Changes in IgE- and Antigen-dependent histamine-release in peripheral blood of Schistosoma mansoni-infected Ugandan fishermen after treatment with praziquantel

Satti, Mohamed Z; Cahen, P; Skov, Per Stahl; Joseph, Sarah; Jones, Frances M.; Fitzsimmons, Colin M.; Hoffmann, Karl F.; Reimert, Claus M.; Kariuki, H. Curtis; Kazibwe, Francis; Mwatha, Joseph K.; Kimani, Gachuhi; Vennervald, Birgitte J.; Ouma, John H.; Kabatereine, Narcis B.; Dunne, David W.

doi:10.1186/1471-2172-5-6

Cited by 17 publications

(9 citation statements)

References 40 publications

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“…For example, adult S. mansoni -antigen-induced HR from basophils passively sensitized with human infection sera increased post-treatment and suggested that IgG4-mediated down-regulation occurred during active infection [28]. We also observed increases in α-IgE-, SEA-, and SWA-HR in washed basophils from Ugandan fishermen exposed to S. mansoni [27], whereas Larson et al [33] reported increases in nonspecific IgE-dependent and IgE-independent HR in washed basophils following anthelmintic treatment of a small sample of Ascaris lumbricoides- and Trichuris trichiura -infected children.…”

Section: Discussionmentioning

confidence: 82%

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Suppression of Basophil Histamine Release and Other IgE-dependent Responses in Childhood Schistosoma mansoni/hookworm Coinfection

Moira

Fitzsimmons

Jones

et al. 2014

Journal of Infectious Diseases

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Background. The poor correlation between allergen-specific immunoglobulin E (asIgE) and clinical signs of allergy in helminth infected populations suggests that helminth infections could protect against allergy by uncoupling asIgE from its effector mechanisms. We investigated this hypothesis in Ugandan schoolchildren coinfected with Schistosoma mansoni and hookworm.Methods. Skin prick test (SPT) sensitivity to house dust mite allergen (HDM) and current wheeze were assessed pre-anthelmintic treatment. Nonspecific (anti-IgE), helminth-specific, and HDM-allergen-specific basophil histamine release (HR), plus helminth- and HDM-specific IgE and IgG4 responses were measured pre- and post-treatment.Results. Nonspecific- and helminth-specific-HR, and associations between helminth-specific IgE and helminth-specific HR increased post-treatment. Hookworm infection appeared to modify the relationship between circulating levels of HDM-IgE and HR: a significant positive association was observed among children without detectable hookworm infection, but no association was observed among infected children. In addition, hookworm infection was associated with a significantly reduced risk of wheeze, and IgG4 to somatic adult hookworm antigen with a reduced risk of HDM-SPT sensitivity. There was no evidence for S. mansoni infection having a similar suppressive effect on HDM-HR or symptoms of allergy.Conclusions. Basophil responsiveness appears suppressed during chronic helminth infection; at least in hookworm infection, this suppression may protect against allergy.

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Section: Discussionmentioning

confidence: 82%

“…HR assays followed a similar protocol to that described previously [ 27 ] but with the washing stage omitted, thus measuring direct HR by unwashed whole blood. Briefly, 25 µL of PIPES buffer was added to each well of glass fiber-coated microtitre antigen-coated plates to dissolve antigen, followed by 25 µL of unwashed whole blood.…”

Section: Methodsmentioning

confidence: 99%

Suppression of Basophil Histamine Release and Other IgE-dependent Responses in Childhood Schistosoma mansoni/hookworm Coinfection

Moira

Fitzsimmons

Jones

et al. 2014

Journal of Infectious Diseases

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“…Such studies involve documentation of cases of schistosomiasis, their treatment and cure, and examinations at a later date to see if reinfections occurred [1],[2],[3],[4]. Of all the immunologic findings associated with these investigations, the most consistent observation is that resistance (usually defined as lower levels of infection) correlates with high IgE and low IgG4 antibodies against schistosome antigens [5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18]. Other studies have reported that production of IFN-γ and IL-5 to schistosome antigens are also correlated with resistance [19],[20],[21],[22].…”

