VlsE C6 peptide and IgG ELISA antibody analysis for clinical diagnosis of Lyme borreliosis in an endemic area

Nyman, Dag; Willen, Laure; Jansson, Christian; Carlsson, Sten-Anders; Granlund, Helena; Wahlberg, Peter

doi:10.1111/j.1469-0691.2006.01374.x

Cited by 21 publications

(13 citation statements)

References 2 publications

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“…The C6 assay has become the assay of choice both in the United States and Europe, either alone (3,6,8,9,14,17) or in combination with other assays (1,4,12). Sensitivity of this assay in Europe varies between 91% in a study in The Netherlands against a panel of sera from clinically defined Lyme patients confirmed by immunoblotting (16) and 33% in Italy against a panel of sera from clinically defined Lyme patients with EM confirmed by culture (10).…”

Section: Discussionmentioning

confidence: 99%

Epitope Length, Genospecies Dependency, and Serum Panel Effect in the IR6 Enzyme-Linked Immunosorbent Assay for Detection of Antibodies toBorrelia burgdorferi

Gomes-Solecki

Meirelles

Glass

et al. 2007

Clin Vaccine Immunol

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In the absence of erythema migrans, the basis for diagnosis of Lyme disease is the demonstration of an antibody response against Borrelia burgdorferi in an appropriate clinical setting. The C6 enzyme-linked immunosorbent assay, based on the IR6 region of VlsE, has become widely used in both the United States and Europe. We mapped the antigenic epitopes of IR6 to a shorter sequence that is equivalent in sensitivity and specificity to the full-length IR6 25-residue peptide. In addition, we observed significant differences in sensitivity between serum panels (60 to 100%), indicating that the selection of the serum panels can shape the apparent overall sensitivity of the assay. Contrary to prior reports, the assay sensitivity is greater when the IR6 peptide is derived from the sequence of the same infecting Borrelia genospecies. Using our North American panels and the two panels obtained from European Lyme disease patients, we determined that the IR6 assay that is based on a single genospecies of Borrelia spp. is not optimal for use as a universal diagnostic assay for Lyme disease.

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Section: Discussionmentioning

confidence: 99%

Epitope Length, Genospecies Dependency, and Serum Panel Effect in the IR6 Enzyme-Linked Immunosorbent Assay for Detection of Antibodies toBorrelia burgdorferi

Gomes-Solecki

Meirelles

Glass

et al. 2007

Clin Vaccine Immunol

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“…Antigen can sometimes be detected in urine and cerebrospinal fluid, but these tests are neither reliable nor recommended (45). Two of the most commonly used tests for diagnosis in North America are (i) the twotier test, which includes an enzyme-linked immunosorbent assay (ELISA) and Western blotting using antigen derived from wholecell lysates, and (ii) the C6 test, which detects antibodies to a specific peptide within a conserved region of the B. burgdorferi antigen VlsE (5,30,32). The C6 test has also been used experimentally for evaluation of treatment efficacy (36,37).…”

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confidence: 99%

Dynamic Longitudinal Antibody Responses during Borrelia burgdorferi Infection and Antibiotic Treatment of Rhesus Macaques

Embers

Hasenkampf

Jacobs

et al. 2012

Clin. Vaccine Immunol.

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ABSTRACTInfection withBorrelia burgdorferielicits robust yet disparate antibody responses in infected individuals. A longitudinal assessment of antibody responses to multiple diagnostic antigens following experimental infection and treatment has not previously been reported. Our goal was to identify a combination of antigens that could indicate infection at all phases of disease and response to antibiotic treatment. Because the rhesus macaque recapitulates the hallmark signs and disease course of human Lyme disease, we examined the specific antibody responses to multiple antigens ofB. burgdorferifollowing infection of macaques. Five macaques infected with strain B31 and 12 macaques infected with strain JD1 were included in the analysis. Approximately half of these animals were treated with antibiotics at 4 to 6 months postinoculation. Antibody responses to severalB. burgdorferirecombinant antigens, including OspC, DbpA, BBK32, OspA, and OppA-2, were measured at multiple points throughout infection. We have previously shown a decline in the response to the C6 peptide following antibiotic treatment. Responses to OspA and OspC, however, were variable over time among individuals, irrespective of antibiotic treatment. Not every individual responded to BBK32, but anti-DbpA IgG levels were uniformly high and remained elevated for all animals. All responded to OppA-2, with a decline posttreatment that was slow and incomplete. This is the first demonstration ofB. burgdorferiOppA-2 antigenicity in nonhuman primates. The combination of DbpA, OspC, OspA, and OppA-2 with the C6 diagnostic peptide has the potential to detect infection throughout all disease phases.

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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.…”

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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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VlsE C6 peptide and IgG ELISA antibody analysis for clinical diagnosis of Lyme borreliosis in an endemic area

Cited by 21 publications

References 2 publications

Epitope Length, Genospecies Dependency, and Serum Panel Effect in the IR6 Enzyme-Linked Immunosorbent Assay for Detection of Antibodies toBorrelia burgdorferi

Epitope Length, Genospecies Dependency, and Serum Panel Effect in the IR6 Enzyme-Linked Immunosorbent Assay for Detection of Antibodies toBorrelia burgdorferi

Dynamic Longitudinal Antibody Responses during Borrelia burgdorferi Infection and Antibiotic Treatment of Rhesus Macaques

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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VlsE C6 peptide and IgG ELISA antibody analysis for clinical diagnosis of Lyme borreliosis in an endemic area

Cited by 21 publications

References 2 publications

Epitope Length, Genospecies Dependency, and Serum Panel Effect in the IR6 Enzyme-Linked Immunosorbent Assay for Detection of Antibodies toBorrelia burgdorferi

Epitope Length, Genospecies Dependency, and Serum Panel Effect in the IR6 Enzyme-Linked Immunosorbent Assay for Detection of Antibodies toBorrelia burgdorferi

Dynamic Longitudinal Antibody Responses during Borrelia burgdorferi Infection and Antibiotic Treatment of Rhesus Macaques

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