α-Gal specific-IgE prevalence and levels in Ecuador and Kenya: Relation to diet, parasites, and IgG4.

BACKGROUND: IgE to α-Gal is a cause of mammalian meat allergy and has been linked to tick bites in North America, Australia, and Eurasia. Reports from the developing world indicate that α-Gal sensitization is prevalent but has been little investigated. OBJECTIVE: We sought evidence for the cause(s) of α-Gal sensitization and lack of reported meat allergy among children in less developed settings in Ecuador and Kenya. METHODS: IgE to α-Gal and total IgE were assessed in children from Ecuador (n = 599) and Kenya (n = 254) and compared with children with (n = 42) and without known (n = 63) mammalian meat allergy from the southeastern United States. Information on diet, potential risk factors, and helminth infections was available for children from Ecuador. IgG4 to α-Gal and antibodies to regionally representative parasites were assessed in a subset of children. RESULTS: In Ecuador (32%) and Kenya (54%), α-Gal specific IgE was prevalent, but levels were lower than in children with meat allergy from the United States. Sensitization was associated with rural living, antibody markers of Ascaris exposure, and total IgE, but not active infections with Ascaris or Trichuris species. In Ecuador, 87.5% reported consuming beef at least once per week, including 83.9% of those who had α-Gal specific IgE. Levels of α-Gal specific IgG4 were not high in Ecuador, but were greater than in children from the United States. CONCLUSIONS: These results suggest that in areas of the developing world with endemic parasitism, α-Gal sensitization is (1) common, (2) associated with Ascaris exposure, and (3) distinguished by a low percentage of specific/total IgE compared with individuals with meat allergy in the United States.

IgE Levels to Ascaris and House Dust Mite Allergens Are Associated With Increased Histone Acetylation at Key Type-2 Immune Genes.

Background: Epigenetic changes in response to allergen exposure are still not well understood. The aim of this study was to evaluate histone acetylation levels in peripheral blood leukocytes from humans naturally infected by intestinal parasites and perennially exposed to house dust mites (HDM). Methods: Peripheral blood mononuclear cells (PBMCs) were isolated by gradient centrifugation from 20 infected and 21 non-infected individuals living in a rural/village in Colombia. Histone 3 acetylation (H3Ac) and histone 4 acetylation (H4Ac) levels were measured in six immune genes previously associated with helminth immunity by chromatin immunoprecipitation (ChIP)-quantitative PCR. Then we analyzed the association between histone acetylation levels with total parasite egg burden and IgE levels. Results: We found an inverse correlation between H4Ac levels in the IL13 gene and egg worm burden that remained significant after adjustment by age [-0.20 (-0.32 to -0.09), p < 0.0001]. Moreover, we found significant associations between H4Ac levels in IL4 [0.32 (0.05-0.60), p = 0.02] and CHI3L1 [0.29 (0.08-0.51), p = 0.008] with the IgE levels to Ascaris lumbricoides. In addition, the levels of specific IgE antibodies to HDM were associated with H4Ac levels in the gene TNFSF13B encoding the B cell activating factor (BAFF) [0.51 (0.26-0.76), p < 0.001]. All values are presented as beta (95% CI). Conclusion: Histone acetylation levels at key type-2 immune genes in humans were modified by nematode infection and HDM allergens and are associated with the intensity of the IgE response.

Ascariasis as a model to study the helminth/allergy relationships.

Ascariasis is the most frequent soil transmitted helminthiasis and, as well as other helminth infections, is expected to influence the clinical presentation of allergic diseases such as asthma. Indeed, several clinical and experimental works have shown an important impact either increasing or suppressing symptoms, and the same effects have been detected on the underlying immune responses. In this review we analyze the work on this field performed in Colombia, a Latin American tropical country, including aspects such as the molecular genetics of the IgE response to Ascaris; the allergenic activity of Ascaris IgE-binding molecular components and the immunological and clinical influences of ascariasis on asthma. The analysis allows us to conclude that the impact of ascariasis on the inception and evolution of allergic diseases such as asthma deserves more investigation, but advances have been made during the last years. The concurrent parasite-induced immunostimulatory and immunosuppressive effects during this helminthiasis do modify the natural history of asthma and some aspects of the practice of allergology in the tropics. Theoretically it can also influence the epidemiological trends of allergic diseases either by its absence or presence in different regions and countries.

