Serum Immunoglobulin G4 Antibodies to the Recombinant Antigen,<i>Ll</i>‐SXP‐1, Are Highly Specific for<i>Loa loa</i>Infection

Klion, Amy D.; Vijaykumar, Aarthi; Oei, Tamara N.; Martin, Brian K.; Nutman, Thomas B.

doi:10.1086/345873

Cited by 56 publications

(41 citation statements)

References 22 publications

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“…2A), bacterially produced recombinant LlSXP-1 showed (Fig. 2B), but with significant loss of sensitivity (Table 2), as has been previously reported (14). A full-length LlSXP-1 cDNA was constructed as a fusion protein with Ruc.…”

Section: Lips Detection Of Anti-llsxp-1 Antibodies For Diagnosis Of Lsupporting

confidence: 70%

“…A detailed summary of the patient sera used is shown in Table 1. Some of the samples had also previously been analyzed by an LlSXP-1 ELISA, as described elsewhere (14).…”

Section: Methodsmentioning

confidence: 99%

“…pREN2, a mammalian Renilla luciferase (Ruc) expression vector, was used to generate all plasmids (5). LlSXP-1 was amplified from an existing plasmid (14) by PCR, using the following gene-specific linker-primer adapter sequences: 5Ј-GAGGGATCCAATTCGGC ACGAGCAGAA-3Ј and 5Ј-GAGCTCGAGTTATTTTGGACGAAGTGC-3Ј. Following the PCR, the product was restricted with BamHI and XhoI and ligated into BamHI-XhoI-cut pREN2.…”

Section: Methodsmentioning

confidence: 99%

“…A promising alternative to crude antigenbased immunoassays employs defined, recombinant L. loa antigens that show high sensitivity and specificity. One such antigen, LlSXP-1, a member of the Sxp1/RAL family of nematode proteins, employed in an immunoglobulin G4 (IgG4)-based ELISA, was shown to be a highly specific (Ͼ99%) but relatively insensitive (56%) method for diagnosis of L. loa infection (14). Despite its low sensitivity, the high predictive value of a positive result in select clinical settings was encouraging.…”

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confidence: 99%

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Rapid, Novel, Specific, High-Throughput Assay for Diagnosis of Loa loa Infection

et al. 2008

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The ability to diagnose Loa loa infection readily and accurately remains a demanding task. Among the available diagnostic methods, many are impractical for point-of-care field testing. To investigate whether luciferase immunoprecipitation systems (LIPS) can be used for rapid and specific diagnosis of L. loa infection, a LIPS assay was developed based on immunoglobulin G (IgG) and IgG4 subclass antibodies to a recombinant L. loa SXP-1 (designated LlSXP-1) antigen and tested with sera from healthy controls or patients with proven infection with L. loa, Mansonella perstans, Onchocerca volvulus, Strongyloides stercoralis, or Wuchereria bancrofti. A LIPS test measuring IgG antibody against LlSXP-1 readily differentiated L. loa-infected from uninfected patients and demonstrated markedly improved sensitivity and specificity compared with an LlSXP-1 IgG4-based enzyme-linked immunosorbent assay (67% sensitivity and 99% specificity). No significant immunoreactivity was observed with S. stercoralisinfected sera, but a small number of patients infected with O. volvulus, M. perstans, or W. bancrofti showed positive immunoreactivity. Measuring anti-IgG4-specific antibodies to LlSXP-1 showed a significant correlation (r ϳ 0.85; P < 0.00001) with the anti-IgG results but showed no advantage over measuring the total IgG response alone. In contrast, a rapid LIPS format (called QLIPS) in which the tests are performed in less than 15 minutes under nonequilibrium conditions significantly improved the specificity for cross-reactive O. volvulus patient sera (100% sensitivity and 100% specificity). These results suggest that LIPS (and the even more rapid test QLIPS) represents a major advance in the ability to diagnose L. loa infection and may have future applications for point-of-care diagnostics.The development of rapid diagnostic assays for onchocerciasis (22) and lymphatic filariasis (20) has not only simplified the care of individual patients with these filarial infections but also allowed accurate and cost-effective geographic mapping for the purpose of mass chemotherapy in areas of endemicity (21) and for use in the certification process of elimination (15). Nevertheless, the coendemicity of loiasis with these and other filarial infections of humans remains an issue because of species-specific differences in the responses to available antifilarial therapies. This has been of particular concern in the setting of both the African Program for Onchocerciasis Control (APOC) and the Global Program for the Elimination of Lymphatic Filariasis (GPELF), where mass drug administration has ground to a halt in certain areas of Africa because of deaths related to ivermectin administered as part of mass treatment programs for onchocerciasis control (3,12).Although the definitive diagnosis of Loa loa infection can be made morphologically by identifying microfilariae in the blood or, rarely, after surgical removal of the adult worm (typically from its subconjunctival location), a proportion of infected individuals are amicrofilaremic (9, 13). PC...

