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Does Parasitic Infection Protect Against Allergy? a Infecção Parasitária Protege Contra a Alergia?

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Does Parasitic Infection Protect Against Allergy? a Infecção Parasitária Protege Contra a Alergia? 0021-7557/06/82-04/241 Jornal de Pediatria Copyright © 2006 by Sociedade Brasileira de Pediatria doi:00.0000/JPED.0000 EDITORIAIS Does parasitic infection protect against allergy? A infecção parasitária protege contra a alergia? Ricardo U. Sorensen1, Pierre Sakali2 A imunoglobulina E (IgE) tem um papel central na crônica, em doenças de imunodeficiência que afetam os patogênese das reações de hipersensibilidade imediata linfócitos T reguladores, na rara síndrome hiper-IgE, com devido a sua capacidade de se ligar especificamente a infecções recorrentes, e em algumas doenças parasitárias. receptores IgE de alta afinidade em mastócitos ou basófilos Nas infecções parasitárias, o aumento das concentra- pela cadeia alfa do receptor FC épsilon tipo I (Fc-épsilon ções de IgE ocorre durante as fases metazoárias, com α 1 RI- ) . Além de sua capacidade de ativar mastócitos e aparente associação entre níveis crescentes de invasão do basófilos, a IgE pode se ligar ao receptor IgE de baixa tecido e níveis crescentes de IgE. Os parasitas mais comuns afinidade (CD23, ou Fc-épsilon RII) nas células B para associados com o aumento dos níveis de IgE incluem a larva ampliar as respostas imunes celulares migrans visceral (Toxocara canis), ca- 2 e humorais na doença alérgica . pilaríase intestinal (Capillaria philippi- A presença de concentrações de nensis), esquistossomose, ancilosto- IgE de altas a moderadas tem sido Veja artigo relacionado míase e equinococose. associada a doença alérgica mediada na página 255 O aumento nas concentrações de por IgE, especialmente alergia alimen- IgE resulta da produção tanto de IgE tar e uma de suas principais manifes- específica aos parasitas quanto de IgE tações, a dermatite atópica. Em re- inespecífica3,4. Um mecanismo proposto cém-nascidos e lactentes jovens as- para explicar o aumento nos níveis sintomáticos, as concentrações elevadas de IgE são um totais de IgE é a secreção, por parasitas, de fatores que indicador da probabilidade de desenvolvimento de doença estimulam a produção de IL-4, levando ao aumento dos alérgica, além de serem um indicador prognóstico em níveis de IgE5,6. Não está claro se o aumento na produção adultos com certos tipos de doenças alérgicas crônicas. As de IL-4 também pode promover a produção de IgE especí- concentrações séricas de IgE são altamente variáveis. fica contra alérgenos comuns, porém é concebível que isso Contudo, quando os níveis de IgE são comparados em possa ocorrer, pelo menos em alguns pacientes. Quando a indivíduos alérgicos e não alérgicos, a concentração média doença parasitária intestinal é tratada com sucesso por de IgE nos indivíduos alérgicos é sempre mais alta do que meio de drogas antiparasitas, observou-se que os níveis nos não alérgicos. Dados recentes sugerem que os mastó- séricos de IgE diminuem consideravelmente com o tempo. citos podem contribuir para as respostas inflamatórias Contudo, quando anticorpos IgE antiparasita coexistem mediadas pelos eosinófilos. Os mastócitos podem ser ativa- com anticorpos IgE antialergênicos, o efeito da diminui- dos por antígeno e imunoglobulina E via liberação de ção nos níveis de IgE antiparasita e IgE total sobre as proteases, leucotrienos, mediadores de lipídios e histami- manifestações da alergia respiratória é variável e ainda na, contribuindo para a inflação do tecido e permitindo o controverso. recrutamento de eosinófilos para o tecido. A observação em países em desenvolvimento, com alta Concentrações elevadas de IgE também podem ser carga de infecções parasitárias, sugeriu um efeito protetor observadas em certas infecções, como HIV e hepatite das infecções parasitárias contra as manifestações alérgi- cas mediadas pela IgE. Nesses países, a prevalência de doenças atópicas é muito menor do que nas nações indus- 1. MD, Professor and Chairman, Department of Pediatrics, Health Science Center, Louisiana State University, New Orleans, LA, USA. trializadas. As infecções parasitárias se correlacionam com 2. MD, Fellow in Training, Allergy/Immunology Division, Health Science a produção de interleucina 10 (IL-10) induzida por helmin- Center, Louisiana State University, New Orleans, LA, USA. tos, que, por sua vez, foi inversamente associada a sensi- Como citar este artigo: Sorensen RU, Sakali P. Does parasitic infection bilização alérgica. Esses achados sugerem que as proprie- protect against allergy? J Pediatr (Rio J). 