Increased ShTAL1 IgE responses post-Praziquantel treatment may be associated with a reduced risk to re-infection in a Ghanaian S. haematobium-endemic community.
Increased ShTAL1 IgE responses post-Praziquantel treatment may be associated with a reduced risk to re-infection in a Ghanaian S. haematobium-endemic community.
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DOI：
10.1371/journal.pntd.0010115
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发表时间：
2022-03
影响因子：
3.8
通讯作者：
Boakye DA
中科院分区：
文献类型：
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作者：
Asuming-Brempong EK;Ayi I;van der Puije W;Gyan BA;Larbi IA;Ashong Y;Frempong NA;Quartey JK;Otchere J;Jones FM;Wilson S;Dunne DW;Boakye DA
最近在曼氏血吸虫流行区的研究证据表明，年龄相关的免疫力与曼氏血吸虫特异性表皮变应原样蛋白1（SmTAL 1）的IgE滴度呈正相关。SmTAL 1与S.血吸虫特异性TAL 1（ShTAL 1）已经得到验证，但仍不清楚是否类似的年龄和免疫相关的趋势特征ShTAL 1。这项基于社区的干预研究旨在评估吡喹酮（PZQ）治疗后ShTAL 1 IgE应答是否与S.埃及血吸虫这项研究在加纳中部地区的Agona Agodom进行，涉及114名6至55岁的参与者。在基线和PZQ治疗后7周（随访）收集EDTA血液样品。基线和随访时抗沙门氏菌特异性IgG 1、IgG 4和IgE抗体的滴度。使用夹心ELISA测量血浆样本中的血原虫特异性成虫抗原（ShAWA）、sh特异性可溶性卵抗原（ShSEA）和sh特异性表皮过敏原样1蛋白（ShTAL 1）。两个时间点的参与者还提供粪便和尿液，用于通过显微镜进行蠕虫卵检测。S.在基线时，血红蛋白为22.80%，在随访时下降至3.50%。减蛋率为99.87%。PZQ治疗后7周，ShTAL 1-IgE的总体血浆水平增加，并且随着年龄的增加而增加;血吸虫感染率和感染强度下降。对于鼠伤寒沙门氏在随访时虫卵阴性的嗜血杆菌感染参与者中（N = 23），治疗前所有年龄组均观察到ShTAL 1-IgE的最低中位数水平，而随访时12岁及以上参与者的中位数水平显著增加;在11岁或以下的参与者中保持最低水平。在单变量分析中，年龄在12岁或以上意味着ShTAL 1-IgE阳性的可能性增加[12-14岁（cOR = 9.64，95% CI = 2.09-44.51; p = 0.004）; 15岁以上（cOR = 14.26，95% CI = 3.10-65.51; p = 0.001）]，在调整混杂因素后仍有显著性[12-14年（aOR = 22.34，95%CI = 2.77-180.14; p = 0.004）; ≥15岁（aOR = 51.82，95%CI = 6.44-417.17; p < 0.001）]。相反，在随访时几乎检测不到中位ShTAL 1-IgG 4滴度。这些发现表明，PZQ治疗7周后ShTAL 1的IgE水平升高可能与再感染风险降低有关，并增加了大量证据，表明治疗诱导的ShTAL 1抗原在血吸虫病感染中具有保护作用。从这项工作中也很清楚，除了坚持S。在随访时，血凝素阳性、ShTAL 1-IgG 4水平升高可指示对再感染的易感性。这些结果对疫苗开发以及将大规模化疗计划的范式从“一刀切”的方法转变为流行地区更具亚组/参与者特定性的策略具有重要影响。目前世界卫生组织（WHO）批准的防治血吸虫病的策略是对生活在流行社区的受试者给予吡喹酮（PZQ）。由于担心对PZQ的抗性的潜在发展，已经进行了广泛的研究以发现能够引起保护性免疫（特别是针对童虫的保护性免疫）的推定的候选抗原。已发现的这种抗原家族之一是曼氏血吸虫表皮变应原样蛋白1至13（SmTAL 1 -13），其中前六种已被广泛研究。虽然不存在于3小时的童虫中，但已发现SmTAL 1抗原诱导交叉反应性IgE，其也识别存在于尾蚴和童虫表面上的SmTAL 3和SmTAL 5抗原。各种流行病学研究表明，SmTAL 1诱导的IgEs是产生感染/再感染抵抗力的潜在良好标志物/指标。在这项以社区为基础的干预研究中，我们试图确定是否实现了对埃及血吸虫TAL 1 IgE的结果。PZQ治疗后7周可预测对S.埃及血吸虫我们的工作不仅评估了与ShTAL 1相关的免疫反应，而且还探索了可能表征参与者对S.埃及血吸虫
Evidence from recent studies in Schistosoma mansoni-endemic areas show an age-associated immunity that is positively correlated with IgE titres to Schistosoma mansoni-specific tegumental allergen-like protein 1 (SmTAL1). The structural homology between SmTAL1 and the S. haematobium-specific TAL1 (ShTAL1) has been verified, yet it remains unclear whether similar age- and immune-associated trends characterize ShTAL1. This community-based intervention study was conducted to assess whether ShTAL1IgE responses post-treatment with praziquantel (PZQ) might be associated with a reduced risk to re-infection with S. haematobium. This study was conducted at Agona Abodom, Central Region, Ghana, and involved 114 participants aged 6 to 55 years. EDTA blood samples were collected at baseline and 7 weeks after PZQ treatment (Follow-up). Baseline and Follow-up titres of specific IgG1, IgG4, and IgE antibodies to the S. haematobium-specific adult worm antigen (ShAWA), the Sh-specific soluble egg antigen (ShSEA), and the Sh-specific tegumental-allergen-like 1 protein (ShTAL1) in plasma samples were measured using sandwich ELISA. Participants at both time points also provided stool and urine for helminth egg detection by microscopy. Prevalence of S. haematobium at