Tests for Lyme disease usually give results in terms of negative, positive, or borderline, but these decisions are made based on the antibody titer of the test. Serological tests, such as ELISA, Western blot, and IFA, use a sample taken from the patient that usually consists of blood, cerebrospinal fluid, or even synovial fluid in some cases. This sample is then challenged with known antigens (Borrelia bacteria in the case of Lyme disease) to detect the presence of antibodies to these antigens. A titer is a measure of how much a sample can be diluted before antibodies are no longer able to be detected.
Titers are usually expressed as ratios such as 1:256, meaning that one part serum to 256 parts saline solution (dilutant) results in no antibodies remaining detectable in the sample. A titer of 1:8 is, therefore, an indication of lower numbers of Lyme disease antibodies than a 1:128 titer. Where a positive IFA test result is given this means that at least a 1:256 titer was achieved, a similar result is needed on an ELISA test for Borrelia burgdorferi antibodies.
What Do Titers Really Mean?
Many people are concerned over the interpretation of such tests however as a high titer does not necessarily mean that a person is infected, nor does a low titer necessarily mean that they have either a low-grade infection or none at all. Antibody tests such as these detect only free antibodies in the sample, and those already complexed with an antigen are not detected. As such, patients with a high number of antigen-antobody complexes may have a significant infection but this will not be borne out by testing if there are few free antibodies in their serum sample.
A low titer may in fact demonstrate significant success on the part of the immune system in fighting off an infection with Lyme disease bacteria, whereas a high titer could show residual antibodies to a previous infection, or unsuccessful attempts to bond to the antigens in the bloodstream by the antibodies. The decision by the CDC and other agencies to standardize the reporting of test results to positive, borderline, or negative may be a disservice to patients who are told that they do not have Lyme disease on the basis of such a test. Conversely, where a high titer is found but the patient is not symptomatic it is inappropriate to treat them with antibiotics as there may no longer be an active infection.
Antibody Levels at Different Stages of Lyme Disease
Antibodies to Borrelia bacteria may take up to two months to reach peak levels, with immunoglobulin M appearing between two and four weeks after infection, and immunoglobulin G taking between four and six weeks to reach detectable levels in most cases. Early testing for Lyme disease is likely to return a negative result therefore, as antibody levels are not sufficient to meet the 1:256 cut-off for positivity. Ensuring that the correct testing, either for IgM, IgG, or both, is carried out at the appropriate time is also important so as not to invalidate the purpose of the test.
In some cases a positive result on an antibody test may be false due to potential cross-over reactions for antibodies to other bacteria, such as syphilis, or viruses, such as Epstein-Barr or human immunodeficiency virus (HIV). An autoimmune response in the body may also confound the results as antibodies to the patient’s own tissues may be detected in conditions such as Lupus or Rheumatoid Arthritis. Two-tier testing with Western blot is recommended in an attempt to clarify the clinical situation where a high, or borderline Lyme disease titer result is given as this is not sufficient evidence on its own of current infection with Lyme disease.