Hygienic conditions influence sensitization to Blomia tropicalis allergenic components: Results from the FRAAT birth cohort.

BACKGROUND: In tropical zones, perennial exposure to house dust mite (HDM) allergens and helminth infections is present. Studying the impact of these conditions on the inception and evolution of allergic diseases is necessary to have an accurate view of their natural history. We aimed to evaluate the dynamics of genuine sensitization to Blomia tropicalis and Ascaris in children from the FRAAT birth cohort and the effects of helminth infection, environmental HDM allergen levels, and sociodemographic factors. METHODS: Children were followed up to 6 years old. Specific IgE to recombinant allergens from B. tropicalis (Blo t 5 and Blo t 12) and Ascaris spp (Asc l 3, Asc l 13 and Asc s 1) was measured by ELISA at different time points. Allergen levels were measured in dust when children were 6 months old. RESULTS: IgE sensitization increased over time up to 3 years old. Correlation among the specific IgE levels to B. tropicalis and Ascaris components is poor at year 1, but coefficients are high and significant (Spearman's rho coefficients >0.70) at year 6. Unhygienic conditions increased the odds of sensitization to B. tropicalis allergenic components. Blo t 5 levels were lower in the poorest. IgE response to Blo t 5 and Blo t 12 was less intense in children with high exposure to Blo t 5 (levels >80th percentile). CONCLUSION: In this tropical community, the pattern of childhood IgE sensitization is different from that in developing countries and is influenced by the hygienic conditions.

Frequency of Toxocara spp. antibodies in umbilical cords of newborns attended atthe University Hospital in Southern Brazil and factors associated with infection.

Toxocariasis is a neglected and geographically widespread parasitic disease. The detection of specific antibodies associated with this disease is required to confirm its clinical diagnosis and to aid in prevention. Although helminth infection during pregnancy can promote foetal immune responses with long-term effects, specific information regarding the risk of Toxocara spp. infection to the human foetus during pregnancy is lacking. Therefore, the present study aimed to investigate the frequency of antibodies against Toxocara spp. in umbilical cord serum samples to determine the neonatal risk factors associated with Toxocara spp. infection. A cross-sectional study of the frequency of specific antibodies against Toxocara spp. was performed on umbilical cord samples of 280 neonates. A cord blood sample was obtained from each newborn after parturition, and serum samples were examined by enzyme-linked immunoassay. Epidemiological data were obtained through a questionnaire regarding obstetric history (abortion history, premature birthhistory, and pregnancy and birth numbers), general aspects (animal contact anddiet) and socio-economic factors. The frequency of anti-Toxocara spp. IgG antibodies in the umbilical cords of neonates was 20% in serum pre-adsorbed with Ascaris spp. antigen. Family income and dog ownership were considered risk factors associated with infection. No association was found between reproductive disorders and Toxocara seropositivity. The 20% frequency rate of anti-Toxocara spp. IgG antibodies in sera from umbilical cords of newborns can be related to IgG binding at the maternal-foetal interface, requiring greater care during pregnancy. Anti-Toxocara IgM and IgE antibodies no were found in umbilical cord serum samples, indicating that no vertical transmission of these parasites occurred in this population. Studies regarding antibodies against Toxocara spp. in umbilical cord sera are important for determining neonatal exposure to these parasites.

Concomitant helminth infection downmodulates the Vaccinia virus-specific immune response and potentiates virus-associated pathology.

The aim of this work was to elucidate the immunopathological mechanisms of how helminths may influence the course of a viral infection, using a murine model. Severe virulence, a relevant increase in the virus titres in the lung and a higher mortality rate were observed in Ascaris and Vaccinia virus (VACV) co-infected mice, compared with VACV mono-infected mice. Immunopathological analysis suggested that the ablation of CD8+ T cells, the marked reduction of circulating CD4+ T cells producing IFN-γ, and the robust pulmonary inflammation were associated with the increase of morbidity/mortality in co-infection and subsequently with the negative impact of concomitant pulmonary ascariasis and respiratory VACV infection for the host. On the other hand, when evaluating the impact of the co-infection on the parasitic burden, co-infected mice presented a marked decrease in the total number of migrating Ascaris lung-stage larvae in comparison with Ascaris mono-infection. Taken together, our major findings suggest that Ascaris and VACV co-infection may potentiate the virus-associated pathology by the downmodulation of the VACV-specific immune response. Moreover, this study provides new evidence of how helminth parasites may influence the course of a coincident viral infection.

