A Decrease in the Immunoglobulin G Antibody Response against the VlsE Protein of
            <i>Borrelia burgdorferi</i>
            Sensu Lato Correlates with the Resolution of Clinical Signs in Antibiotic-Treated Patients with Early Lyme Disease

Marangoni, Antonella; Sambri, Vittorio; Accardo, Silvia; Cavrini, Francesca; Mondardini, Valeria; Moroni, Alessandra; Storni, Elisa; Cevenini, Roberto

doi:10.1128/cvi.13.4.525-529.2006

Cited by 24 publications

(20 citation statements)

References 43 publications

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“…It is widely recognized that antibiotics given to patients can interfere with the immune response to some antigens (1,5,46). In published studies using either C6 or VlsE as the antigen source, patients who received treatment soon after infection were more likely to have undetectable antibody levels than patients who were treated after the infection had disseminated (38,48).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Recombinant VlsE-Based Liaison Chemiluminescence Immunoassay for Detection ofBorrelia burgdorferiand Diagnosis of Lyme Disease

Ledue

Collins

Young

et al. 2008

Clin Vaccine Immunol

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Recent efforts to improve the serologic diagnosis of Lyme disease have included the use of a synthetic peptide (C6) that reproduces the sequence of invariable region 6 of VlsE, the variable surface antigen of Borrelia burgdorferi. In the present study, the diagnostic performance of DiaSorin's recombinant VlsE-based chemiluminescence immunoassay in 1,947 human serum samples was evaluated. Sensitivity was determined using two serum panels from the CDC. For panel I, we observed sensitivities of 68.4% and 75.6% for subjects with early, localized (n ‫؍‬ 19) or disseminated (n ‫؍‬ 41) disease, respectively. For panel II, we observed sensitivities of 61.5% and 100% for subjects with early (n ‫؍‬ 26) or late-stage (n ‫؍‬ 11) disease, respectively. We observed a specificity of 99.5% for healthy donors (n ‫؍‬ 600) living either in regions of the United States where the disease is endemic or in regions where it is not endemic. Overall, specificity among 207 potentially cross-reactive sera from subjects who had other spirochetal infections, nonspirochetal infections including bacterial and viral infections, or autoimmune or neurologic disease; who were positive for rheumatoid factor or anti-mouse antibodies; or who had been previously vaccinated for Lyme disease was 93.7%. In a direct comparison of 1,038 prospectively collected samples for Lyme disease testing we observed a relative sensitivity of 70%, a relative specificity of 99.1%, and an overall agreement of 97.1% between the DiaSorin recombinant VlsE chemiluminescence immunoassay and the Immunetics peptide-based C6 enzyme-linked immunosorbent assay.

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Section: Discussionmentioning

confidence: 99%

Evaluation of the Recombinant VlsE-Based Liaison Chemiluminescence Immunoassay for Detection ofBorrelia burgdorferiand Diagnosis of Lyme Disease

Ledue

Collins

Young

et al. 2008

Clin Vaccine Immunol

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“…In addition to sera from healthy blood donors (n=20), acute sera (n=23) with high IgM titers against EBV, CMV, VZV, HSV, or finally parvovirus were included for comparison. An instrument analysing Borrelia immunoglobulin M and G by a two step sandwich CLIA (Liaison; DiaSorin, Salugia, Italy) was used [10]. The CLIA consisted of the recombinant antigens OspC (from the strain B.…”

mentioning

confidence: 99%

Comparison of an automated Borrelia indirect chemiluminescent immunoassay (CLIA) with a VlsE/C6 ELISA and Immunoblot

Riesbeck

Hammas

2007

Eur J Clin Microbiol Infect Dis

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“…VlsE could be abnormally expressed or not expressed at all by RST2 spirochetes given that many isolates harbor an incomplete lp28-1 plasmid. Detection of antibody to C 6 , a peptide that reproduces the sequence of the sixth invariable region within the central domain of the VlsE protein of B. burgdorferi, is used currently for the serologic diagnosis of Lyme disease in humans (1,5,9,12,17,18,(20)(21)(22)(23)(24) and in canines (3,7,8,11,14). As the C 6 test emerges as a possible substitute for the twotiered serologic algorithm (1), the absence of portions of lp28-1 in RST2 isolates could represent a problem.…”

mentioning

confidence: 99%

Borrelia burgdorferi Spirochetes That Harbor Only a Portion of the lp28-1 Plasmid Elicit Antibody Responses Detectable with the C ₆ Test for Lyme Disease

