AUTHOR=Djune-Yemeli Linda , Hertz Marla , Nana-Djeunga Hugues C. , Rush Amy , Erdmann-Gilmore Petra , Sprung Robert , Bopda Jean Gabin , Townsend Reid , Netongo Palmer Masumbe , Kamgno Joseph , Budge Philip J. 

TITLE=Longitudinal study of cross-reactive antigenemia in individuals with high Loa loa microfilarial density reveals promising biomarkers for distinguishing lymphatic filariasis from loiasis

JOURNAL=Frontiers in Parasitology

VOLUME=2

YEAR=2023

URL=https://www.frontiersin.org/journals/parasitology/articles/10.3389/fpara.2023.1292837

DOI=10.3389/fpara.2023.1292837

ISSN=2813-2424

ABSTRACT=<sec><title>Background and methods</title><p>Circulating <italic>Loa loa</italic> antigens are often detected in individuals with heavy <italic>L. loa</italic> infections by diagnostic tests for lymphatic filariasis (LF) caused by <italic>Wuchereria bancrofti</italic>. 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 <italic>L. loa</italic> antigens might be promising biomarkers for distinguishing true LF from loiasis, we screened for <italic>L. loa</italic> antigens in a group of individuals with heavy <italic>L. loa</italic> 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 <italic>L. loa</italic> antigens by liquid chromatography-tandem mass spectrometry (LC-MS/MS) from baseline and 15-month plasma samples.</p></sec><sec><title>Principal findings and conclusions</title><p>Among 73 FTS-positive (FTS+) and 13 FTS-negative (FTS-) participants with high <italic>L. loa</italic> 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 &gt;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.</p></sec>