Tuesday, July 15, 2008
Lyme antibodies revisited
The ELISA test for Lyme is a good test. The problem is that the cutoff for a positive reaction is set too high. This technology is very good. In this test an enzymatic reaction causes a color change when antibodies react with antigens(Lyme proteins). The amount of color change is transposed into an index. The cutoff point for a positive ELISA was set high when it was discovered that nearly everyone reacted to Lyme on the assay. It was assumed that false positives were occurring. The set point for a positive reaction was decided by a committee in a somewhat arbitrary fashion, who at the time assumed that Lyme disease was rare. Some Lyme antibodies are non-specific and cross reactive. Still the ELISA was supposed to allow for false positives which could be sorted out with the Western Blot test. Positivity of the Western Blot was also arbitrarily set based on X number of bands being positive. This makes no sense. Non-specific bands should be excluded. Bands which specifically react to outer surface proteins of Borrelia burdorferi should be sufficient to make the diagnosis even if only one band is present. Bands 23, 31, 34, 39 and 93 are so specific that a reaction to any of these bands should be considered a positive Lyme test. Indeterminate bands, especially when they occur on several of these specific locations should also suggest a positive test for Lyme. This brings us to the C6 peptide test. This is an ELISA test which correlates with specific reactivity of a very, very specific outer surface protein on the Lyme bacteria. There are virtually no false positives here. The cutoff has been set so high that the test is worthless based on the standards set by the manufacturer. It is interesting that Gary Wormser, the chief critic of chronic Lyme is financially connected to Immunetics, the company which developed this test. There is no reason for any non zero value other than exposure of the immune system to the spirochetes which cause Lyme disease. In fact C6 peptide indices of 0.2 to 0.3 are typically seen in patients who have positive Western Blots even by CDC surveillance criteria. Patients who are treated for Lyme frequently sero-convert. They develop a greater antibody response after antibiotic therapy. By the same token, the C6 peptide index frequently doubles after the patient receives therapy with antibiotics. The standard of a C6 index of greater than 0.9 is ridiculous in my experience. Any level greater that zero is suggestive. Values greater that 0.3 are reliable in confirming the diagnosis. To date there are no published studies comparing C6 index levels to Western Blot positivity. When this data is published it will turn out that C6 peptide index for Lyme disease will be very useful. Is often said we need a better Lyme test. We actually have a better test, we just need to learn how to interpret the results in a meaningful way.