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Specific Testing in Europe for Lyme disease

The US CDC 2T testing does not perform well in detecting European endemic Borrelia species nor European strains of Bb. It is very difficult to get the European testing done in the US. The only test readily available in the US that "might" pick up the European species and strains is the Immunetics C6 peptide. The US CDC 2T test is based on antigens derived from the US Northeast B31 strain of Bb which leads to many test failures. This is due to the species or strain having had antigenic drift from a common ancestor such that the antibodies no longer bind to the epitopes on the same surface protein/antigen epitope. The Advanced Laboratory Services culture combined with the DNA sequencing plus the C6 is the best way to pick up a CDC 2T failure due to species or strain antigenic drift. The C6 test has been vetted by Wormser and the gang and its been considered as a replacement for the CDC 2T test. I had 4/5 antibodies on the CDC 2T test which is a negative but was both C6 positive and culture positive.

All Borrelia species and strains have a common ancestor. All Borrelia species and strains share the same outer surface proteins including ErpA, RevA, DbpA - 17, OspC - 23, OspD - 28, 30, OspA - 31, OspB -34, BmpA - 39, FlaB - 41, VlsE, 45, BBK32 - 47, 58, 66 and P83/100 - 93. These are proteins that make up their outer surface. By being on their outer surface, they are accessible to antibodies. The numbers are their weights in kDa. Each of these drift in their exact molecular structure due to small DNA errors accumulating through many generations. When these errors occur in the DNA that codes for these surface proteins, small changes occur in the proteins. This change in molecular makeup includes the sites that antibodies bind called epitopes. These DNA errors accumulate and change the epitopes on these surface proteins which are critical to both immune response and antibody based testing. Antigenic drift is why its so difficult to create a universal FLU vaccine.

The CDC 2T test does not include all the specific surface proteins/antigens and was limited to 10 due to the narrow study from which it was derived. Then it requires the Bb B31 derived antibodies to bind to 5 out of the 10 chosen surface proteins. If the strain or species of an infected person has drifted its surface proteins/antigens and epitopes sufficiently away from the B31 proteins/antigens and epitopes, then the test will fail. This is why the European species ( or most others and some strains of Bb) are not detected. This is why the Europeans use tests based on local strains and typically require less than 5/10 antibodies. The US is larger than Europe and has a similarly broad set of strains and species but this has yet to be realized by US researchers since Bb is dominant but not unique.

The C6 peptide is a vary stable peptide on the invariable region on the VlsE surface protein. This means its less sensitive to this antigenic drift but not perfect. The test does not have the problem created by requiring 5/10 antibodies. By requiring 5/10 antibodies on the CDC 2T test, its made very sensitive to antigenic drift. There must be 5 surface proteins where the immunodominant epitopes are identical such that the B31 based antibodies bind. The odds are not very good since most of the surface proteins are unstable. This is one of the most significant flaws in the US CDC 2T test and led to its complete failure in Europe.

Since most of the studies in the US have been done in the Northeast and the B31 was a common Northeast strain, the studies have overestimated the test performance by failing to cover this antigenic drift of epitopes problem. The belief that there is only one species of Borrelia in the US that infects people is reinforced by the tests inability to catch other species or widely antigenically drifted Bb strains. If the tests available to doctors caught most or all strains like a culture, we would not have this dogma. I suspect if the CDC changed or added the C6 peptide test in the diagnostic protocol ( as CDC 2T or C6 = positive), many cases not previously detected would be found. This in turn would lead to the collapse of the Bb only dogma. The reason its not been changed by the CDC is the limited studies suggest it has a 1% lower specificity and equal or better sensitivity. Thats absurd since the studies are so limited making the 1% meaningless. Its like making a measurement of 3 decimal places on an instrument only capable of 2 decimal places accuracy. I believe it would be shown to have much better sensitivity if the antigenic drift problem was properly considered and far better specificity if one is looking for any Borrelia and not just Bb B31.

So that's the long way answer to how you might detect a species or strain which isn't caught by the standard CDC 2T test and why.


The Immunetics C6 test is available through Quest, StonyBrook or IGenex.


http://www.igenex.com/files/PATIENT_TES ... T_FORM.pdf

http://www.stonybrookmedicalcenter.org/ ... 20FORM.pdf


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