IgE responses to Ascaris and mite tropomyosins are risk factors for asthma.

BACKGROUND: The relationship between helminthiases and allergy is a matter of considerable interest and research. In the tropics, house dust mite exposure, a known risk factor for asthma, is frequently concurrent with helminth infections. It remains to be defined whether infection with the common roundworm Ascaris or its bystander immunological effects influence the prevalence and pathogenesis of asthma independently of mite sensitization. OBJECTIVE: To investigate the relationship between the IgE responses to Ascaris and its purified allergens and the risk of asthma in a tropical country. METHODS: A nested case-control study was performed in 356 subjects who reported current and past asthma symptoms (asthmatics) and 435 controls that had never experienced such symptoms. They were tested for serum levels of total IgE and specific IgE to Ascaris extract, Asc s 1 (ABA-1), Asc l 3 (tropomyosin) and GST (glutathione transferase). In addition, specific IgE to Dermatophagoides pteronyssinus, Blomia tropicalis and their tropomyosins Der p 10 and Blo t 10 was measured. Sensitization was defined as a positive specific IgE result to any extract or recombinant allergen. RESULTS: Sensitization to Ascaris and D. pteronyssinus was independently associated with asthma after adjustment for age, gender, socio-economic stratum, city and other IgE levels (adjusted ORs: 2.17; 95% CI 1.37-3.42 and 2.46; 95% CI 1.54-3.92), respectively. There was also a significant association with sensitization to the highly allergenic and cross-reactive tropomyosins Asc l 3, Blo t 10 and Der p10 (aORs: 1.76; 95% CI 1.21-2.57, 1.64; 95% CI 1.14-2.35 and 1.51; 95% CI 1.02-2.24), respectively. CONCLUSION AND CLINICAL RELEVANCE: IgE responses to Ascaris are associated with asthma symptoms in a population living in the tropics. Sensitization to the cross-reactive Ascaris and mite tropomyosins partially underlies this finding. These results have potential relevance in asthma diagnosis and management.

Early life IgE responses in children living in the tropics: a prospective analysis.

BACKGROUND: There are few birth cohort studies analyzing IgE sensitization in the tropics. OBJECTIVES: We aimed to describe the evolution of total IgE and specific IgE responses to house-dust mite (HDM) allergens and Ascaris in a birth cohort (Risk Factors for Asthma and Allergy in the Tropics, FRAAT), analyzing their relationships with wheezing. METHODS: Total and specific IgE were measured by ImmunoCap in mothers and children at four different time points (S1-S4) between 0 and 42 months. Parasite infection was evaluated by stool examination. RESULTS: Maternal total IgE (aOR: 2.43, 95% CI: 1.09-5.43; p = 0.03) and socio-demographic factors were associated with high cord blood (CB) total IgE. High CB total IgE was positively associated with higher Blomia tropicalis and Ascaris-specific IgE values during lifetime, but protected from recurrent wheezing (aOR: 0.26, 95% CI: 0.08-0.88, p = 0.03). Prevalence rates of IgE sensitization were high; at around 3 yr old, they were 33.3, 18.6, and 26.5% for B. tropicalis, Dermatophagoides pteronyssinus, and Ascaris, respectively. Indicators of unhygienic conditions were risk factors for HDM and Ascaris sensitization in children. A weak statistical association between B. tropicalis-specific IgE and ever wheezing was found (aOR: 1.47 95% CI: 1.00-2.28, p = 0.05). CONCLUSIONS: In a socioeconomically deprived community from the tropics, sensitization to HDM allergens was very frequent at early life, especially to B. tropicalis. In contrast to expected according to the hygiene hypothesis, unhygienic/poverty conditions were risk factors for allergen sensitization. High CB total IgE levels were a risk factor for allergen sensitization but protected from recurrent wheezing.

