Cross-reactive antigenic domains of the flagellin protein of Borrelia burgdorferi

Luft, Benjamin J.; Dunn, John J.; Dattwyler, Raymond J.; Gorgone, G; Gorevic, Peter D.; Schubach, William H.

doi:10.1016/0923-2508(93)90009-q

Cited by 26 publications

(28 citation statements)

References 22 publications

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“…The panels described here offer sera from patients with look-alike diseases (fibromyalgia, infectious mononucleosis, multiple sclerosis, rheumatoid arthritis, syphilis, and severe periodontitis) that are documented as causing cross-reactivity in serologic assays for Lyme disease (27,28) and/or are a differential diagnosis for at least one of the stages of Lyme disease (2). Syphilis and some cases of severe periodontitis are caused by the spirochetes Treponema pallidum and Treponema denticola, respectively, and anti- bodies to both organisms have been shown to be cross-reactive with Borrelia antigens (29). No cross-reactivity to the Lyme disease EIA and two-tiered test was observed with sera from patients with severe periodontitis.…”

Section: Discussionmentioning

confidence: 99%

Collection and Characterization of Samples for Establishment of a Serum Repository for Lyme Disease Diagnostic Test Development and Evaluation

et al. 2014

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Serological assays and a two-tiered test algorithm are recommended for laboratory confirmation of Lyme disease. In the United States, the sensitivity of two-tiered testing using commercially available serology-based assays is dependent on the stage of infection and ranges from 30% in the early localized disease stage to near 100% in late-stage disease. Other variables, including subjectivity in reading Western blots, compliance with two-tiered recommendations, use of different first-and second-tier test combinations, and use of different test samples, all contribute to variation in two-tiered test performance. The availability and use of sample sets from well-characterized Lyme disease patients and controls are needed to better assess the performance of existing tests and for development of improved assays. To address this need, the Centers for Disease Control and Prevention and the National Institutes of Health prospectively collected sera from patients at all stages of Lyme disease, as well as healthy donors and patients with look-alike diseases. Patients and healthy controls were recruited using strict inclusion and exclusion criteria. Samples from all included patients were retrospectively characterized by two-tiered testing. The results from two-tiered testing corroborated the need for novel and improved diagnostics, particularly for laboratory diagnosis of earlier stages of infection. Furthermore, the two-tiered results provide a baseline with samples from well-characterized patients that can be used in comparing the sensitivity and specificity of novel diagnostics. Panels of sera and accompanying clinical and laboratory testing results are now available to Lyme disease serological test users and researchers developing novel tests.

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Section: Discussionmentioning

confidence: 99%

Collection and Characterization of Samples for Establishment of a Serum Repository for Lyme Disease Diagnostic Test Development and Evaluation

et al. 2014

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“…Differences could also have been due to different sensitivities and/or distinct specificities of the two tests. Flagellin protein (IDEIA) is a highly immunogenic antigen and elicits an early and strong immune response but is prone to crossreactivity (13). In the Liaison test, OspC is one of the most immunodominant antigens in the IgM immune response, whereas the VlsE protein elicits a strong IgG response (1,18).…”

Section: Discussionmentioning

confidence: 99%

Humoral Immune Responses in Patients with Lyme Neuroborreliosis

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Ogrinc

Strle

et al. 2010

Clin Vaccine Immunol

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“…Thus, some immunoassays consist of purified flagella alone (114,115,138,148), whereas in others, flagellin is added to enrich the antigenic mixture (174). Unfortunately, although highly immunogenic, this antigen is highly cross-reactive with antigens in other bacteria, particularly when denatured, as in immunoblots (35,91,179). Certain flagellin epitopes are also cross-reactive with antigens found in mammalian tissues such as neural tissues, synovium, and myocardial muscle (1,179).…”

