Unorthodox Lyme Disease Test Proposed as Follow-Up Check for Late Stage Borreliosis.

by lmatthews on November 12, 2012

lymphocyte transformation test not on CDC approved two tier testing for lyme disease

The lymphocyte transformation test is not CDC-approved for lyme disease diagnosis.

Lyme disease testing is notoriously fraught with difficulties, with early antibody tests failing to pick up infection and later tests finding residual antibodies despite infection being eradicated. However, a new test for Lyme disease, the lymphocyte transformation test (LTT) has been proposed as a way to verify the efficacy of antibiotic treatment and new research suggests a high level of specificity and sensitivity for active Lyme disease. The Centers for Disease Control (CDC) continues to warn against such unapproved tests, as has the UK Health Protection Agency (HPA) in recent weeks, but will new evidence change official guidelines?

Available Lyme Disease Tests

Publishing their work in The Open Neurology Journal, von Baehr, et al, reported last month on the use of LTT to detect Borrelia afzelii, Borrelia garinii and Borrelia burgdorferi sensu stricto. One of the difficulties with ELISA tests and Western Blots for Lyme disease is the limited strains of Borrelia included in the antibody testing, causing problems for those infected overseas or with a variant strain. Whilst LTT is unable to detect significantly mutated forms of the Lyme disease bacteria it does appear to be effective at identifying active infection with the three most common strains found in the US, Europe and Asia.

Current Lyme Disease Testing Problems

In most cases of Lyme disease, antibodies are not able to be detected for several weeks after the tick bite and infection. Even when antibodies are detected it may be that the patient has no active infection but neither an ELISA test nor a Western Blot can determine this with accuracy. Polymerase chain reaction (PCR) testing for Lyme disease is not sensitive enough to diagnose or exclude borreliosis alone and so these researchers looked at the use of a lymphocyte transformation test using lysate antigens to assess sensitivity.

Use of LTT in Early Stage Lyme Disease


The new Lyme disease test uses recombinant OspC and was developed by investigating test sensitivity for seronegative and seropositive healthy individuals and those with clinical signs of borreliosis and seropositivity. According to the newly published data the LTT had an 89.4% sensitivity rate for clinical borreliosis prior to antibiotic treatment, with specificity of 98.7%. Comparing the results of usual serological tests for Lyme disease with LTT, 79.8% of the 1480 patients assessed had similar results. Seropositive individuals who had a negative result on LTT accounted for another 18%, many of whom had been tested after antibiotic therapy.

Monitoring Recovery from Lyme Disease

The remaining 2.2% had a positive LTT and negative serology and half of these had early erythema migrans, perhaps demonstrating the use of LTT in detecting cases of Lyme disease before standard testing methods are able to do so. After antibiotic treatment, the results on LTT were borderline or negative for those patients who had early symptoms of Lyme disease. Those with late stage Lyme disease symptoms remained positive on LTT but with signs of regression of disease activity, thus the researchers consider LTT a useful tool for monitoring treatment of disseminated Borrelia infection.

Concerns About LTT for Lyme Disease

The lymphocyte transformation test is one of many tests deemed unorthodox and unapproved by the CDC and the UK HPA. This latest research took such concerns into account and, indeed, was aimed in part at addressing such concerns. They specifically note in the paper that false positives have been described in the literature and that the apparent decline in positive LTT reactions of blood lymphocytes to Lyme disease antigens after antibiotic treatment provided the motivation for the research. The researchers emphasize their focus on using improved cell culture and measurement techniques to combat problems with previous research into LTT. The hypothesis tested in this study was that it is only during an active immune response to Borrelia infection that Borrelia-specific T helper cells circulate, and that the Borrelia-LTT may be helpful in detecting reduced levels four weeks after the end of antibiotic treatment, indicating eradication of the infection.

Previous problems with the use of LTT were, according to the authors, largely due to methodology and it was their intention with this research to find ways to overcome such difficulties, including by using interferon-α in the cell culture medium to inhibit nonspecific proliferation of lymphocytes, promote the function of antigen-presenting cells and thus aid discrimination between positive and negative test results.

Future Use of LTT for Lyme Disease

This Lyme disease test could, therefore, be helpful for patients with continuing symptoms of Lyme disease after antibiotic treatment. By demonstrating a reduction in the activity of infection it may be that their physician begins to consider differential diagnoses for Lyme disease and that patients with multiple health issues access earlier and more effective treatment for unrelated conditions that may appear similar to borreliosis. This much maligned Lyme disease test, the lymphocyte transformation test, has not yet been approved for use in the US; hopefully, further studies will bear out its efficacy.

Reference


Volker von Baehr, Cornelia Doebis, Hans-Dieter Volk, Rüdiger von Baehr, The Lymphocyte Transformation Test for Borrelia Detects Active Lyme Borreliosis and Verifies Effective Antibiotic Treatment, The Open Neurology Journal, 05 October, 2012; 6: Pp. 104-112.


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