Specific pattern of flea antigen recognition by IgG subclass and IgE during the progression of papular urticaria caused by flea bite

doi:10.1016/j.aller.2009.09.012

Allergologia et Immunopathologia

Volume 38, Issue 4, July–August 2010, Pages 197-202

https://doi.org/10.1016/j.aller.2009.09.012 Get rights and content

Abstract

Background

Papular urticaria caused by flea bite presents clinical symptoms of a hypersensitivity reaction accompanied by skin lesions. However, the pattern of recognition by different antibody isotypes during the progression of the disease is unknown. This study evaluated variations in immunoglobulin E and immunoglobulin G subclass antibody responses to flea antigens during the progression of papular urticaria caused by flea bite

Methods

Twenty-five patients clinically diagnosed with papular urticaria due to flea bite were included. Ten healthy children were included as controls. Recognition of antigens from complete flea body extract by patients and healthy controls was determined using immunoblot assays.

Results

The results revealed that patients with 2–5 years of papular urticaria evidenced more IgE bands than those with shorter or longer durations of symptoms. In contrast, healthy children showed a predominance of immunoglobulin G1 and immunoglobulin G3. The majority of the recognised antigens were low molecular weight proteins (<90 kDa). Proteins with molecular weights between 16–20, 21–25, and 31–35 kDa showed different patterns of recognition between patients and healthy children.

Conclusion

The predominant specific antibody isotypes vary according to the time elapsed since the onset of symptoms in papular urticaria caused by flea bite.

Introduction

Papular urticaria is a pathology caused by the bite of insects such as mosquitoes, bedbugs, flies and fleas, among others.

Papular urticaria caused by flea bite (PUFB) is a hypersensitivity reaction characterised by groups or clusters of papules, frequently associated with grouped itchy papules. The papules are often accompanied by intermittent and chronic excoriation that results in hypo- or hyper-pigmented macules, severe infections, and scars. The pathophysiology of papular urticaria remains to be fully elucidated. The presence of eosinophils, the predominance of CD4 T lymphocytes, and the observed immunoglobulin (Ig) E and IgG response patterns indicate that the immune reaction to flea antigens in human patients may occur through more than one mechanism.¹

The role of antibodies has been demonstrated in the development of allergic inflammation mediated by IgE and IgG subclasses, by activating mast cells and the formation of immune complexes.

Regarding the humoral immune response associated with PUFB, canine models have shown that dogs with hypersensitivity to flea bites have higher levels of specific IgE and IgG antibodies to flea antigens than dogs that have never been bitten by fleas.² Additionally, a human study demonstrated IgE and IgG recognition of flea extract proteins within a range of 26–150 kilodaltons (kDa). However, in this study, recognition of flea proteins by IgE tends to decrease with disease progression.¹

In papular urticaria by mosquito bite, elevated mosquito saliva serum-specific IgE has been detected in mosquito-allergic or mosquito bite test positive subjects. The time frame of the immediate reaction to mosquito bites is compatible with that of IgE-mediated type I hypersensitivity. Mosquito bite-induced immediate wheals and flares correlate well with mosquito salivary gland-specific IgE levels. The development of skin sensitisation to mosquito bites also parallels the levels of saliva specific IgE antibodies. In individuals with systemic reactions, saliva-specific IgE levels are significantly increased. Mosquito saliva-specific IgG antibodies, consisting mainly of the IgG4 and IgG1 subclasses, have been found to be significantly elevated in individuals with positive mosquito bite tests and in individuals with severe local reactions, but not systemic reactions, to mosquito bites. Levels of mosquito saliva-specific IgG correlate with the sizes of both immediate and delayed skin reactions and with saliva-specific IgE levels.³

To date, it is not clear whether there is a differential isotype pattern associated with PUFB. The aim of the present study was to identify variations in IgE and IgG subclass-mediated responses to flea antigens during the progression of PUFB.

Section snippets

Study population

The sample included 25 patients, aged 1 to 15 years, who were clinically diagnosed with PUFB. They were attended to by the Pediatric Dermatology and Allergy division of the Fundación Santa Fe de Bogotá, in Bogotá, Colombia. Patients excluded from consideration for participation in the study included those with secondary infected lesions, immuno-suppression due to systemic disease, treatment with immuno-suppressive medication five days before the consultation, and/or treatment with flea extract.

Results

In agreement with our previous studies, in which we find differences in the answer of antibodies IgE and IgG against the flea antigens,¹ the patients were subdivided into three groups according to the time elapsed from the initial onset of symptoms: group 1 (2 years since the onset of symptoms, n=10 patients); group 2 (2–5 years since the onset of symptoms, n=10 patients); and group 3 (more than 5 years since the onset of symptoms, n=5 patients). Among all patients included in the study, 28% of

Discussion

The immune response associated with papular urticaria in humans and caused by ectoparasite bites has been mostly studied for mosquitoes.³ Some reports in adult patients with histories of systemic allergic reactions to mosquito bites showed higher levels of IgE antibodies against allergens of different mosquito species compared to healthy adults, although no difference was observed regarding IgG levels.⁵ When assessing the antibody response in allergic individuals, an increase in IgE, IgG4, and

Acknowledgments

The authors wish to thank the collaboration of doctors Manuel Forero, Mariela Tavera, Clara Ordoñez, Ana María Salazar, and Adriana Motta for help to get the patients, and Claudia Satizabal and Juliana Quintero, from Fundación Santa Fe de Bogotá, who contributed to the statistical analyses and edition of the document.