2006;82:241-2. dades antiinflamatórias da IL-10 induzida pela infecção por doi:10.2223/JPED.1514 helmintos podem atenuar a resposta alergênica ou promo- 241 242 Jornal de Pediatria - Vol. 82, Nº4, 2006 A infecção parasitária protege contra a alergia? Sorensen RU & Sakali P ver tolerância7. Essa relação inversa com sensibilidade com alergia respiratória e altos níveis de IgE total, embora reduzida ao teste cutâneo foi demonstrada em infecções por não se saiba exatamente por quanto tempo depois da helmintos, entre eles ascaridíase, tricuríase e ancilostomí- erradicação do parasita os anticorpos IgE anti-áscaris per- ase8. sistem. Com certeza, a presença concomitante de eosino- Também já foi postulado que os níveis elevados de IgE filia sugere infestação parasitária ativa. Na presença de resultantes de infecções parasitárias saturam os receptores concentrações elevadas de IgE e eosinofilia em pacientes de IgE nos mastócitos, impedindo a ligação de quantidades com manifestações alérgicas como dermatite atópica, rinite suficientes de IgE específica contra os alérgenos para ou asma, com ou sem evidência de sensibilização da IgE a produzir testes cutâneos positivos para aeroalérgenos. Esse alérgenos alimentares ou inalantes, é preciso pesquisar achado é consistente com as observações de Nielsen et al. ativamente e descartar a possibilidade de infestação para- de que a liberação de histamina por basófilos em pacientes sitária. O estudo de Medeiros et al. mostra ainda que em infectados por Toxocara canis ou Ascaris suum está relaci- pacientes com infestações parasitárias e sintomas alérgi- onada à proporção de IgE específica contra o parasita em cos, a coexistência de anticorpos IgE específicos antipara- relação à IgE sérica total. Na verdade, o estímulo de uma sita e antialergênicos deve ser considerada e estudada. resposta policlonal intensa pela IgE pode ser um mecanismo Para o manejo da doença parasitária com alergia respi- pelo qual os parasitas tentam evitar os efeitos protetores ratória coexistente, o relato de Medeiros et al. sugere dos anticorpos IgE parasita-específicos9. claramente que, pelo menos em algumas populações de A inibição de manifestações alérgicas em doenças para- pacientes, as infestações parasitárias e a elevação dos sitárias é reforçada ainda pelo aumento das manifestações anticorpos IgE totais e específicos antiparasita não ofere- de alergia depois do tratamento da doença parasitária, cem proteção significativa contra o desenvolvimento de conforme relatam alguns autores. alergia. Assim, o manejo adequado da infecção parasitária No presente número do Jornal de Pediatria, Medeiros et e das alergias respiratórias deve ser feito simultaneamente, como requerido, sem receio de que o tratamento de uma al. tratam da relação entre doenças alérgicas, inclusive condição possa exacerbar a outra. rinite, dermatite atópica e especialmente asma, e as mani- festações de Ascaris intestinal em uma população jovem no Norte do Brasil10. Um total de 101 pacientes do sexo masculino ou feminino com asma e/ou rinite alérgica, com idade entre 12 e 21 anos, foram selecionados para avalia- Referências ção. Todos os pacientes apresentavam evidência de sensi- 1. Turner H, Kinet JP. Signaling through the high affinity IgE bilização por aeroalérgenos comprovada por altos níveis de receptor Fc epsilon RI. Nature. 1999;25:B24-30. anticorpos IgE específicos detectados in vitro ou por teste 2. Delespesse G, Sarfati M, Wu C, Fournier S, Letellier M. The low cutâneo. As infecções parasitárias foram avaliadas pela affinity receptor for IgE. Immunol Rev. 1992;125:77-97. 3. Rosenberg EB, Whalen GE, Bennich H, Johansson SG . Increasing análise clássica de fezes e títulos de IgE específica anti- circulating IgE in a new parasitic disease: human intestinal áscaris. Foi observada eosinofilia em quase 50% dos parti- capillariasis. N Engl J Med. 1970;283:1148-9. cipantes, e a IgE anti-áscaris foi positiva em 73% dos 4. Rosenberg EB, Polmar SH, Whalen GE. Increased circulating IgE in trichinosis. Ann Intern Med. 1971;75:575-8. indivíduos, embora o exame parasitológico das fezes tenha 5. Dessaint JP, Capron M, Bout D. Quantitative determination of gerado resultados positivos em apenas 34% dos sujeitos do specific IgE antibodies to schistosome antigens and serum IgE estudo. levels in patients with schistosomiasis (S. mansoni or S. haematobium). Clin Exp Immunol. 1975;20:427. Uma observação importante neste estudo foi a preva- 6. Yamaoka KA, Kolb JP, Miyasaka N, Inuo G, Fujita K. Purified lência incomumente alta de infecção parasitária em uma excretory-secretory component of filarial parasite enhances FcepsilonRII/CD23 expression on human splenic B and T cells coorte de paciente atópicos. Essa observação contrasta com and IgE synthesis while potentiating T-helper type 2-related a menor ocorrência de doenças atópicas relatada em áreas cytokine generation from T cells. Immunology. 1994;81:507-12. com alta prevalência de infecções parasitárias11,12. Embora 7. van den Biggelaar AHJ, van Ree R, Rodrigues LC. Decreased atopy in children infected with Schistosoma haematobium: a diversos controles de interesse não tenham sido levados em
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