Dataset Information

An antibody biomarker associated with Onchocerca volvulus microfilariae identified by proteomics of parasite tissue isolated by laser capture microdissection

ABSTRACT: Onchocerciasis (river blindness), a neglected tropical disease caused by the filarial nematode Onchocerca volvulus, impacts millions of people in sub-Saharan Africa. The World Health Organization coordinates global efforts to eliminate onchocerciasis and has prioritized development of improved diagnostic tests to aid these efforts. Here, we used laser capture microdissection to isolate distinct tissues from histologic sections of O. volvulus worms in subcutaneous nodules removed from onchocerciasis patients. Proteomic analysis identified 2,512 O. volvulus proteins in those tissues, including 264 found only in the microfilariae. From this pool of diagnostic candidates, we selected the putative cuticular collagen OVOC12404 for further study because of its abundance and lack of close homologues in other filarial species. The antigen was localized to the surface of coiled, stretched and tissue microfilariae. IgG antibodies to OVOC12404 were detected by ELISA in plasma from 132 of 160 (81%) onchocerciasis patients. ELISA specificity was 98% based on 42 samples from lymphatic filariasis patients from areas without co-endemic onchocerciasis. In contrast to antibodies to OV16, antibodies to OVOC12404 declined after treatments that cleared O. volvulus microfilariae from the skin. This study showed that proteomic analysis of parasite tissues recovered from histological sections can be used to identify diagnostic targets. Further studies are needed to assess the potential value of an OVOC12404 antibody test as an additional diagnostic tool to support the global program to eliminate onchocerciasis.

INSTRUMENT(S):

ORGANISM(S): Onchocerca Sp. Np-2011 Homo Sapiens (human)

TISSUE(S): Oocyte

SUBMITTER: Byoung-Kyu Cho

LAB HEAD: Young Ah

PROVIDER: PXD057556 | Pride | 2026-07-27

REPOSITORIES: Pride

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			Action	DRS
	20230419_bkc_23-0253_Fischer_Fischer_AFT-199.raw	Raw
	20230419_bkc_23-0253_Fischer_Fischer_AFT-20.raw	Raw
	20230419_bkc_23-0253_Fischer_Fischer_AFT-73.raw	Raw
	20230419_bkc_23-0253_Fischer_Fischer_EO-199.raw	Raw
	20230419_bkc_23-0253_Fischer_Fischer_EO-20.raw	Raw

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An Antibody Biomarker Associated with Onchocerca volvulus Microfilariae Identified by Proteomic Analysis of Parasite Tissues Isolated from Paraffin Embedded O. volvulus Nodules by Laser Capture Microdissection.

Greene Sarah E SE Fischer Kerstin K Di Maggio Lucia S LS Rosa Bruce A BA Huang Yuefang Y Diekmann Irina I Cho Byoung-Kyu BK Lukowski Jessica J Goo Young A YA Mitreva Makedonka M Opoku Nicholas N Weil Gary J GJ Fischer Peter U PU

The American journal of tropical medicine and hygiene 20250603 2

Onchocerciasis (river blindness), a neglected tropical disease caused by the filarial nematode Onchocerca volvulus, impacts millions of people in sub-Saharan Africa. The WHO coordinates global efforts to eliminate onchocerciasis and has prioritized development of improved diagnostic tests to aid these efforts. To find new microfilarial-associated diagnostic targets to help identify active infections, we used laser capture microdissection to isolate embryonic stages from histologic sections of O. ...[more]

PMID: 40460822

Similar Datasets

Project description:Onchocerca volvulus is the agent of onchocerciasis or river blindness and targeted by WHO for elimination. The main strategy is mass drug administration with ivermectin for the duration of the life span of the adult worms. The drug is mainly microfilaricidal, but weak macrofilaricidal effects, after several rounds of treatment, were observed. A small percentage of adult O. volvulus females contain pleomorphic neoplasms and the rate of worms with neoplasms increases with the number of ivermectin treatments. Within a clinical trial of drug combinations that included ivermectin we identified 24 (5.6%) adult females with neoplasms. We assessed the protein inventory of these neoplasms to identify proteins that may be associated with tumor development. We used laser capture microdissection and highly sensitive mass spectrometry analysis to determine the protein inventory of neoplasms. Neoplasm tissue from female worms was analyzed, and compared to normal tissue from the body wall, uterus and intestine from the same worms, and to tissues from females without neoplasms. One female with neoplasms had a few normal stretched microfilariae in the vagina, but no normal embryogenesis was seen in the other two worms. The healthy females showed all intact embryogenesis. In the worms with neoplasms, 151 proteins were detected in the body wall, 215 proteins in the intestine, 47 proteins in the uterus and 1,577 proteins in the neoplasms. Only in the uterus of the female with intrauterine microfilariae an elevated number of proteins (601) was detectable, while in the uteri of the healthy females 1,710 proteins were detected. The majority of the 20 most abundant proteins identified in neoplasms was highly conserved and only two nematode specific proteins were observed. Among the most abundant proteins that were found in neoplasms but not in the other analyzed tissues, were peroxiredoxin, proteases, and proteins related to signal transduction, ribosomal and proteasome activity. Immunolocalization of a calcium binding protein that was detected in neoplasms confirmed the mass spectrometry results. In conclusion, we have developed a system to analyze the proteome of O. volvulus from nodule sections and identified proteins that are potentially linked to the development of neoplasms and may contribute to worm mortality.

Project description:In spite of 40 years of control efforts, onchocerciasis (river blindness) remains one of the most important neglected tropical diseases, with 17 million people affected. The aetiological agent, Onchocerca volvulus, is a filarial nematode with a complex lifecycle involving several distinct stages in the definitive host and blackfly vector. The challenges of obtaining sufficient material have prevented high-throughput studies and the development of novel strategies for disease control and diagnosis. Here, we utilise the closest relative of O. volvulus, the bovine parasite Onchocerca ochengi, to compare stage-specific proteomes and host-parasite interactions within the secretome. We identified a total of 4,260 unique O. ochengi proteins from adult males and females, infective larvae, intrauterine microfilariae, and fluid from intradermal nodules. In addition, 135 proteins were detected from the obligate Wolbachia symbiont. Observed protein families that were enriched in all whole body extracts relative to the complete search database included immunoglobulin-domain proteins, whereas redox and detoxification enzymes and proteins involved in intracellular transport displayed stage-specific overrepresentation. Unexpectedly, the larval stages exhibited enrichment for several mitochondrial-related protein families, including members of peptidase family M16 and proteins which mediate mitochondrial fission and fusion. Quantification of proteins across the lifecycle using the Hi 3 approach supported these qualitative analyses. In nodule fluid, we identified 94 O. ochengi secreted proteins, including two homologs of transforming growth factor and a second member of a novel 6 ShK toxin domain family, which was originally identified from a model filarial nematode (Litomosoides sigmodontis). Strikingly, the 498 bovine proteins identified in nodule fluid were strongly dominated by antimicrobial proteins, especially cathelicidins. This first high-throughput analysis of an Onchocerca spp. proteome highlights its profound complexity and emphasises the extremely close relationship between O. ochengi and O. volvulus. The insights provided here provide new candidates for vaccine development, drug targeting and diagnostic biomarkers.

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