Embers

Wormser

Schwartz

et al. 2007

Clin Vaccine Immunol

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Detection of antibody to C 6 , a peptide that reproduces the sequence of the sixth invariable region within the central domain of the VlsE protein of Borrelia burgdorferi, is used currently for the serologic diagnosis of Lyme disease in humans. B. burgdorferi isolates taken from infected humans can be categorized into specific genetic subtypes (designated RST1, -2, and -3) by restriction fragment length polymorphisms in the 16S to 23S rRNA spacer sequence. Many of these, usually categorized as RST2, retain only segments of the linear plasmid lp28-1, which encodes VlsE. The VlsE genetic region is retained, but altered expression of this molecule could affect diagnosis by the C 6 enzyme-linked immunosorbent assay (ELISA). Serum samples from patients infected with each of the three genotypes and from mice infected with three RST2 isolates were tested with the C 6 ELISA. Such isolates elicited marked C 6 responses in infected mice. The sensitivity of C 6 antibody detection in patients infected with RST2 spirochetes was statistically indistinguishable from detection of RST1 and RST3 infections. These findings demonstrate that diagnosis by C 6 ELISA remains effective for infection with all B. burgdorferi genotypes, including those with incomplete lp28-1 plasmids.The clinical progression of Lyme disease, a tick-borne illness that is caused by the spirochete Borrelia burgdorferi, is divided into early localized, early disseminated, and late stages. During the early localized phase, the disease usually manifests by a characteristic skin lesion, erythema migrans (EM). Several days or weeks later, the spirochetes may spread hematogenously and patients may develop early disseminated disease with dermatologic, cardiac, neurologic, and/or rheumatologic involvement. During the early disseminated phase, some patients exhibit dermatologic signs that appear as multiple EM (24,27,29,33). Late disease presents mainly with arthritis or neurologic manifestations (28).Evidence has been put forward to suggest that a major determinant of the risk of B. burgdorferi dissemination in Lyme disease patients with EM is the genotype of the infecting spirochetal strain. Three genotypes have been identified on the basis of restriction fragment length polymorphisms in the rRNA spacer region and have been designated RST1, -2, and -3 (16). Patients infected with RST1 spirochetes had the highest proportion of blood culture positivity (43%), those infected with RST2 spirochetes were intermediate (20%), and those with RST3 had the lowest proportion (3%). In general, persons with an RST1 infection had more symptoms and symptoms of greater severity than those with either RST2 or RST3 infection (32). Mice that were inoculated with RST1 organisms were significantly more likely to yield cultivable spirochetes from different organs and showed a significantly higher prevalence of both carditis and arthritis than did animals inoculated with RST3 spirochetes (30); RST2 isolates were not assessed. When the plasmid contents of the different human infectious type...

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A Decrease in the Immunoglobulin G Antibody Response against the VlsE Protein of Borrelia burgdorferi Sensu Lato Correlates with the Resolution of Clinical Signs in Antibiotic-Treated Patients with Early Lyme Disease

Cited by 24 publications

References 43 publications

Evaluation of the Recombinant VlsE-Based Liaison Chemiluminescence Immunoassay for Detection ofBorrelia burgdorferiand Diagnosis of Lyme Disease

Evaluation of the Recombinant VlsE-Based Liaison Chemiluminescence Immunoassay for Detection ofBorrelia burgdorferiand Diagnosis of Lyme Disease

Comparison of an automated Borrelia indirect chemiluminescent immunoassay (CLIA) with a VlsE/C6 ELISA and Immunoblot

Borrelia burgdorferi Spirochetes That Harbor Only a Portion of the lp28-1 Plasmid Elicit Antibody Responses Detectable with the C ₆ Test for Lyme Disease

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A Decrease in the Immunoglobulin G Antibody Response against the VlsE Protein of Borrelia burgdorferi Sensu Lato Correlates with the Resolution of Clinical Signs in Antibiotic-Treated Patients with Early Lyme Disease

Cited by 24 publications

References 43 publications

Evaluation of the Recombinant VlsE-Based Liaison Chemiluminescence Immunoassay for Detection ofBorrelia burgdorferiand Diagnosis of Lyme Disease

Evaluation of the Recombinant VlsE-Based Liaison Chemiluminescence Immunoassay for Detection ofBorrelia burgdorferiand Diagnosis of Lyme Disease

Comparison of an automated Borrelia indirect chemiluminescent immunoassay (CLIA) with a VlsE/C6 ELISA and Immunoblot

Borrelia burgdorferi Spirochetes That Harbor Only a Portion of the lp28-1 Plasmid Elicit Antibody Responses Detectable with the C 6 Test for Lyme Disease

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Borrelia burgdorferi Spirochetes That Harbor Only a Portion of the lp28-1 Plasmid Elicit Antibody Responses Detectable with the C ₆ Test for Lyme Disease