baseline was 22.80%, and decreased to 3.50% at Follow-up. The egg reduction rate (ERR) was 99.87%. Overall plasma levels of ShTAL1-IgE increased 7 weeks post-PZQ treatment, and with increasing age; whiles S. haematobium infection prevalence and intensity decreased. For S. haematobium-infected participants who were egg-negative at Follow-up (N = 23), minimal median levels of ShTAL1-IgE were observed for all age groups prior to treatment, whilst median levels increased considerably among participants aged 12 years and older at Follow-up; and remained minimal among participants aged 11 years or less. In the univariate analysis, being aged 12 years or older implied an increased likelihood for ShTAL1-IgE positivity [12–14 years (cOR = 9.64, 95% CI = 2.09–44.51; p = 0.004); 15+ years (cOR = 14.26, 95% CI = 3.10–65.51; p = 0.001)], and this remained significant after adjusting for confounders [12–14 years (aOR = 22.34, 95% CI = 2.77–180.14; p = 0.004); ≥15 years (aOR = 51.82, 95% CI = 6.44–417.17; p < 0.001)]. Conversely, median ShTAL1-IgG4 titres were hardly detectible at Follow-up. These findings demonstrate that increased IgE levels to ShTAL1 7 weeks after PZQ treatment could be associated with a reduced risk to re-infection, and adds to the large body of evidence suggesting a protective role of the treatment-induced ShTAL1 antigen in schistosomiasis infections. It was also quite clear from this work that apart from being persistently S. haematobium-positive, elevated ShTAL1-IgG4 levels at Follow-up could be indicative of susceptibility to re-infection. These outcomes have important implications in vaccine development, and in shifting the paradigm in mass chemotherapy programmes from a ‘one-size-fits-all’ approach to more sub-group-/participant-specific strategies in endemic areas. The current World Health Organization (WHO)—approved strategy for combating schistosomiasis, is the administration of praziquantel (PZQ) to subjects living in endemic communities. Due to concerns of the potential development of resistance to PZQ, there have been extensive studies to find putative candidate antigens capable of eliciting protective immunity particularly against the schistosomulum. One of such family of antigens discovered is the Schistosoma mansoni tegumental allergen-like proteins 1 through 13 (SmTAL1–13), of which the first six have been extensively studied. Although not present in the 3-hour schistosomulum, the SmTAL1 antigen has been found to induce cross-reactive IgEs that also recognize the SmTAL3 and SmTAL5 antigens present on the surface of cercariae and schistosomulae. Various epidemiological studies have indicated IgEs induced by SmTAL1 as potentially good markers/indicators for developing resistance to infection/re-infection. In this community-based intervention study, we sought to determine whether outcomes realized for Schistosoma haematobium TAL1 IgE. 7 weeks-post PZQ treatment would be predictive of protection against re-infection with S. haematobium. Our work not only assesses immune responses associated with ShTAL1, but also explores immune profiles that may characterize participants susceptible or resistant to re-infection with S. haematobium.
DOI：
10.1093/infdis/jis676
发表时间：
2013-01-15
期刊：
The Journal of infectious diseases
影响因子：
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作者：
Pinot de Moira A;Sousa-Figueiredo JC;Jones FM;Fitzsimmons CM;Betson M;Kabatereine NB;Stothard JR;Dunne DW
通讯作者：
Dunne DW