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Cited by (13)

Novel salivary gland allergens from tropical mosquito species and IgE reactivity in allergic patients
2020, World Allergy Organization Journal
Citation Excerpt :
Our case-control comparison has a limitation in that the average age of the control group is higher than the patients, due to ethical consideration and the lack of parental interest in allowing blood sample collections from healthy children. IgE recognition of insect allergens causing skin hypersensitivity, including those from mosquito, has been reported to decrease with age23,24 and this is in agreement with the acquisition of tolerance that characterizes this disease.3 Thus, IgE levels in adults and children may differ, and additional study with more age-matched controls is needed.
Mosquito allergy is common in tropical countries but remains under-diagnosed. This may be due to the lack of knowledge and diagnostic tools for tropical mosquito allergens.
We aimed to characterize allergens from tropical mosquito species and investigate IgE reactivity in mosquito-allergic patients to the salivary gland proteins from these mosquitoes.
Salivary gland extract (SGE) from 4 mosquito species, highly distributed in the tropics, including Aedes aegypti, Aedes albopictus, Culex quinquefasciatus, and Anopheles dirus b, were studied. SGE-specific IgE and IgG ELISA were developed, and serum from 64 mosquito-allergic and 22 non-allergic healthy control subjects was assayed. Further investigations using IgE-immunoblots followed by mass spectrometry analysis were performed to identify and characterize allergens from each species.
Mosquito-allergic subjects have detectable serum IgE to SGE derived from local mosquito species, while the IgE levels to Aedes communis using commercially available ELISA were mostly minimal. IgE-immunoblot analysis and mass spectrometry identified 5 novel mosquito allergens from A. albopictus (Aed al 2, Aed al 3), C. quinquefasciatus (Cul q 2.01, Cul q 3), and A. dirus b (Ano d 2). Interestingly, 4 of the 5 new allergens belong to the D7 protein family.
Five novel allergens from 3 tropical mosquito species were characterized. The majority of mosquito-allergic subjects who live in the tropics have IgE reactivity to these allergens. Our study paves the way for the development of diagnostic tests, component-resolved diagnostics, and future immunotherapy for mosquito allergy in tropical countries.
Prevalence of papular urticaria caused by flea bites and associated factors in children 1-6 years of age in Bogotá, D.C.
2017, World Allergy Organization Journal
Citation Excerpt :
These papules were most often located in areas where clothing fits snugly, such as under the socks and the waistband. In some patients, exposed areas of the body extremities were also affected [7, 17]. As a case, it was considered a patient diagnosed with FBPU by physical examination.
Background Papular urticaria is a chronic inflammatory disease caused by exposure to arthropod bites. The disease has been reported in children attending medical centers, but the causes as the risk factors associated with the disease have not been established. The objective of this study was to determine the prevalence of papular urticaria caused by flea bite and identify the risk factors in children between 1 to 6 years of age in Bogotá D.C, between March 2009 and June 2011.
Methods A cross-sectional, two-stage, clustered study using random probability sampling and stratified with proportional allocation was carried out in children (1–6 years of age) in educational institutions in Bogotá D.C. to determine the prevalence of the disease. Children underwent a dermatological examination by general practitioners with a previous training. Furthermore, digital photographs of skin lesions were taken for further confirmation of the diagnosis by dermatologists. A structured survey was completed by the parents or caregivers, and it was evaluated using an unconditional logistic regression to identify factors associated with the disease.
Results A total of 2437 children were included in the study. The prevalence of papular urticaria caused by flea bite in this population was 20.3% (CI 95%: 18.2 to 22.5%). The major risk factors associated with the disease were the presence of fleas in households (OR 1.74, CI 95%: 1.35 to 2.25), using mattresses without springs (OR 1.73, CI 95%: 1.20 to 2.50), the use of daily public transportation to carry the children to the educational institutions (OR 1.76, CI 95%: 1.07 to 2.89), having a soil/earth floor in the main bedroom (OR 6.81, CI 95%:1.16–39.96), and having siblings with a history of atopic dermatitis (OR 1.76 CI 95%: 1.07–2.89).
Conclusions A high prevalence of papular urticaria caused by flea bite was found in Bogotá D.C. The main factors associated with the disease might be modified with the implementation of prevention, control strategies in housing, educational institutions, and public transportation.
Particularities of allergy in the Tropics
2016, World Allergy Organization Journal
Citation Excerpt :
In addition, the humoral response profile changes in a time dependent manner. Patients having more than 5 years from the beginning of the symptoms show IgG3 reactivity rates which are similar to the control group, especially for proteins between 31 and 35 kDa [186]. There is an increasing interest in evaluating purified, mainly recombinant antigens and allergens involved in PU.
