Blood Tests for Lyme Disease
Laboratory Diagnosis of Lyme Disease (B. burgdorferi) Infection
Lyme disease is the most common tick-borne illness in the United States. It is a complex multi-system disease caused by infection of Borrelia burgdorferi bacteria and transmitted by the bite of the deer tick. This infection elicits a series of predictable host immune responses which provide the basis for current blood tests, the principle laboratory method for documenting Lyme infection.
The most commonly used tests are relatively insensitive in the very early stages of infection. The traditional western blot test improves the specificity of the diagnosis during later stages of infection, but it too may lack both sensitivity and specificity in early infection.
Clinicians are frequently confronted with patients presenting with unexplained illnesses, fevers, rashes, swollen joints, or neurologic symptoms (such as cranial nerve palsies or suspected meningitis). There are also challenging patients with persistent nonspecific symptoms after being treated for well-documented Lyme disease, and patients who develop new symptoms raising the suspicion for re-infection. The combination of antibody capture EIA and immunoblotting (WB) in most cases can assist the clinician in assessing these situations and lead to the correct diagnosis.
Early Lyme disease;
If presenting with classic features (EM rash) in an endemic area, is diagnosed straightforwardly. Diagnosis is more challenging, however, if symptoms are not typical and laboratory testing is indicated. Most patients (~90%) symptomatic with B. burgdorferi infection are sero-positive (blood testing), demonstrating an initial IgM response best shown by antibody capture. If a patient is suspected of having early Lyme disease is initially sero-negative, repeat follow-up testing is very useful. The evolution of the host immune response to B. burgdorferi infection is typically very quick. In as short a time as a week or two, an initially seronegative patient can develop robust seropositivity. Unlike the IgM and IgG response (which may persist), IgA levels usually fall rapidly with effective treatment and infection resolution, often becoming undetectable within the first few months. In that early “window” of an infection, when a patient is sometimes acutely symptomatic, but prior to developing a detectable serologic response, it is possible with PCR technology to detect the DNA of B. burgdorferi in a whole blood specimen.
Late Lyme disease;
May present with various neurological or musculoskeletal symptoms, and lacks truly pathogenic features. In these situations, laboratory confirmation of infection provides the clinician with invaluable assistance. By late in the infection, significant levels of IgG specific antibodies are easily detectable by both antibody capture EIA and immunoblotting (WB). IgM and IgA are variably present in late untreated patients. n.
No evidence of Lyme disease;
A “negative” test, is manifested by the absence of significant laboratory findings by antibody capture EIA and by IgG immunoblotting (WB). It is not uncommon to observe reactivity to a few antigens (bands) by immunoblots, reflecting past exposure to other microbial infections. This faint cross-reactivity does not constitute serologic evidence of Lyme disease. Similarly, a borderline or low level of IgM response, as the sole laboratory finding, in patients with chronic symptoms (4-6 weeks or longer) does not constitute evidence of recent or active Lyme infection as an explanation of a patient’s symptoms. This finding is often due to cross-reactive antibodies induced by another infection or condition (e.g. EBV, VZV, syphilis, dermatomyositis).
IMUGEN;
Offers a comprehensive Lyme Antibody Analysis which includes IgM, IgG, and IgA antibody capture EIA, IgG immunoblotting (WB) on 2 strains of B. burgdorferi, and PCR testing on SF, CSF, and whole blood.
The staff at IMUGEN is highly trained in performing and interpreting these assays, has decades of experience in analyzing these test results in the context of various clinical situations, and is available to assist healthcare providers in interpreting tests and answering questions about the diagnosis of tick-borne infections.
Courtesy: http://imugen.com/education/lyme.html
Imugen is a Clinical Laboratory located in Norwood, MA specializing in clinical blood test for Lyme disease handling specimens for the tick-borne diseases. The Lyme disease vaccine is currently available throughout the different ELISA testing. From working with different physicians and trials, Imugen can clearly identify true infection from vaccination. Current ELISA testing will simply provide a false positive result, further complicating the physicians ability to truly treat an infected patient and therefore creating larger downstream costs to an already burdened healthcare system. With the availability of the Lyme vaccine, which confounds current ELISA testing, the strength of IMUGEN testing becomes even clearer. IMUGEN has worked during vaccine trials with numerous physicians and can clearly identify true infection from vaccination.
The clinical validity;
The most common blood tests for Lyme disease are insensitive in the very beginning stages of the infection. During later stages of infection, the traditional western blot test improves the specificity of the diagnosis , but it too may lack both sensitivity and specificity in early infection. The clinical value of these tests depends upon both inherent lab test performance characteristics, as well as, the pre-test likelihood of disease in the population being tested. Screening asymptomatic or non-specifically symptomatic individuals in whom the probability of Lyme disease is low (such as patients with chronic fatigue, headaches, depression, or back pain) is not recommended. A positive test result in such patients, even in a highly endemic area, may not significantly increase the post-test probability that these patients have Lyme disease. To address the performance limitations of routine testing, a combination of both Antibody Capture EIA and Immunoblotting (WB) with clinically relevant interpretations is offered by IMUGEN to provide more useful information to clinicians. IgM, IgG, and IgA antibody capture EIA results combined with immunoblotting (WB) detects a wider array of host immune responses to B. burgdorferi infection. Furthermore, IMUGEN utilizes two different strains of B. burgdorferi for immunoblotting (WB). One is a wild strain isolated from a North American patient with Lyme disease, and one is a tick isolate mutant strain lacking the gene for the B. burgdorferi OspA protein. This is essential in evaluating patients suspected of having Lyme disease who may have received past Lyme vaccine. There are also challenging patients with persistent nonspecific symptoms after being treated for well-documented Lyme disease and patients who develop new symptoms raising the suspicion for re-infection. The combination of antibody capture EIA and immunoblotting (WB) in most cases can assist the clinician in assessing these situations and lead to the correct diagnosis.
Early Stages of Lyme Disease
If presenting with classic features (EM rash) in an endemic area, is diagnosed straightforwardly. Diagnosis is more challenging however if symptoms are not typical, and laboratory testing is indicated. Most patients (~90%) symptomatic with B. burgdorferi infection are sero-positive (positive blood test), demonstrating an initial IgM response best shown by antibody capture EIA. If a patient is suspected of having early Lyme disease is initially sero-negative, repeat follow-up testing is very useful. The evolution of the host immune response to B. burgdorferi infection is typically very quick. In as short a time as a week or two, an initially seronegative patient can develop robust seropositivity. The IgA response on antibody capture EIA is noted in early infection as well. Unlike the IgM and IgG response (which may persist), IgA levels usually fall rapidly with effective treatment and infection resolution, often becoming undetectable within the first few months. In that early “window” of an infection, when a patient is sometimes acutely symptomatic but prior to developing a detectable serologic response, it is possible with PCR technology to detect the DNA of B. burgdorferi in a whole blood specimen. It has been our observation that this window of B. burgdorferi bacteremia is brief, and by the time the patient has developed the characteristic serologic response, whole blood PCR testing for Lyme will have become negative.
Late Stage Lyme Disease Treatment
May present with various neurological or musculoskeletal symptoms, and lacks truly pathogenic features. Late in the infection, significant levels of IgG specific antibodies are easily detectable by both antibody capture EIA and immunoblotting (WB). IgM and IgA are variably present in late untreated patients. The serologic characteristics are usually different for most patients with late stage infection. In addition to serologic testing, bacterial DNA may be detected, especially in the bodily fluids of patients with Lyme, and rarely if ever in whole blood late in the infection.