A cross-reactive monoclonal antibody to nematode haemoglobin enhances protective immune responses to Nippostrongylus brasiliensis.

BACKGROUND: Nematode secreted haemoglobins have unusually high affinity for oxygen and possess nitric oxide deoxygenase, and catalase activity thought to be important in protection against host immune responses to infection. In this study, we generated a monoclonal antibody (48Eg) against haemoglobin of the nematode Anisakis pegreffii, and aimed to characterize cross-reactivity of 4E8g against haemoglobins of different nematodes and its potential to mediate protective immunity against a murine hookworm infection. METHODOLOGY/PRINCIPAL FINDINGS: Immunoprecipitation was used to isolate the 4E8g-binding antigen in Anisakis and Ascaris extracts, which were identified as haemoglobins by peptide mass fingerprinting and MS/MS. Immunological cross-reactivity was also demonstrated with haemoglobin of the rodent hookworm N. brasiliensis. Immunogenicity of nematode haemoglobin in mice and humans was tested by immunoblotting. Anisakis haemoglobin was recognized by IgG and IgE antibodies of Anisakis-infected mice, while Ascaris haemoglobin was recognized by IgG but not IgE antibodies in mouse and human sera. Sequencing of Anisakis haemoglobin revealed high similarity to haemoglobin of a related marine nematode, Psuedoterranova decipiens, which lacks the four -HKEE repeats of Ascaris haemoglobin important in octamer assembly. The localization of haemoglobin in the different parasites was examined by immunohistochemistry and associated with the excretory-secretary ducts in Anisakis, Ascaris and N. brasiliensis. Anisakis haemoglobin was strongly expressed in the L3 stage, unlike Ascaris haemoglobin, which is reportedly mainly expressed in adult worms. Passive immunization of mice with 4E8g prior to infection with N. brasiliensis enhanced protective Th2 immunity and led to a significant decrease in worm burdens. CONCLUSION: The monoclonal antibody 4E8g targets haemoglobin in broadly equivalent anatomical locations in parasitic nematodes and enhances host immunity to a hookworm infection.

Blomia tropicalis Blo t 5 and Blo t 21 recombinant allergens might confer higher specificity to serodiagnostic assays than whole mite extract.

BACKGROUND: Blomia tropicalis is a dust mite and an important source of allergens in tropical regions. Up to now, the assays to diagnose atopy to this mite use whole body extract as antigens. However, anti-B. tropicalis IgE antibodies cross-react with Ascaris lumbricoides antigens, hindering the diagnosis of allergy to this mite. In this study, B. tropicalis recombinant allergens were evaluated with the purpose of developing an immunodiagnostic assay for allergy to this mite with greater specificity than those commercially available. METHODS: Two B. tropicalis allergens (Blo t 5 and Blo t 21) were cloned into a plasmidial expression vector, expressed in Escherichia coli and purified by affinity chromatography. Sixty-three sera containing anti-B. tropicalis extract (BtE) IgE antibodies were used to investigate IgE reactivity to the recombinant Blot 5 and 21 allergens. Inhibition assays with 20 sera pre-adsorbed with A. lumbricoides extract were performed using rBlo t 5, rBlo t 21, and BtE as antigens. All the assays were carried using indirect ELISA. RESULTS: Eighty-two point nine percent and 80.0% of the sera with anti-BtE antibodies from 35 children reacted with rBlo t 5 and rBlo t 21, respectively, whereas 92.8% and 89.3% of the 28 sera with anti-BtE antibodies from adult asthma patients reacted with the same allergens, and 96.4% of these sera reacted with a mixture of rBlo t 5 and rBlo t 21. In an inhibition ELISA, the absorption of sera by A. lumbricoides extract affected less the reaction with rBlo t 5 and rBlo t 21 than with BtE. CONCLUSIONS: The rBlo t 5 and rBlo t 21 allergens contain important epitopes recognized by IgE antibodies of individuals allergic to B. tropicalis antigens. Moreover, the assays using the recombinant allergens had lower IgE cross-reactivity with A. lumbricoides antigens, a fact which would confers higher specificity to serodiagnostic assays than the crude mite extract. However, additional recombinant allergens should be evaluated in order to reach the same sensitivity of the commercially available assays based on mite extract.

