Table_3_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：循环性罗阿丝虫抗原常通过检测由丝虫病（LF）病原体布氏吴策线虫引起的淋巴丝虫病（LF）来在重感染个体中检测到。这对罗阿丝虫共病区的LF映射和根除努力构成了重大挑战。然而，这也为识别罗阿丝虫的抗原生物标志物提供了机会。为了确定哪些罗阿丝虫抗原可能是区分真实LF与罗阿丝虫病的有前景的生物标志物，我们在喀麦隆奥科拉卫生区的重感染罗阿丝虫个体中筛选了罗阿丝虫抗原。在这项纵向研究中，参与者通过丝虫病测试条（FTS）、ELISA和蛋白质印迹法检测交叉反应性抗原血症，并在入组后6、9、12和15个月监测FTS状态。然后，我们通过液相色谱-串联质谱法（LC-MS/MS）从基线和15个月血浆样本中鉴定了特定的循环罗阿丝虫抗原。主要发现与结论：在73名FTS阳性（FTS+）和13名FTS阴性（FTS-）且罗阿丝虫微丝虫载量高的参与者中，83%在整个研究过程中保持了他们的FTS状态，而17%至少经历了一次FTS转换事件（从FTS+变为FTS-或反之）。通过蛋白质印迹法在FTS+和FTS-血清中检测到交叉反应性抗原，而FTS、蛋白质印迹法和ELISA方法在抗原检测上的一致性较差。通过LC MS/MS在测试样本中检测到一种蛋白质家族，即一组Nas-14金属蛋白酶，包括FTS-样本，在超过80%的样本中。这些数据表明Nas-14是一种有前景的罗阿丝虫生物标志物，可能能够区分罗阿丝虫病与淋巴丝虫病。