Dissociation between skin test reactivity and anti-aeroallergen IgE: Determinants among urban Brazilian children

Abstract

BackgroundThe dissociation between specific IgE and skin prick test reactivity to aeroallergens, a common finding in populations living in low and middle-income countries, has important implications for the diagnosis and treatment of allergic diseases. Few studies have investigated the determinants of this dissociation. In the present study, we explored potential factors explaining this dissociation in children living in an urban area of Northeast Brazil, focusing in particular on factors associated with poor hygiene.MethodsOf 1445 children from low income communities, investigated for risk factors of allergies, we studied 481 with specific IgE antibodies to any of Blomia tropicalis, Dermatophagoides pteronyssinus, Periplaneta americana and Blatella germanica allergens. Data on demographic, environmental and social exposures were collected by questionnaire; serum IgG and stool examinations were done to detect current or past infections with viral, bacterial, protozoan and intestinal helminth pathogens. We measured atopy by skin prick testing (SPT) and specific IgE (sIgE) to aerollergens in serum (by ImmunoCAP). SIgE reactivity to B. tropicalis extract depleted of carbohydrates was measured by an in-house ELISA. Total IgE was measured by in house capture ELISA. SNPs were typed using Illumina Omni 2.5.ResultsNegative skin prick tests in the presence of specific IgE antibodies were frequent. Factors independently associated with a reduced frequency of positive skin prick tests were large number of siblings, the presence of IgG to herpes simplex virus, Ascaris lumbricoides and Trichuris trichiura infections, living in neighborhoods with infrequent garbage collection, presence of rodents and cats in the household and sIgE reactivity to glycosylated B. tropicalis allergens. Also, SNP on IGHE (rs61737468) was negatively associated with SPT reactivity.ConclusionsA variety of factors were found to be associated with decreased frequency of SPT such as unhygienic living conditions, infections, total IgE, IgE response to glycosylated allergens and genetic polymorphisms, indicating that multiple mechanisms may be involved. Our data, showing that exposures to an unhygienic environment and childhood infections modulate immediate allergen skin test reactivity, provide support for the “hygiene hypothesis”.

Parasites and allergy: Observations from Brazil

“…In the SCAALA study population, Toxocara seropositivity appeared to be a strong effect modifier of the association between anti‐aeroallergen‐IgE and that may, in part, explain the dissociation between the two markers of atopy (SPT and IgE) . Similar effect modification has been observed for infections with A. lumbricoides and T. trichiura in the same population . A possible explanation for such effect modification by helminth infections might be the presence of low‐affinity antibodies to helminths that cross‐react with arthropod allergens .…”

“…We also observed, in the same study population in Salvador, a marked dissociation between levels of allergen‐specific IgE and SPT to the same allergen such that many more children had detectable levels of specific IgE compared to SPT . There are several explanations for this dissociation such as competition between polyclonal and specific IgE for binding to high‐affinity receptors on mast cells and host genetic factors, among others. Additional studies are required to identify the mechanisms underlying this association …”

“…32 Similar effect modification has been observed for infections with A. lumbricoides and T. trichiura in the same population. 62 A possible explanation for such effect modification by helminth infections might be the presence of low-affinity antibodies to helminths that cross-react with arthropod allergens. 58,59 Such low-affinity IgE might have limited biological activity (ie, for the activation of mast cells).…”

Trickle infection and immunity to Trichuris muris

“…There is conflicting data as to the influence of chronic helminth/GI nematode infection upon the incidence of allergic responses e.g. skin prick tests in humans [52]. With regards to model systems studies using chronic H .…”

Trickle infection and immunity toTrichuris muris

“…There is conflicting data as to the influence of chronic helminth/GI nematode infection upon the incidence of allergic responses e.g. skin prick tests in humans (52). With regards to model systems studies using chronic H. polygyrus infections have shown that allergic lung responses are muted compared to non-infected animals (53, 54) and single low dose chronic infections with T. muris also influence lung allergic responsiveness (55).…”