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Section: Lips Detection Of Anti-llsxp-1 Antibodies For Diagnosis Of Lsupporting

confidence: 70%

“…A detailed summary of the patient sera used is shown in Table 1. Some of the samples had also previously been analyzed by an LlSXP-1 ELISA, as described elsewhere (14).…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Rapid, Novel, Specific, High-Throughput Assay for Diagnosis of Loa loa Infection

et al. 2008

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“…Cold Spring Harbor Laboratory Press on May 11, 2018 -Published by genome.cshlp.org Downloaded from SXP-1 antigen used as a filarial diagnostic tool (Dissanayake et al 1992(Dissanayake et al , 1994Klion et al 2003).…”

Section: Strongyloides Comparative Genomicsmentioning

confidence: 99%

Comparative Genomics of Gene Expression in the Parasitic and Free-Living Nematodes Strongyloides stercoralis and Caenorhabditis elegans

Mitreva¹,

McCarter²,

Martin³

et al. 2004

Genome Res.

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Although developmental timing of gene expression is used to infer potential gene function, studies have yet to correlate this information between species. We analyzed 10,921 ESTs in 3311 clusters from first-and infective third-stage larva (L1, L3i) of the parasitic nematode Strongyloides stercoralis and compared the results to Caenorhabditis elegans, a species that has an L3i-like dauer stage. In the comparison of S. stercoralis clusters with stage-specific expression to C. elegans homologs expressed in either dauer or nondauer stages, matches between S. stercoralis L1 and C. elegans nondauer-expressed genes dominated, suggesting conservation in the repertoire of genes expressed during growth in nutrient-rich conditions. For example, S. stercoralis collagen transcripts were abundant in L1 but not L3i, a pattern consistent with C. elegans collagens. Although a greater proportion of S. stercoralis L3i than L1 genes have homologs among the C. elegans dauer-specific transcripts, we did not uncover evidence of a robust conserved L3i/dauer 'expression signature.' Strikingly, in comparisons of S. stercoralis clusters to C. elegans homologs with RNAi knockouts, those with significant L1-specific expression were more than twice as likely as L3i-specific clusters to match genes with phenotypes. We also provide functional classifications of S. stercoralis clusters.

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Loa loa Pathogenesis in Humans

Paul

2015

Human Emerging and Re‐emerging Infections

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Serum Immunoglobulin G4 Antibodies to the Recombinant Antigen,Ll‐SXP‐1, Are Highly Specific forLoa loaInfection

Cited by 56 publications

References 22 publications

Rapid, Novel, Specific, High-Throughput Assay for Diagnosis of Loa loa Infection

Rapid, Novel, Specific, High-Throughput Assay for Diagnosis of Loa loa Infection

Comparative Genomics of Gene Expression in the Parasitic and Free-Living Nematodes Strongyloides stercoralis and Caenorhabditis elegans

Loa loa Pathogenesis in Humans

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