Dr James Schaller
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The C6 Lyme Peptide ELISA

A new Lyme disease test is called the C6 Lyme Peptide ELISA.

While it is also an antibody test, which assumes the antibody system is working well, is has unique aspects.

Lyme has the ability to have many forms and strains. It has ability to hide from the immune system. This test detects antibodies to a newly discovered consistent protein on every known strain of the Lyme disease bacteria.

According to the manufacturer and some researchers, Lyme is able to evade immune system response by many means, including varying its coat seen by our immune system. Much like wearing a different coat in the winter to escape detection after robbing a bank—this allows it "variation."

How often does this change in the Lyme coat happen? One study notes Lyme varies its coat or other key proteins on certain days. The clock for coat changes starts after infection in mammals after initial infection on days 4,7,14,21,28, and 7 and 12 months post infection of mammalian hosts. (Zhang, Norris—abstract below)

According to the maker, scientists have found a part of the Lyme "coat" that does not appear to change. Specifically, "6 surface proteins" on Lyme remain constant. Scientists call these "invariable regions" (IR), which are termed IR1-6. One IR, IR6 is found in all Lyme strains. The new test is abbreviated, C6 LPE, and detects antibodies to the IR6 in infected patients.

The maker of the test reports: "diagnosis of Lyme disease has been hampered by tests that have not been standardized, are not reproducible, and are neither sensitive nor specific for this often difficult to diagnose tick-borne disease. The recent Lyme disease vaccine, which has been given to thousands of people over the past year, makes current tests for Lyme disease virtually useless. The C6 LPE has several features that ensure its accuracy and reproducibility in a wide range of patients."

BBI Clinical Laboratories, the maker of this lab test, says this new test is useful for:

  1. Patients that have received the Lyme disease vaccine.
  2. The ability to detect antibodies to all US and European strains.
  3. Patients with autoimmune diseases (e.g. non-Lyme arthritis, lupus erythematosis), other spirochete diseases (syphilis, relapsing fever), neurologic conditions, and infectious diseases. Because the C6 LPE is highly specific, people with autoimmune diseases do not yield false positive results as they often do with current Lyme tests.
  4. Since IR6 antibodies begin to be produced in early infection and are produced throughout the course of infection, the C6LPE is more sensitive for diagnosing all stages of Lyme disease, including those patients with late stage Lyme disease.

Critique and Concerns by Some Clinicians.

Some researchers feel this is a useful contribution to the lab options for testing for Lyme. It is moving through the FDA approval process reasonably as far as I can tell.

Currently, the junk way of testing for Lyme is to check a general titer and the check for the Western Blot "bands." This is called the "two-tiered" approach. While this is a poor system, it is at least occasionally useful, and can allow doctors to think through the values. Meaning, if the clinical picture makes Lyme likely and the tests are marginal, some doctors would feel Lyme is likely positive and treat. If it replaces the other tests, we are back to the simplistic basic approach to Lyme. "Oh, one test will answer all our questions."

One scientist he is not so sure it will pick up late stage patients. I do not know if this is correct.

Other's doubt that the antibody levels will remain constantly high and measurable for months and years.

If it is done, especially as the only test, if it comes back negative, even if the patient has Lyme rashes all over them, it will be hard to get any insurance company to pay for treatment. They will merely say, "Hey, the C6 Elisa test is negative so we reject your care."

Just some thoughts for you.

Best!

Dr. J


Infect Immun. 1998 Aug;66(8):3689-97.

Erratum in: Infect Immun 1999 Jan;67(1):468.

Kinetics and in vivo induction of genetic variation of vlsE in Borrelia burgdorferi.

Zhang JR, Norris SJ.

Department of Pathology and Laboratory Medicine and Department of Microbiology and Molecular Genetics, University of Texas Medical School at Houston, Houston, Texas 77030, USA.

The Lyme disease agent, Borrelia burgdorferi, is able to persistently infect humans and animals for months or years in the presence of an active immune response. It is not known how the organisms survive immune attack in the mammalian host. vlsE, a gene localized near one end of linear plasmid lp28-1 and encoding a surface-exposed lipoprotein in B. burgdorferi B31, was shown recently to undergo extensive genetic and antigenic variation within 28 days of initial infection in C3H/HeN mice. In this study, we examined the kinetics of vlsE sequence variation in C3H/HeN mice at 4, 7, 14, 21, and 28 days and at 7 and 12 months postinfection. Sequence changes were detected by PCR amplification and sequence analysis as early as 4 days postinfection and accumulated progressively in both C3H/HeN and CB-17 severe combined immunodeficient (SCID) mice throughout the course of infection. The sequence changes were consistent with sequential recombination of segments from multiple silent vls cassette sites into the vlsE expression site. No vlsE sequence changes were detected in organisms cultured in vitro for up to 84 days. These results indicate that vlsE recombination is induced by a factor(s) present in the mammalian host, independent of adaptive immune responses. The possible inducing conditions appear to be present in various tissue sites because isolates from multiple tissues showed similar degrees of sequence variation. The rate of accumulation of predicted amino acid changes was higher in the immunologically intact C3H/HeN mice than in SCID mice, a finding consistent with immune selection of VlsE variants.

PMID: 9673250 [PubMed - indexed for MEDLINE]


Infect Immun. 1998 Aug;66(8):3698-704.

Genetic variation of the Borrelia burgdorferi gene vlsE involves cassette-specific, segmental gene conversion.

Zhang JR, Norris SJ.

Department of Pathology and Laboratory Medicine and Department of Microbiology and Molecular Genetics, University of Texas Medical School at Houston, Houston, Texas 77030, USA.

The Lyme disease spirochete Borrelia burgdorferi possesses 15 silent vls cassettes and a vls expression site (vlsE) encoding a surface-exposed lipoprotein. Segments of the silent vls cassettes have been shown to recombine with the vlsE cassette region in the mammalian host, resulting in combinatorial antigenic variation. Despite promiscuous recombination within the vlsE cassette region, the 5' and 3' coding sequences of vlsE that flank the cassette region are not subject to sequence variation during these recombination events. The segments of the silent vls cassettes recombine in the vlsE cassette region through a unidirectional process such that the sequence and organization of the silent vls loci are not affected. As a result of recombination, the previously expressed segments are replaced by incoming segments and apparently degraded. These results provide evidence for a gene conversion mechanism in VlsE antigenic variation.

PMID: 9673251 [PubMed - indexed for MEDLINE]


Cell. 1997 Apr 18;89(2):275-85.

Erratum in: Cell 1999 Feb 5;96(3):447.

Antigenic variation in Lyme disease borreliae by promiscuous recombination of VMP-like sequence cassettes.

Zhang JR, Hardham JM, Barbour AG, Norris SJ.

Department of Pathology and Laboratory Medicine, University of Texas Medical School at Houston 77030, USA.

We have identified and characterized an elaborate genetic system in the Lyme disease spirochete Borrelia burgdorferi that promotes extensive antigenic variation of a surface-exposed lipoprotein, VlsE. A 28 kb linear plasmid of B. burgdorferi B31 (lp28-1) was found to contain a vmp-like sequence (vls) locus that closely resembles the variable major protein (vmp) system for antigenic variation of relapsing fever organisms. Portions of several of the 15 nonexpressed (silent) vls cassette sequences located upstream of vlsE recombined into the central vlsE cassette region during infection of C3H/HeN mice, resulting in antigenic variation of the expressed lipoprotein. This combinatorial variation could potentially produce millions of antigenic variants in the mammalian host.

PMID: 9108482 [PubMed - indexed for MEDLINE]

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