22: 1483-1494.View ArticlePubMedGoogle Scholar
- Webster M, Fulford AJ, Braun G, Ouma JH, Kariuki HC, Havercroft JC, Gachuhi K, Sturrock RF, Butterworth AE, Dunne DW: Human immunoglobulin E responses to a recombinant 22.6-kilodalton antigen from Schistosoma mansoni adult worms are associated with low intensities of reinfection after treatment. Infect Immun. 1996, 64: 4042-4046.PubMed CentralPubMedGoogle Scholar
- Capron M, Capron A: Effector functions of eosinophils in schistosomiasis. Mem Inst Oswaldo Cruz. 1992, 87 Suppl 4: 167-170.View ArticlePubMedGoogle Scholar
- Clegg JA, Smithers SR, Terry RJ: Acquisition of human antigens by Schistosoma mansoni during cultivation in vitro. Nature. 1971, 232: 653-654.View ArticlePubMedGoogle Scholar
- Moser G, Wassom DL, Sher A: Studies of the antibody-dependent killing of schistosomula of Schistosoma mansoni employing haptenic target antigens. I. Evidence that the loss in susceptibility to immune damage undergone by developing schistosomula involves a change unrelated to the masking of parasite antigens by host molecules. J Exp Med. 1980, 152: 41-53.View ArticlePubMedGoogle Scholar
- Schramm G, Falcone FH, Gronow A, Haisch K, Mamat U, Doenhoff MJ, Oliveira G, Galle J, Dahinden CA, Haas H: Molecular characterization of an interleukin-4-inducing factor from Schistosoma mansoni eggs. J Biol Chem. 2003, 278: 18384-18392. 10.1074/jbc.M300497200.View ArticlePubMedGoogle Scholar
- Rao KV, Chen L, Gnanasekar M, Ramaswamy K: Cloning and characterization of a calcium-binding, histamine-releasing protein from Schistosoma mansoni. J Biol Chem. 2002, 277: 31207-31213. 10.1074/jbc.M204114200.PubMed CentralView ArticlePubMedGoogle Scholar
- Araujo MI, Lopes AA, Medeiros M, Cruz AA, Sousa-Atta L, Sole D, Carvalho EM: Inverse association between skin response to aeroallergens and Schistosoma mansoni infection. Int Arch Allergy Immunol. 2000, 123: 145-148. 10.1159/000024433.View ArticlePubMedGoogle Scholar
- van den Biggelaar AH, van Ree R, Rodrigues LC, Lell B, Deelder AM, Kremsner PG, Yazdanbakhsh M: Decreased atopy in children infected with Schistosoma haematobium: a role for parasite-induced interleukin-10. Lancet. 2000, 356: 1723-1727. 10.1016/S0140-6736(00)03206-2.View ArticlePubMedGoogle Scholar
- Leopold G, Ungethum W, Groll E, Diekmann HW, Nowak H, Wegner DH: Clinical pharmacology in normal volunteers of praziquantel, a new drug against schistosomes and cestodes. An example of a complex study covering both tolerance and pharmacokinetics. Eur J Clin Pharmacol. 1978, 14: 281-291.View ArticlePubMedGoogle Scholar
- Fallon PG, Fookes RE, Wharton GA: Temporal differences in praziquantel- and oxamniquine-induced tegumental damage to adult Schistosoma mansoni: implications for drug-antibody synergy. Parasitology. 1996, 112 (Pt 1): 47-58.View ArticleGoogle Scholar
- Berhe N, Gundersen SG, Abebe F, Birrie H, Medhin G, Gemetchu T: Praziquantel side effects and efficacy related to Schistosoma mansoni egg loads and morbidity in primary school children in north-east Ethiopia. Acta Trop. 1999, 72: 53-63. 10.1016/S0001-706X(98)00084-9.View ArticlePubMedGoogle Scholar
- Ottesen EA, Poindexter RW, Hussain R: Detection, quantitation, and specificity of antiparasite IgE antibodies in human schistosomiasis mansoni. Am J Trop Med Hyg. 1981, 30: 1228-1237.PubMedGoogle Scholar
- Derouin F, Rouveix B, Sarfati C: IgE response and histamine release in chronic human schistosomiasis. Biomed Pharmacother. 1985, 39: 32-35.PubMedGoogle Scholar
- Stevens WJ, Feldmeir H, Bridts CH, Daffalla AA: IgG and IgE circulating immune complexes, total serum IgE and parasite related IgE in patients with mono- or mixed infection with Schistosoma mansoni and/or S. haematobium. Influence of therapy. Clin Exp Immunol. 1983, 52: 144-152.PubMed CentralPubMedGoogle Scholar
- Wittig HJ, Belloit J, De Fillippi I, Royal G: Age-related serum immunoglobulin E levels in healthy subjects and in patients with allergic disease. J Allergy Clin Immunol. 1980, 66: 305-313.View ArticlePubMedGoogle Scholar
- Moverare R, Vesterinen E, Metso T, Sorva R, Elfman L, Haahtela T: Pollen-specific rush immunotherapy: clinical efficacy and effects on antibody concentrations. Ann Allergy Asthma Immunol. 2001, 86: 337-342.View ArticlePubMedGoogle Scholar
- Petersson BA, Stalenheim G: Induction of histamine release and densensitization in human leukocytes. Scand J Immunol. 1975, 4: 103-112.View ArticlePubMedGoogle Scholar
- Mendoza GR, Minagawa K: Subthreshold and suboptimal desensitization of human basophils. II. Nonspecificity and irreversibility of desensitization. Int Arch Allergy Appl Immunol. 1982, 69: 282-284.View ArticlePubMedGoogle Scholar