Effects of geohelminth infection and age on the associations between allergen-specific IgE, skin test reactivity and wheeze: a case-control study.

BACKGROUND: Most childhood asthma in poor populations in Latin America is not associated with aeroallergen sensitization, an observation that could be explained by the attenuation of atopy by chronic helminth infections or effects of age. OBJECTIVE: To explore the effects of geohelminth infections and age on atopy, wheeze, and the association between atopy and wheeze. METHODS: A case-control study was done in 376 subjects (149 cases and 227 controls) aged 7-19 years living in rural communities in Ecuador. Wheeze cases, identified from a large cross-sectional survey, had recent wheeze and controls were a random sample of those without wheeze. Atopy was measured by the presence of allergen-specific IgE (asIgE) and skin prick test (SPT) responses to house dust mite and cockroach. Geohelminth infections were measured in stools and anti-Ascaris IgE in plasma. RESULTS: The fraction of recent wheeze attributable to anti-Ascaris IgE was 45.9%, while those for SPT and asIgE were 10.0% and 10.5% respectively. The association between atopy and wheeze was greater in adolescents than children. Although Anti-Ascaris IgE was strongly associated with wheeze (adj. OR 2.24 (95% CI 1.33-3.78, P = 0.003) and with asIgE (adj. OR 5.34, 95% CI 2.49-11.45, P < 0.001), the association with wheeze was independent of asIgE. There was some evidence that the association between atopy and wheeze was greater in uninfected subjects compared with those with active geohelminth infections. CONCLUSIONS AND CLINICAL RELEVANCE: Atopy to house dust mite and cockroach explained few wheeze cases in our study population, while the presence of anti-Ascaris IgE was an important risk factor. Our data provided only limited evidence that active geohelminth infections attenuated the association between atopy and wheeze in endemic areas or that age modified this association. The role of allergic sensitization to Ascaris in the development of wheeze, independent of atopy, requires further investigation.

Allergy in the tropics: the impact of cross-reactivity between mites and ascaris.

Allergic diseases and nematode infections such as ascariasis are important health problems in underdeveloped tropical countries. The co-exposure to Ascaris lumbricoides and the domestic mites Blomia tropicalis and Dermatophagoides pteronyssinus induces a strong Th2 and immunomodulatory responses that can modify the natural history of both diseases. An associate phenomenon of these particular environmental conditions is cross reactivity between mite and Ascaris allergens. We demonstrated a high IgE cross reactivity between the allergenic extracts from both sources and that several already known allergens like tropomyosin and glutathione-s-tranferases are involved. Although this cross reactive antibody response has not been completely analyzed, there are clinical and experimental evidences suggesting that it could be an important component of the complex interactions between ascariasis and mite allergy. For example, it may affect the specificity of serological IgE tests for diagnosing both ascariasis and allergic diseases and, in consequence, the results of epidemiological surveys evaluating the predisposing or protecting role of ascariasis on allergy. In this review we discuss the potential role of cross reactivity on several aspects of allergy in the tropics that have been the matter of a number of investigations, some of them with controversial results.

IgE cross-reactivity between Ascaris and domestic mite allergens: the role of tropomyosin and the nematode polyprotein ABA-1.

