Searching for biomarkers: humoral response profiling with luciferase immunoprecipitation systems

Burbelo, Peter D.; Ching, Kathryn H.; Bren, Kathleen E.; Iadarola, Michael J.

doi:10.1586/epr.11.23

Cited by 26 publications

(29 citation statements)

References 32 publications

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“…Due to the wide dynamic range of the LIPS data, the results for quantitative antibody levels are reported as the geometric mean titers (GMT) Ϯ 95% confidence intervals (CI). Although LIPS offers highly quantitative data that can be used to generate diagnostically useful serodeterminations without predetermined cutoff values (5,7,9), cutoff values for each of the three antigens were generated based on the uninfected New Zealand horse serum samples. A datadriven analytical approach using high-tailed intensity distribution was used to assign cutoff values for the VOVO, DbpA, and DbpB LIPS tests.…”

Section: Methodsmentioning

confidence: 99%

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Antibody Profiling of Borrelia burgdorferi Infection in Horses

Burbelo

Bren

Ching

et al. 2011

Clin. Vaccine Immunol.

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Infection with Borrelia burgdorferi is common in horses and ponies from the New England and mid-Lyme disease caused by the spirochete Borrelia burgdorferi represents an important problem in veterinary medicine due to the wide-spread infection of dogs, cats, and horses in areas where the organism is endemic (3, 30). While most cases of equine B. burgdorferi infection remain asymptomatic, some horses show signs of illness, including sporadic lameness, weight loss, arthritis, and encephalitis (16). Unlike humans, where the first sign of B. burgdorferi infection is erythema migrans skin lesions, the diagnosis of Lyme disease in horses is complex, and diagnostic testing is only one parameter for confirmation (16).A variety of serological tests, including immunofluorescence assays (IFA), Western blotting, and enzyme-linked immunosorbent assays (ELISAs), have been employed to detect human antibodies to B. burgdorferi (29). Considerable progress has been made in employing defined antigenic targets, such as the C6 peptide (1, 20, 27) and other recombinant B. burgdorferi antigens, including BBK07 (18, 19) and decorin binding proteins (Dbp) DbpA and DbpB (21,22,24,28,31,32). Although extensive testing of different antigens and assay formats has been performed for human Lyme disease (29), less is known about the optimal serological diagnosis of equine B. burgdorferi infection. Recently, the C6 SNAP test has been used for the serological diagnosis of equine Lyme disease (23, 26). Unfortunately, Chang and colleagues found that the C6 SNAP test detected only 63% of known, experimentally B. burgdorferiinfected horses, suggesting that this test is suboptimal for the diagnosis of equine infection (26). In light of the poor sensitivity of the currently available C6 SNAP test, a better understanding of humoral responses in B. burgdorferi-infected horses is needed.Luciferase immunoprecipitation systems (LIPS) comprise a relatively new approach for the serological testing of antibodies associated with many different pathogens (5). LIPS is based on employing light-emitting Renilla luciferase-fusion proteins in a liquid-phase immunoprecipitation assay. Serologic testing by LIPS for a variety of human pathogens provides the full exploitation of antibody profiles because of its robustness, multiplex capacity, and high sensitivity and specificity (6,11,12,14,15). Recently, a LIPS test employing a synthetic VOVO antigen consisting of two variants of immunodominant epitopes of the C6 peptide and OspC achieved 98% sensitivity and 100% specificity for the diagnosis of human Lyme disease, but the findings were not statistically different from those of the C6 ELISA (10). LIPS antibody profiling of recombinant DbpA and DbpB also was highly informative (10). In this study, LIPS tests for VOVO, DbpA, and DbpB antigens were used for measuring B. burgdorferi antibodies in horses, and the results were compared to IFA results for the diagnosis of equine B. burgdorferi infection.

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Section: Methodsmentioning

confidence: 99%

“…Luciferase immunoprecipitation systems (LIPS) comprise a relatively new approach for the serological testing of antibodies associated with many different pathogens (5). LIPS is based on employing light-emitting Renilla luciferase-fusion proteins in a liquid-phase immunoprecipitation assay.…”

mentioning

confidence: 99%

Antibody Profiling of Borrelia burgdorferi Infection in Horses

Burbelo

Bren

Ching

et al. 2011

Clin. Vaccine Immunol.

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“…Although RBA is a highly sensitive technique, the requirement of radioactivity remains a major drawback for more common use. The Luciferase immunoprecipitation system (LIPS) (Burbelo, Ching, Bren, & Iadarola, 2011) is an alternative fluid-phase immunoassay that bypasses the requirement of radioactivity. This method utilizes light-emitting recombinant antigens in highthroughput immunoprecipitation formats, which generate autoantibody profiles to identify patient subsets.…”

Section: Autoantibody Discovery By Fluid-phase Immunoassaysmentioning

confidence: 99%

Utility of Autoantibodies as Biomarkers for Diagnosis and Staging of Neurodegenerative Diseases

DeMarshall

Sarkar

Nägele

et al. 2015

International Review of Neurobiology

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“…One alternative fluid-phase immunoassay that does not require radioactivity is Luciferase Immunoprecipitation Systems (LIPS) [19]. LIPS is based on generating light-emitting recombinant antigens which are then used in a high-throughput immunoprecipitation format to generate high quality autoantibody binding data (Fig.…”

Section: Fluid-phase Immunoassays For Detecting Autoantibodiesmentioning

confidence: 99%

New autoantibody detection technologies yield novel insights into autoimmune disease

Burbelo¹,

O’Hanlon²

2014

Current Opinion in Rheumatology

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Purpose of review The purpose of this review is to highlight recent progress in autoantibody detection technologies and describe how these methods are providing novel information and insights into autoimmune disorders. Recent findings In recent years, alternative methods such as comprehensive phage display, fluid-phase immunoassays, and antigen microarrays have been developed for autoantigen discovery and profiling autoantibody responses. Compared to classic approaches such as Western blot and ELISA, these methods show improved diagnostic performance, the ability to measure antibody responses to multiple targets, and/or allow for more quantitative analyses. Specific notable findings include uncovering previously unrecognized autoantigens, the improved classification of patient clinical phenotypes, and the discovery of pathogenic autoantibodies promoting disease. Summary Advances in immunoassay technologies offer many opportunities for understanding the relationship between autoantibody detection and the myriad complex, clinical phenotypes characteristic of most autoimmune diseases. Further simplification and standardization of these technologies may allow routine integration into clinical practice with improved diagnostic and therapeutic outcomes.

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Searching for biomarkers: humoral response profiling with luciferase immunoprecipitation systems

Cited by 26 publications

References 32 publications

Antibody Profiling of Borrelia burgdorferi Infection in Horses

Antibody Profiling of Borrelia burgdorferi Infection in Horses

Utility of Autoantibodies as Biomarkers for Diagnosis and Staging of Neurodegenerative Diseases

New autoantibody detection technologies yield novel insights into autoimmune disease

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