Parasite enzymes as a tool to investigate immune responses

Abstract

Previous evidences reported by us and by other authors revealed the presence of IgG in sera of Schistosoma mansoni-infected patients to immunodominant antigens which are enzymes. Besides their immunological interest as possible inductors of protection, several of these enzyme antigens might be also interesting markers of infection in antibody-detecting immunocapture assays which use the intrinsic catalytic property of these antigens. It was thus thought important to define some enzymatic and immunological characteristics of these molecules to better exploit their use as antigens. Four different enzymes from adult worms were partially characterized in their biochemical properties and susceptibility to react with antibodies of infected patients, namely alkaline phosphatase (AKP, Mg2+, pH 9.5), type I phosphodiesterase (PDE, pH 9.5), cysteine proteinase (CP, dithiothreitol, pH 5.5) and N-acetyl-beta-D-glucosaminidase (NAG, pH 5.5). The AKP and PDE are distinct tegumental membrane-bound enzymes whereas CP and NAG are soluble acid enzymes. Antibodies in infected human sera differed in their capacity to react with and to inhibit these enzyme antigens. Possibly, the specificity of the antibodies related to the extent of homology between the parasite and the host enzyme might be in part responsible for the above differences. The results are also discussed in view of the possible functional importance of these enzymes.

Diagnosing Schistosomiasis

“…A sensitivity of 90% was reached by identification of antibodies against the alkaline phosphatase present in the worm's tegument. Until now, from 17 reported enzymes, this was the only which was surveyed in the diagnosis of the infection but it did not offer any advantage on the rough antigens in the differentiation between previous and active infection (Cesari et al 1992).…”

Immunoprotection of Mice against Schistosomiasis Mansoni Using Solubilized Membrane Antigens

“…Anti-AP antibodies circulating in chronically S. mansoni -infected mice did not significantly inhibit the AP activity [18], [25] suggesting that the enzyme active site is not exposed to the immune effectors, and excluding that a functional blocking of this key metabolic enzyme could be responsible for the immune damage to the parasite. However, after PZQ treatment, AP and other molecules (Sm28, actin, etc) becomes critically exposed [18], [52].…”

“…Some of the antigens found in the adult worm n -butanol extract (AWBE) are key tegumental surface enzymes like alkaline phosphate (AP), type 5 phosphodiesterase (PDE-5), acid phosphatase (AcP), Ca 2+ -ATPase and acetylcholinesterase (AChE) [24], [25]. AP is recognized by Schistosoma -infected human and mouse sera [26]; after treatment with PZQ, AP is exposed on the surface and circulating anti-AP antibodies now inhibit the activity [18].…”

Caracterização molecular das nucleotídeo pirofosfatases/ fosfodiesterases de Schistosoma mansoni e investigação como antígenos vacinais.

“…Somando nossos dados a esse modelo, possuímos uma forte evidência da presença de poros no membranocálice, que permitiriam a passagem do substrato e dos anticorpos, cuja existência é discutida na literatura (BRASCHI; BORGES; . A descrição de que pessoas infectadas com S. mansoni apresentam anticorpos circulantes capazes de inibir parcialmente a atividade fosfodieterase em extratos proteicos de vermes adultos (CESARI et al, 1992;CESARI, 1990) também reforça essa hipótese. No entanto, não foi determinado o mecanismo de inibição da atividade enzimática mediada pelos anticorpos.…”

“…Pessoas infectadas apresentam naturalmente anticorpos capazes de inibir duas dessas proteínas, SmNPP-5a e SmFA (CESARI et al, 1992;CESARI, 1990) e como seus parasita são aparentemente imunes a esses anticorpos, poderímaos concluir que esses antígenos não seriam efetivos em induzir uma resposta imune eficaz contra a infecção. Porém é importante lembrar-se que existem indivíduos de áreas endêmicas naturalmente resistentes e que tanto essas pessoas quanto aquelas infectadas apresentam anticorpos contra antígenos, que quando usados como vacina são eficazes em diminuir a taxa de infecção do schistosoma.…”