BACKGROUND: Analysis of cross-reactivity between the nematode Ascaris ssp. and dust mites, two important allergen sources in the tropics, will contribute in understanding their influence on asthma and atopy. The objective of this study was to investigate immunoglobulin E (IgE) cross-reactivity between Ascaris and two domestic mites in the tropics. METHODS: Sera from 24 asthmatic patients were used in ELISA and immunoblotting IgE-binding inhibition assays using Ascaris, Blomia tropicalis and Dermatophagoides pteronyssinus extracts and the recombinants Blo t 10, ABA-1 and Blo t 13 as competitors. Identification of Ascaris allergens was confirmed by mass spectrometry (LC-MS/MS). RESULTS: We detected at least 12 human IgE-binding components in Ascaris extract. Blomia tropicalis and D. pteronyssinus inhibited 83.3% and 79% of IgE-binding to Ascaris, while Ascaris inhibited 58.3% and 79.3% to B. tropicalis and D. pteronyssinus respectively. Mite tropomyosin inhibited 85% of IgE-binding to Ascaris. Affinity-purified human IgE to rBlo t 10 identified an allergen of 40 kDa in Ascaris extract, further confirmed as tropomyosin by LC-MS/MS. We found no evidence of IgE cross-reactivity between rABA-1 and any allergen component in mite extracts, including rBlo t 13. CONCLUSIONS: There is cross-reactivity between Ascaris and mites, determined by several allergens including tropomyosin and glutathione-S-transferase. In addition to its potential impact on asthma pathogenesis, Ascaris infection and mite allergy diagnosis relying on the determination of specific IgE could be affected by this cross-reactivity. ABA-1 has no cross-reactive counterpart in mite extracts, suggesting its usefulness as a more specific marker of Ascaris infection.

Atopic phenotype is an important determinant of immunoglobulin E-mediated inflammation and expression of T helper cell type 2 cytokines to ascaris antigens in children exposed to ascariasis.

Studies have shown a strong inverse relationship between atopy and geohelminth infection, indicating that atopy may protect against geohelminth infection. Resistance to ascariasis in atopic individuals may occur through greater immunoglobulin E-mediated responses and expression of T helper cell type 2 (Th2) cytokines to parasite antigens. To investigate the effect that atopy has on the immune response to Ascaris antigens, school-age children were recruited from rural schools in Ecuador. Immunologic variables were compared between children stratified by atopic and/or A. lumbricoides-infection status; the variables included cytokine expression by peripheral-blood mononuclear cells (PBMCs) and histamine release in response to Ascaris antigens. Atopic children had both greater frequencies of PBMCs expressing interleukin (IL)-4 and IL-5 and enhanced histamine release, compared with those in nonatopic children. Stratification by atopic and A. lumbricoides-infection status revealed the greatest histamine and Th2 cytokine responses in the stratum of atopic, noninfected children. Multivariate regression analyses showed significant effects for atopic status but not for infection status on Th2 cytokine expression and histamine release.

Atopy, asthma, and antibodies to Ascaris among rural and urban children in Kenya.

OBJECTIVE: The purpose of this study was to evaluate differences in the relationship between asthma and immune responses to allergens in children living in rural and urban areas of Kenya. STUDY DESIGN: Children (mean age, 11 years) from Kabati (n = 136), a rural village, and Thika (n = 129), a small town, were studied by skin testing and serum immunoglobulin E (IgE) and immunoglobulin G (IgG) antibody measurement. Asthma was evaluated by symptoms, as well as spirometry before and after vigorous exercise to test for exercised-induced bronchospasm (EIB). School children from a study performed in Atlanta, Georgia, were used for comparison of anthropometric and immunologic results. RESULTS: Compared with the urban area of Kenya, children living in the rural area had a lower percentage of body fat, smaller and fewer skin test responses to allergens, a higher prevalence of IgE antibodies to Ascaris (67% vs 26%) and 10-fold higher total IgE. In the urban area of Kenya, there was a strong correlation between EIB and atopy determined both by IgE antibodies (P =.02) and skin tests (P =.002). By contrast, in the rural area, none of the 13 children with EIB were skin-test positive (vs 13/109 of children without EIB). CONCLUSIONS: Among the rural children, there was no association between immune responses to allergens and airway-related symptoms or reactivity. The association between asthma and atopy seen in the town of Thika may represent an important step in the increase in asthma seen both in urban Africa and in the West.

Genetic variation in sympatric Ascaris populations from humans and pigs in China.

