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In allergen immunotherapy, beneficial responses have been associated with high IgG4\/IgE ratios. Helminths potentiate antibody class switching to IgG4 and stimulate polyclonal IgE synthesis; therefore, we hypothesized a role for helminth\u2010associated IgG4 and total IgE in protection against atopic sensitization and clinical allergy (asthma) in tropical low\u2010income countries.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Among community residents of Ugandan rural <jats:italic>Schistosoma mansoni<\/jats:italic> (<jats:italic>Sm<\/jats:italic>)\u2013endemic islands and a mainland urban setting with lower helminth exposure, and among urban asthmatic schoolchildren and non\u2010asthmatic controls, we measured total, <jats:italic>Schistosoma<\/jats:italic> adult worm antigen (SWA)\u2013specific, <jats:italic>Schistosoma<\/jats:italic> egg antigen (SEA)\u2013specific and allergen (house dust mite [HDM] and German cockroach)\u2013specific IgE and IgG4 by ImmunoCAP<jats:sup>\u00ae<\/jats:sup> and\/or ELISA. We assessed associations between these antibody profiles and current <jats:italic>Sm<\/jats:italic> infection, the rural\u2010urban environment, HDM and cockroach skin prick test (SPT) reactivity, and asthma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Total IgE, total IgG4 and SWA\u2010, SEA\u2010 and allergen\u2010specific IgE and IgG4 levels were significantly higher in the rural, compared to the urban setting. In both community settings, both <jats:italic>Sm<\/jats:italic> infection and SPT reactivity were positively associated with allergen\u2010specific and total IgE responses. SPT reactivity was inversely associated with <jats:italic>Schistosoma<\/jats:italic>\u2010specific IgG4, allergen\u2010specific IgG4\/IgE ratios and total IgE\/allergen\u2010specific IgE ratios. Asthmatic schoolchildren, compared with non\u2010asthmatic controls, had significantly higher levels of total and allergen\u2010specific IgE, but lower ratios of allergen\u2010specific IgG4\/IgE and total IgE\/allergen\u2010specific IgE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and clinical relevance<\/jats:title><jats:p>Our immuno\u2010epidemiological data support the hypothesis that the IgG4\u2013IgE balance and the total IgE\u2013allergen\u2010specific IgE balance are more important than absolute total, helminth\u2010 or allergen\u2010specific antibody levels in inhibition of allergies in the tropics.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cea.13834","type":"journal-article","created":{"date-parts":[[2021,1,29]],"date-time":"2021-01-29T13:12:07Z","timestamp":1611925927000},"page":"703-715","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Allergen skin test reactivity and asthma are inversely associated with ratios of IgG4\/IgE and total IgE\/allergen\u2010specific IgE in Ugandan communities"],"prefix":"10.1111","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4062-9105","authenticated-orcid":false,"given":"Gyaviira","family":"Nkurunungi","sequence":"first","affiliation":[{"name":"Immunomodulation and Vaccines Programme Medical Research Council \/ Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine (MRC\/UVRI and LSHTM) Uganda Research Unit Entebbe Uganda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacent","family":"Nassuuna","sequence":"additional","affiliation":[{"name":"Immunomodulation and Vaccines Programme Medical Research Council \/ Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine (MRC\/UVRI and LSHTM) Uganda Research Unit Entebbe 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