Table_1_Longitudinal study of cross-reactive antigenemia in individuals with high Loa loa microfilarial density reveals promising biomarkers for distinguishing lymphatic filariasis from loiasis.xlsx

Background and methodsCirculating Loa loa antigens are often detected in individuals with heavy L. loa infections by diagnostic tests for lymphatic filariasis (LF) caused by Wuchereria bancrofti. This is a major challenge to LF mapping and elimination efforts in loiasis co-endemic areas. However, it also provides an opportunity to identify antigen biomarkers for loiasis. To determine which L. loa antigens might be promising biomarkers for distinguishing true LF from loiasis, we screened for L. loa antigens in a group of individuals with heavy L. loa infections living in the Okola Health District of Cameroon. In this longitudinal study, participants were tested for cross-reactive antigenemia by filariasis test strip (FTS), ELISA, and western blot, and were monitored for FTS status at 6, 9, 12, and 15 months post-enrollment. We then identified specific circulating L. loa antigens by liquid chromatography-tandem mass spectrometry (LC-MS/MS) from baseline and 15-month plasma samples.Principal findings and conclusionsAmong 73 FTS-positive (FTS+) and 13 FTS-negative (FTS-) participants with high L. loa microfilarial loads, 83% maintained their FTS status over the course of the study, while 17% experienced at least one FTS conversion event (from FTS+ to FTS- or vice versa). Cross-reactive antigens were detected in both FTS+ and FTS- sera by western blot, and there was poor agreement in antigen detection by FTS, western blot, and ELISA methods. One protein family, a group of Nas-14 metalloproteases, was detected by LC MS/MS in >80% of tested samples, including FTS- samples. These data identify Nas-14 as a promising loiasis biomarker potentially capable of distinguishing loiasis from lymphatic filariasis.

背景与方法：在由丝虫病原体 Wuchereria bancrofti 引起的淋巴丝虫病（LF）的诊断测试中，通常可在重感染 Loa loa 的个体中检测到循环 Loa loa 抗原。这给淋巴丝虫病在洛阿丝虫病共患病区的地图绘制和根除工作带来了重大挑战。然而，这也为识别洛阿丝虫病的抗原生物标志物提供了机会。为了确定哪些 Loa loa 抗原可能是有望区分真性淋巴丝虫病与洛阿丝虫病的生物标志物，我们在居住在喀麦隆奥科拉卫生区的重感染 Loa loa 的个体中筛查了 Loa loa 抗原。在本纵向研究中，参与者通过丝虫病测试条（FTS）、酶联免疫吸附测定（ELISA）和Western blot 进行了交叉反应性抗原血症的检测，并在入组后 6、9、12 和 15 个月监测了 FTS 状态。然后，我们从基线和 15 个月血浆样本中通过液相色谱-串联质谱法（LC-MS/MS）鉴定了特定的循环 Loa loa 抗原。主要发现与结论：在 73 名 FTS 阳性（FTS+）和 13 名 FTS 阴性（FTS-）且 Loa loa 微丝蚴负荷量高的参与者中，83% 在研究过程中保持了其 FTS 状态，而 17% 至少经历了一次 FTS 转换事件（从 FTS+ 到 FTS- 或反之）。Western blot 在 FTS+ 和 FTS- 血清中均检测到交叉反应性抗原，而 FTS、Western blot 和 ELISA 方法在抗原检测方面的一致性较差。通过液相色谱-串联质谱法（LC MS/MS）在测试样品的 80% 以上检测到了一种蛋白质家族，即 Nas-14 金属蛋白酶组。这些数据表明 Nas-14 是一种有希望的洛阿丝虫病生物标志物，可能能够区分洛阿丝虫病与淋巴丝虫病。