It has recently been shown using genetic markers that Ascaris in humans and pigs in Central America comprise reproductively isolated populations. We present a similar analysis for a region of China in which close association between pigs and humans has been the norm for thousands of years, and agricultural practices will result in frequent exposure to eggs from both sources. DNA fragments from selected regions of mitochondrial and ribosomal DNA were amplified by PCR and allelic forms identified following digestion with a panel of restriction enzymes, using DNA from a total of 115 individual worms from both people and pigs from 2 neighbouring villages. Significant frequency differences in both mtDNA haplotypes and the rDNA spacer were found between the 2 host-associated populations, indicating that they represented reproductively isolated populations. Mitochondrial haplotype frequencies were different from those observed in Guatemala and also from other Asian Ascaris populations, suggesting low levels of gene flow between populations. However, we found no evidence for significant heterogeneity in the genetic composition of Ascaris infrapopulations in either humans or pigs, possibly indicative of agricultural practices in China which have resulted in a random distribution of alleles within the parasite populations.

Ascaris reinfection of slum children: relation with the IgE response.

Total and Ascaris-specific serum IgE levels were measured in a group of 98 Ascaris-infected children from a slum area of Caracas, Venezuela, in whom the infections were eliminated by regular treatment for 22 months with the anthelmint Oxantel/Pyrantel ('Quantrel'). The children were re-evaluated at the end of the treatment programme, and then 8 months later, at which time reinfection was assessed. Total IgE levels at the beginning of the study were significantly higher in the children who became reinfected after treatment, compared with those who did not. The anthelmint treatment caused a significant decrease in the total IgE levels in most of the children, and after a period of 8 months without treatment these continued to decrease in the non-reinfected group, but increased again in the reinfected children. The reverse pattern was found for Ascaris-specific IgE antibody levels, and in fact an inverse correlation was found between total and anti-Ascaris IgE levels. Striking associations were found between reinfection and high pretreatment values of total IgE, but low levels of specific IgE antibody. These data support the concept that specific IgE antibody may participate in the protection against helminthic infection, and suggest that the polyclonal stimulation of IgE synthesis caused by these parasites may reduce the effectiveness of such responses. The results also indicate that different individuals have varying propensities to respond polyclonally to the helminths, and this influences their resistance to infection.

Modulation of the allergic reactivity of slum children by helminthic infection.

Infection by helminthic parasites can cause the polyclonal stimulation of IgE synthesis, possibly via an enhanced production of interleukin-4 (IL-4), and this has been suggested to influence the allergic reactivity of tropical populations where these parasites are endemic. We evaluated a group of urban slum children in Caracas, Venezuela, with a high prevalence of helminthic infection (70.8%), to establish the relationship between the elevated IgE levels (3696 IU/ml) induced by these parasites and various aspects of the allergic response. Although the absolute levels of IL-4 detected in the sera of these children were low (0.65 +/- 0.20 ng/ml), a strong positive correlation (r = 0.78) was found between these and serum IgE. The cutaneous immediate hypersensitivity reactivity to extracts of common environmental allergens was relatively low (17.5% to house dust), although that to Ascaris extract was moderately high (49.4%). Significant inverse correlations were found between total IgE levels and the different skin test reaction diameters, including Ascaris. The positivity of Prausnitz-Kustner passive transfer tests was low in this group (34%), with a strong inverse correlation (r = -0.75) being found between this and total IgE levels. Significant inverse correlations were also found between total IgE levels and specific IgE antibody to environmental allergens, and to Ascaris antigen. We suggest that the polyclonal production of IgE stimulated by helminthic infection can suppress the allergic response to environmental and parasite allergens via both mast cell saturation and inhibition of specific IgE production.

Suppression of the IgE antibody response by Ascaris suum components: effect of X-irradiation.

The effect of X-irradiation on the suppression of IgE antibody responses induced by some of the Ascaris suum (ASC) components was analyzed in mice (7-week old A/Sn females). Treatment with 300 R 24 h before immunization with 50 micrograms OVA and 200 micrograms ASC suppressive components abolished the damping effect on anti-OVA IgE antibody levels. The same effect was observed on the anti-ASC IgE antibody response obtained in mice injected with 200 micrograms ASC immunogenic plus 200 micrograms ASC suppressive components. Moreover, the failure of suppressive components to induce an IgE anti-ASC antibody response on their own was also abolished by X-irradiation. These results indicate that the suppressive components are able to elicit an IgE antibody response, but simultaneously activate a regulatory mechanism which suppresses both the homologous (anti-ASC) and heterologous (anti-OVA) antibody formation.