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Monday, November 7, 2016

Lyme disease tests: New and Old

Diagnostic testing

Testing may be difficult when the standard diagnostic test fails. The gold standard, the identification of the organism by DNA or culture is frequently not feasible or available. Several antibody tests have been developed which may be helpful, but these tests have a low sensitivity, missing many cases. As an adjunct, a newer technology involves lymphocyte stimulation.  When cells (T lymphocytes) are exposed to proteins derived from the pathogen, cell mediated responses such as the release of gamma interferon can be measured indicating prior exposure to the pathogen. This test may have limitations and likely should only be used adjunctively.
Of course, we are talking about diagnostic procedures for Mycobacterium (tuberculosis).
Let’s talk about Lyme.

Testing for Lyme remains problematic.  Tests have been inaccurate, unreliable and at times and prohibitively expensive. 
We depend on clinical diagnosis. But sometimes we are not sure.
All currently available tests have pros and cons.
A lot of labs are suddenly getting into the Lyme testing business.  Many tests are in development.
The Western Blot remains the first line test.  It is important that a Western Blot be ordered, not just an ELISA with reflex to Western Blot. The ELISA is not dependable. An alternative ELISA, the C6 peptide may be ordered. Usually negative, sometimes it is positive when other tests are not.   A C6 from LabCorp/Quest is not adequate, a numerical value, available from various reference laboratories is needed. (MDL, IgeneX, many others).  In my experience, values under the lab recommended positive cutoff may indicate exposure to Lyme.
PCR (polymerase chain reaction) is a test which measures the presence of specific DNA.  Most consider this the gold standard.  DNA testing for Lyme also has a low sensitivity and misses most cases. The only specimen available to test is usually blood. Lyme is a tissue pathogen and may be present in the blood in very small numbers. This is different from viral illnesses such as HIV and Hepatitis C where large numbers of viral particles are present in the blood.  Many clinical labs are working on ways to improve the sensitivity of the test.  Urine may be a better place to look.  Lyme lives in the bladder and is shed in urine. One such test is offered by Quest. So far I have not found any positives. Other clinical labs may have better results.
This is not to be confused with the antigen capture test or the nanotechnology test, which also looks at urine samples.
The Nanotrap captures tiny amounts of proteins found on the surface of the Lyme bacteria. The test so far only measures outer surface protein A, or OspA.  This protein corresponds with the 31 band of the Western Blot.  Remember, Lyme is a clever “shape shifter.” This protein is expressed when the spirochete is attached to the gut of the tick. After infection, this protein disappears (downregulated) and Osp C (upregulated) takes its place. So, the current test is really only helpful for acute Lyme and -- maybe late-stage Lyme. After many months of infection, this protein (OspA) may reappear. The test as it sits is not clinically useful for most patients.
The scientists at the Center for Applied Proteonomics and Molecular Medicine, George Mason University, new to the field, were shocked that the so-called experts in the field insisted that chronic Lyme is not real.  To get "proof of concept" and the blessing of the IDSA, ILADS and the CDC, the new test was designed to detect only acute Lyme. The CDC admits that current testing (two tier test) for acute Lyme is flawed, and THERE IS AN X-PRIZE award for the first lab to develop an accurate acute Lyme test!  
Now there is general proof of concept. An improved test, said to come out soon, will look for many proteins, including OspC.   The improved test may be extremely helpful for the diagnosis of all stages of Lyme disease.  
A culture test from ALS is available. After being slammed by the CDC, the lab is actively engaged in studies to achieve FDA clearance.  The blood culture test has two drawbacks: cost and the patient must be off antibiotics for 2 months before the test is performed. Otherwise, it may be a very good test. At first I was concerned that the test found Borrelia species rather than B. burgdorferi. This may be an advantage rather than a disadvantage because Lyme disease is a borreliosis comprised of an expanding menu of species and strains.
Another test, Lymphocyte transformation test, is available from Pharmasan and others. This test measures a different kind of immune response.  It is based on FDA approved, commercially available TB tests.  The test measures the innate immune response. An initial response which predates acquired immune responses which lead to antibody production. Immune cells patrolling our blood and tissues have the ability to recognize patterns which shouldn't be there (Pattern Recognition Receptors). Killer T cell lymphocytes are the first line of defense. Killer T cells attack offending antigen (Lyme) and turn on other immune responses including the production of cytokines, modulators of immune regulation.  When this reaction occurs it leaves behind permanent T memory cells. These memory cells, when exposed to Lyme antigens react by releasing gamma interferon, a potent cytokine.  This reaction can be measured.  This test may be considered a complement to other tests, such as the Western Blot test. It is somewhat costly.
From a cost perspective, in my experience, it is best to start with a Western Blot (MDL) which provides images and alternative diagnostic criteria.
A fair question might be: since the Western Blot only shows exposure to Lyme, not the presence of actual infection, shouldn’t a test that directly measures Lyme infection be done, to prove that Lyme is there?
Here is my answer:  Since Lyme persists in mice, dogs and monkeys and test tubes and the test subject has symptoms compatible with Lyme disease, it is reasonable to conclude active infection is present. Further testing is not needed.  Additional tests may have false negative results only adding a layer of unneeded confusion. The goal of therapy is remission of symptoms, not eradication of organisms.

At the end of the day, in many cases, the diagnosis of Lyme disease is clinical and the role of lab testing adjunctive only.


Kurt said...

Sounds like the science is advancing! One one hand we are hearing about better diagnostics in your blog post, and on the other new antibiotics are being explored for the treatment of Bb. This is great news, keep up the great work, Doc!

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Mdelia said...

Thanks once more for posting your knowledge. You did not mention DNA Connexions. Interesting test, by no means close to what we need: which is definitive testing to determine the presence of active infection; However, it is an interesting test for those with persisting symptoms perhaps indicating the presence of undiagnosed co-infections. For example this DNA PCR (if I am understanding it correctly) will show presence of exposure. Like common infections, such as chicken pox may be present in our terrain, but unexpressed, is it not possible to do this test as a means to understand the infectious load a patient is carrying, i.e. erlichhia- and through this, understand more completely how to treat. Questions, questions, again, thanks for all you share.

Unknown said...

My chiropractor internist is recommending I do the DNA Connexions (submit a urine sample for Lymes test). She had me do the Western Blot Serum and IgG P41 was present abnormal. The rest were absent. The Lyme IgG WB interpretation was Negative. My husband is freaking out about the expenses for the tests. I just want to know-do I or don't I have it. Thanks for your blog. You have my attention. Jeannie Heredia