- Dembo M, Goldstein B: A model of cell activation and desensitization by surface immunoglobin: the case of histamine release from human basophils. Cell. 1980, 22: 59-67. 10.1016/0092-8674(80)90154-3.View ArticlePubMedGoogle Scholar
- Tedeschi A, Lorini M, Arquati M, Miadonna A: Regulation of histamine release from human basophil leucocytes: role of H1, H2 and H3 receptors. Allergy. 1991, 46: 626-631.View ArticlePubMedGoogle Scholar
- Pedersen M, Kristensen KS, Clementsen P, Olsen OT, Skov PS, Permin H, Norn S: Increased numbers of circulating basophils with decreased releasability after administration of rhG-CSF to allergic patients. Agents Actions. 1994, 41 Spec No: C24-5.View ArticlePubMedGoogle Scholar
- de Jonge N, De Caluwe P, Hilberath GW, Krijger FW, Polderman AM, Deelder AM: Circulating anodic antigen levels in serum before and after chemotherapy with praziquantel in schistosomiasis mansoni. Trans R Soc Trop Med Hyg. 1989, 83: 368-372. 10.1016/0035-9203(89)90507-5.View ArticlePubMedGoogle Scholar
- Pierkes M, Bellinghausen I, Hultsch T, Metz G, Knop J, Saloga J: Decreased release of histamine and sulfidoleukotrienes by human peripheral blood leukocytes after wasp venom immunotherapy is partially due to induction of IL-10 and IFN-gamma production of T cells. J Allergy Clin Immunol. 1999, 103: 326-332.View ArticlePubMedGoogle Scholar
- Haisch K, Schramm G, Falcone FH, Alexander C, Schlaak M, Haas H: A glycoprotein from Schistosoma mansoni eggs binds non-antigen-specific immunoglobulin E and releases interleukin-4 from human basophils. Parasite Immunol. 2001, 23: 427-434. 10.1046/j.1365-3024.2001.00392.x.View ArticlePubMedGoogle Scholar
- Mita H, Yasueda H, Akiyama K: Affinity of IgE antibody to antigen influences allergen-induced histamine release. Clin Exp Allergy. 2000, 30: 1583-1589. 10.1046/j.1365-2222.2000.00921.x.View ArticlePubMedGoogle Scholar
- Marchand F, Mecheri S, Guilloux L, Iannascoli B, Weyer A, Blank U: Human serum IgE-mediated mast cell degranulation shows poor correlation to allergen-specific IgE content. Allergy. 2003, 58: 1037-1043. 10.1034/j.1398-9995.2003.00251.x.View ArticlePubMedGoogle Scholar
- Eich-Wanger C, Muller UR: Bee sting allergy in beekeepers. Clin Exp Allergy. 1998, 28: 1292-1298. 10.1046/j.1365-2222.1998.00411.x.View ArticlePubMedGoogle Scholar
- Gerken SE, Vaz NM, Mota-Santos TA: Local anaphylactic reactions to the penetration of cercariae of Schistosoma mansoni. Braz J Med Biol Res. 1990, 23: 275-281.PubMedGoogle Scholar
- Katz N, Chaves A, Pellegrino J: A simple device for quantitative stool thick-smear technique in Schistosomiasis mansoni. Rev Inst Med Trop Sao Paulo. 1972, 14: 397-400.PubMedGoogle Scholar
- Satti MZ, Ebbesen F, Vennervald B, Lind P, Ghalib H, Sulaiman S, Daffalla A, Skov PS: Use of a new glass microfibre histamine release method to study the modulation of the host response in human schistosomiasis mansoni. Individuals with different degrees of exposure to the disease show differing antibody biological function. Trop Med Int Health. 1996, 1: 655-666.View ArticlePubMedGoogle Scholar
- Smithers SR, Terry RJ: The infection of laboratory hosts with cercariae of Schistosoma mansoni and the recovery of the adult worms. Parasitology. 1965, 55: 695-700.View ArticlePubMedGoogle Scholar
- Webster M, Libranda-Ramirez BD, Aligui GD, Olveda RM, Ouma JH, Kariuki HC, Kimani G, Olds GR, Fulford AJ, Butterworth AE, Dunne DW: The influence of sex and age on antibody isotype responses to Schistosoma mansoni and Schistosoma japonicum in human populations in Kenya and the Philippines. Parasitology. 1997, 114 ( Pt 4): 383-393. 10.1017/S003118209600858X.View ArticleGoogle Scholar
- Dunne DW, Lucas S, Bickle Q, Pearson S, Madgwick L, Bain J, Doenhoff MJ: Identification and partial purification of an antigen (omega 1) from Schistosoma mansoni eggs which is putatively hepatotoxic in T-cell deprived mice. Trans R Soc Trop Med Hyg. 1981, 75: 54-71. 10.1016/0035-9203(81)90013-4.View ArticlePubMedGoogle Scholar
- Deelder AM, De Jonge N, Boerman OC, Fillie YE, Hilberath GW, Rotmans JP, Gerritse MJ, Schut DW: Sensitive determination of circulating anodic antigen in Schistosoma mansoni infected individuals by an enzyme-linked immunosorbent assay using monoclonal antibodies. Am J Trop Med Hyg. 1989, 40: 268-272.PubMedGoogle Scholar
- De Jonge N, Fillie YE, Deelder AM: A simple and rapid treatment (trichloroacetic acid precipitation) of serum samples to prevent non-specific reactions in the immunoassay of a proteoglycan. J Immunol Methods. 1987, 99: 195-197. 10.1016/0022-1759(87)90127-X.View ArticlePubMedGoogle Scholar
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