Expression of antibodies directed to Paracoccidioides brasiliensis glycosphingolipids during the course of paracoccidioidomycosis treatment

Expression of antibodies directed to Paracoccidioides brasiliensis glycosphingolipids during the course of paracoccidioidomycosis treatment
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DOI:
10.1128/cvi.00285-06
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发表时间:
2007-02-01
影响因子:
--
通讯作者:
Straus, Anita H.
Straus, Anita H.
中科院分区:
生物3区
文献类型:
--
作者:
Bertini, Silvio;Colombo, Arnaldo L.;Straus, Anita H.

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副球孢子菌病(PCM)是一种由巴西副球孢子菌引起的肉芽肿性疾病。用酶联免疫吸附试验测定了31例PCM患者血清中抗巴西青霉酸性鞘糖脂(GSL)和葡萄糖神经酰胺抗体的免疫球蛋白类型和同种型。根据治疗阶段分析了38份血清样本的反应性:抗真菌治疗前(n = 10)、治疗1 - 4个月期间(T1-4; n = 9)、治疗5 - 12个月期间(T5-12; n = 9)和治疗后(PT; n = 10)。来自健康受试者(n = 12)的血清用作对照。仅GSL Pb-1抗原(其呈现碳水化合物结构Galf β 1-6(Man α 1-3)Man β 1)与PCM患者血清反应。PCM患者血清不与Pb-2反应,Pb-2缺乏Galf残基,并且被认为是Pb-1的生物合成前体,表明Galf残基对于抗体反应性是必需的。未经治疗的患者的铅-1糖脂引起的免疫球蛋白M(IgM)的生产和随后切换到IgG 1生产的主要免疫应答。抗真菌治疗开始后IgG 1滴度升高(T1-4组),治疗5个月后观察到抗Pb-1抗体滴度普遍降低(T5-12和PT组)。Pb-1抗原是一种末端带有Galf残基的酸性GSL,在PCM患者中作为宿主免疫应答的激发剂具有潜在的应用价值。
Paracoccidioidomycosis (PCM) is a granulomatous disease caused by the dimorphic fungus Paracoccidioides brasiliensis. The immunoglobulin classes and isotypes of antibodies directed to acidic glycosphingolipids (GSLs) and glucosylceramide of P. brasiliensis were determined by enzyme-linked immunosorbent assay of sera from 31 PCM patients. The reactivities of 38 serum samples were analyzed by considering the stage of treatment: before antifungal treatment (n = 10), during 1 to 4 months of treatment (T1-4; n = 9), during 5 to 12 months of treatment (T5-12; n = 9), and posttreatment (PT; n = 10). Sera from healthy subjects (n = 12) were used as controls. Only the GSL Pb-1 antigen, which presents the carbohydrate structure Galf beta 1-6(Man alpha 1-3)Man beta 1, was reactive with the PCM patient sera. The PCM patient sera did not react with Pb-2, which lacks the Galf residue and which is considered the biosynthetic precursor of Pb-1, indicating that the Galf residue is essential for antibody reactivity. The Pb-1 glycolipid from nontreated patients elicited a primary immune response with immunoglobulin M (IgM) production and subsequent switching to IgG1 production. The IgG1 titer increased after the start of antifungal treatment (T1-4 group), and general decreases in the anti-Pb-1 antibody titers were observed after 5 months of treatment (T5-12 and PT groups). The Pb-1 antigen, an acidic GSL with terminal Galf residue, has potential application as an elicitor of the host immune response in patients with PCM.