Section: Introductionmentioning

confidence: 99%

Association of the Gene Polymorphisms IFN-γ +874, IL-13 −1055 and IL-4 −590 with Patterns of Reinfection with Schistosoma mansoni

et al. 2009

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BackgroundThe immunologic findings that most consistently correlate with resistance in human schistosomiasis are high levels of IgE and low levels of IgG4. We have genotyped gene and promoter polymorphisms of cytokines associated with regulation of these isotypes in a cohort of men occupationally exposed to Schistosoma mansoni in western Kenya and evaluated their patterns with respect to resistance and susceptibility to reinfection after treatment and cure with praziquantel (PZQ).Methodology/Principal FindingsIn this cohort, polymorphisms in IL-4 (−590T high IgE), IL-13 (−1055T high producer) and IFN-γ (+874A high producer) demonstrated several correlations with resistance to reinfection. Resistance to reinfection was significantly correlated with the heterozygous IL-4 −590 genotype C/T (OR 3.5, [CI 1.2, 10.2]) compared to T/T. Among men with a homozygous IL-13 genotype CC/TT, having a T allele at the IFN-γ +874 position increased the odds of resistance relative to individuals with the IFN-γ +874 A/A genotype (OR = 17.5 [CI 3.0, 101.5]). Among men with homozygous A/A IFN-γ genotype, the heterozygous IL-13 genotype C/T was associated with resistance relative to the homozygous C/C or T/T genotypes (OR = 22.5 [CI 3.5, 144.4]). No increases in odds of resistance were found in relation to the IL-13 genotype among those with a T allele in the IFN-γ gene or in relation to the IFN-γ genotype among those with a heterozygous IL-13 genotype. Calculation of the attributable proportion of resistance showed a significant synergistic interaction between IL-13 −1055 C/T and IL-4 −590 C/T.ConclusionsThe identified polymorphisms do not by themselves confer resistance or susceptibility, but we propose that these genotypes allow the resistant phenotype to be developed and expressed upon suitable immune exposure. Based on the literature, these polymorphisms contribute to the regulation of their respective cytokines, likely leading to downstream differences in the production and interrelationships of critical defense mechanisms.

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“…Bearing in mind that schistosomiasis is a disease caused by intravascular worms, inhibition of active basophil degranulation may be necessary to prevent excessive allergic-like responses in the bloodstream. Interestingly, suppression of basophil function may be vital during PZQ treatment, which induces a massive allergic-like response upon the death of adult worms, with relatively few clinical symptoms (8, 62). …”

Section: 0 Discussionmentioning

confidence: 99%

Immuno-evasive tactics by schistosomes identify an effective allergy preventative

Griffith

Liang

Whitworth

et al. 2015

Experimental Parasitology

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Many chronic inflammatory diseases can be improved by helminth infection, but the mechanisms are poorly understood. Allergy and helminthiasis are both associated with Th2-like immune responses; thus, defining how infection with parasites leads to reduced allergy has been particularly challenging. We sought to better understand this conundrum by evaluating host-parasite interactions involved in Th2 immunity in human schistosomiasis. Immune cells were cultured with schistosomes and the effect on CD23, an IgE receptor associated with resistance in schistosomiasis, was evaluated. Cells treated with schistosomes demonstrated reduced surface CD23 levels with a parallel accumulation of soluble (s) CD23 suggesting this IgE receptor is proteolytically cleaved by the parasite. Consistent with this hypothesis, a schistosome-generated (SG)-sCD23 fragment of 15kDa was identified. SG-sCD23 inhibited IgE from binding to CD23 and FcεRI, but lacked the ability to bind CD21. These results suggested that schistosomes target IgE-mediated immunity in immuno-evasive tactics. Based on its characteristics, we predicted that SG-sCD23 would function as an efficacious allergy preventative. Treatment of human FcεRI-transgenic mice with recombinant (r) SG-sCD23 reduced the ability of human IgE to induce an acute allergic response in vivo. In addition, an optimized form of rSG-sCD23 with an introduced point mutation at Asp258 (D258E) to stabilize IgE binding had increased efficacy compared to native rSG-sCD23. Schistosome infection may thus inhibit allergic-like protective immune responses by increasing soluble IgE decoy receptors. Allergy treatments based on this naturally occurring phenomenon may be highly effective and have fewer side effects with long-term use.

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Changes in IgE- and Antigen-dependent histamine-release in peripheral blood of Schistosoma mansoni-infected Ugandan fishermen after treatment with praziquantel

Cited by 17 publications

References 40 publications

Suppression of Basophil Histamine Release and Other IgE-dependent Responses in Childhood Schistosoma mansoni/hookworm Coinfection

Suppression of Basophil Histamine Release and Other IgE-dependent Responses in Childhood Schistosoma mansoni/hookworm Coinfection

Association of the Gene Polymorphisms IFN-γ +874, IL-13 −1055 and IL-4 −590 with Patterns of Reinfection with Schistosoma mansoni

Immuno-evasive tactics by schistosomes identify an effective allergy preventative

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