Section: Immunologic Diagnosis Of B Burgdorferi Sensu Lato Infectionmentioning

confidence: 99%

“…Unfortunately, although highly immunogenic, this antigen is highly cross-reactive with antigens in other bacteria, particularly when denatured, as in immunoblots (35,91,179). Certain flagellin epitopes are also cross-reactive with antigens found in mammalian tissues such as neural tissues, synovium, and myocardial muscle (1,179). The internal portion of the flagellin molecule, containing the variable, genus-specific immunodominant domain, is less cross-reactive with antigens of other bacteria than the whole protein (101,179,274).…”

Section: Immunologic Diagnosis Of B Burgdorferi Sensu Lato Infectionmentioning

confidence: 99%

“…Certain flagellin epitopes are also cross-reactive with antigens found in mammalian tissues such as neural tissues, synovium, and myocardial muscle (1,179). The internal portion of the flagellin molecule, containing the variable, genus-specific immunodominant domain, is less cross-reactive with antigens of other bacteria than the whole protein (101,179,274). The flagellar outer sheath protein FlaA, with a molecular size of 37 kDa, is another immunodominant antigen, especially in early disease (7,84,104,246).…”

Section: Immunologic Diagnosis Of B Burgdorferi Sensu Lato Infectionmentioning

confidence: 99%

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Diagnosis of Lyme Borreliosis

et al. 2005

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A large amount of knowledge has been acquired since the original descriptions of Lyme borreliosis (LB) and of its causative agent, Borrelia burgdorferi sensu stricto. The complexity of the organism and the variations in the clinical manifestations of LB caused by the different B. burgdorferi sensu lato species were not then anticipated. Considerable improvement has been achieved in detection of B. burgdorferi sensu lato by culture, particularly of blood specimens during early stages of disease. Culturing plasma and increasing the volume of material cultured have accomplished this. Further improvements might be obtained if molecular methods are used for detection of growth in culture and if culture methods are automated. Unfortunately, culture is insensitive in extracutaneous manifestations of LB. PCR and culture have high sensitivity on skin samples of patients with EM whose diagnosis is based mostly on clinical recognition of the lesion. PCR on material obtained from extracutaneous sites is in general of low sensitivity, with the exception of synovial fluid. PCR on synovial fluid has shown a sensitivity of up to >90% (when using four different primer sets) in patients with untreated or partially treated Lyme arthritis, making it a helpful confirmatory test in these patients. Currently, the best use of PCR is for confirmation of the clinical diagnosis of suspected Lyme arthritis in patients who are IgG immunoblot positive. PCR should not be used as the sole laboratory modality to support a clinical diagnosis of extracutaneous LB. PCR positivity in seronegative patients suspected of having late manifestations of LB most likely represents a false-positive result. Because of difficulties in direct methods of detection, laboratory tests currently in use are mainly those detecting antibodies to B. burgdorferi sensu lato. Tests used to detect antibodies to B. burgdorferi sensu lato have evolved from the initial formats as more knowledge on the immunodominant antigens has been collected. The recommendation for two-tier testing was an attempt to standardize testing and improve specificity in the United States. First-tier assays using whole-cell sonicates of B. burgdorferi sensu lato need to be standardized in terms of antigen composition and detection threshold of specific immunoglobulin classes. The search for improved serologic tests has stimulated the development of recombinant protein antigens and the synthesis of specific peptides from immunodominant antigens. The use of these materials alone or in combination as the source of antigen in a single-tier immunoassay may someday replace the currently recommended two-tier testing strategy. Evaluation of these assays is currently being done, and there is evidence that certain of these antigens may be broadly cross-reactive with the B. burgdorferi sensu lato species causing LB in Europe

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Cross-reactive antigenic domains of the flagellin protein of Borrelia burgdorferi

Cited by 26 publications

References 22 publications

Collection and Characterization of Samples for Establishment of a Serum Repository for Lyme Disease Diagnostic Test Development and Evaluation

Collection and Characterization of Samples for Establishment of a Serum Repository for Lyme Disease Diagnostic Test Development and Evaluation

Humoral Immune Responses in Patients with Lyme Neuroborreliosis

Diagnosis of Lyme Borreliosis

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