Allergic diseases are distributed worldwide and their risk factors and triggers vary according to geographical and socioeconomic conditions. Allergies are frequent in the Tropics but aspects of their prevalence, natural history, risk factors, sensitizers and triggers are not well defined and some are expected to be different from those in temperate zone countries. The aim of this review is to investigate if allergic diseases in the Tropics have particularities that deserve special attention for research and clinical practice. Such information will help to form a better understanding of the pathogenesis, diagnosis and management of allergic diseases in the Tropics. As expected, we found particularities in the Tropics that merit further study because they strongly affect the natural history of common allergic diseases; most of them related to climate conditions that favor permanent exposure to mite allergens, helminth infections and stinging insects. In addition, we detected several unmet needs in important areas which should be investigated and solved by collaborative efforts led by the emergent research groups on allergy from tropical countries.
Arthropods and diseases
2014, Medicine (Spain)
Los artrópodos son animales invertebrados que constituyen el Phylum más numeroso del reino animal. Desempeñan un papel importante en la patología humana actuando de dos formas diferentes: como vectores de otros agentes biológicos o como agentes causales directos de enfermedad. Los artrópodos pueden producir, en general, varios tipos de lesiones: lesiones traumáticas (las ocasionadas por crustáceos como cangrejos y langostas); reacciones anafilácticas (tras picaduras de abejas o avispas); lesiones directas (las producidas por los insectos del orden Anoplura [piojos], algunos coleópteros como los escarabajos o la mayor parte de los dípteros [Aedes, Anopheles, Culex, Culicoides]); lesiones tóxicas o inmunológicas, locales o sistémicas.
En general, será precisa la retirada del parásito causante en aquellos casos en los que se encuentre presente y tratar tanto los síntomas locales como los sistémicos.
Anthropods are invertebrate animals that constitute the most numerous Phylum of the animal kingdom. They play an important role in human pathology, acting in two different ways: as vectors of other biological agents or as direct causal agents of disease. In general, arthropods can produce several types of lesions: traumatic lesions (those caused by crustaceans as crab, lobster); anaphylactic reactions (after bee or wasp stings); direct lesions (those caused by insects of the Anoplura order [lice], some coleopteras as beetles or most of the dipteras [Aedes, Anopheles, Culex, Culicoides]); toxic or immunological, local or systemic lesions.
In general, it will be necessary to remove the causal parasite in those cases in which it is present and treat both the local and systemic symptoms.
Differences in IgE mediated basophil degranulation induced by proteic fractions from whole flea body extract in patients with papular urticaria by flea bite and healthy controls
2013, World Allergy Organization Journal
Citation Excerpt :
Proteins with molecular weights ranging 30 and 35 kDa were recognized by nearly 60% of patients. In addition, most of the recognized proteins by patients and controls, were those under 90 kDa [5]. Despite the advance in knowledge of the disease immuno-pathogenesis, at this moment diagnostic and treatment tools are not available for patient intervention.
Background Papular urticaria by flea bite (PUFB) is a chronic inflammatory disease in children. The aim of this study was to assess the functional activity of IgE to protein fractions from flea body extract, through basophil degranulation in PUFB patients and controls.
Methods Basophil degranulation, measured by overexpression of CD63 surface molecules, was evaluated by flow cytometry in samples from patients and controls. Cell stimulation was performed with three fractions with different molecular weight from flea body extract using a Basotest® modified protocol. Mann–Whitney U-test was used for comparisons.
Results Specific IgE from PUFB patients and healthy controls induced basophil degranulation to flea body extract with no significant differences between them (16.2 ± 3.1% vs 13.6 ± 2.8% p = 0.77). However, when flea extract was analyzed in fractions with proteins ranging different molecular weights, significant differences were observed on the response from patients compared with controls to <50 kD (14.9 ± 5.1% vs 9.7 ± 2.1% p = 0.0058) and 50–100 kD proteic fractions (8.3 ± 3.2% vs 2.8 ± 1.6% p = 0.0021).
Conclusion In this study, was established that the differential response by IgE, in PUFB, depends from the molecular weight of the antigens contained in the flea extract. These antigens may be related to 30–35 kD proteins previously described as major allergens.
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Original ArticleSpecific pattern of flea antigen recognition by IgG subclass and IgE during the progression of papular urticaria caused by flea bite

Abstract

Background

Methods

Results

Conclusion

Introduction

Section snippets

Study population

Results

Discussion

Acknowledgments

Ann Allergy Asthma Immunol

Vet. Immunol Immunopathol

J Allergy Clin Immunol

J Allergy Clin Immunol

Mol Immunol

Ann Allergy Asthma Immunol

Mosquito allergy: immune mechanisms and recombinant salivary allergens

Int Arch Allergy Immunol

Original Article
Specific pattern of flea antigen recognition by IgG subclass and IgE during the progression of papular urticaria caused by flea bite