Lyme disease is caused by the spiral-shaped bacterium, Borrelia burgdorferi, transmitted to humans through the bite of infected blacklegged ticks. Diagnosis relies on a two-tiered testing protocol, beginning with a screening test, typically an Enzyme-Linked Immunosorbent Assay (ELISA). If the ELISA is positive or borderline, a confirmatory Western Blot test is performed. A “false positive” occurs when a blood test indicates antibodies to Borrelia burgdorferi, but the individual has never been infected. This error arises because the assay detects the body’s immune response, not the pathogen itself, which introduces the possibility of error.
The Biological Basis: Cross-Reactivity
Lyme disease tests are indirect, searching for specific antibodies the immune system creates in response to the Borrelia bacteria. These antibodies are proteins called immunoglobulins. The challenge arises because the proteins on the surface of Borrelia burgdorferi, known as antigens, can structurally resemble proteins found on other microorganisms or human cells.
This phenomenon is called antigenic similarity or cross-reactivity, and it is the primary reason a test result can be misleading. When the body mounts an immune response against a different microbe, the resulting antibodies may mistakenly bind to the Borrelia antigens used in the test kit. This non-specific binding triggers a positive reading even when the person is not infected with Lyme disease.
The initial screening ELISA is particularly susceptible to these cross-reactions, which is why it must be followed by the more specific Western Blot. However, even the Western Blot, especially the IgM portion which detects early antibodies, can yield false positive results. The potential for cross-reactivity means a positive antibody test must always be carefully interpreted alongside a patient’s clinical symptoms and history of tick exposure.
Specific Pathogens That Mimic Lyme
Several infectious agents cause cross-reactive antibodies that lead to false positive Lyme tests. The most common culprits are other spirochetes, which are bacteria that share the same characteristic spiral shape as the Lyme bacterium. Syphilis, caused by the spirochete Treponema pallidum, often produces antibodies that react with the Borrelia antigens in a Lyme assay, particularly due to shared flagellar proteins.
Similarly, other species of Borrelia that cause relapsing fever, such as Borrelia hermsii or Borrelia miyamotoi, are closely related to the Lyme agent. Antibodies generated against these relapsing fever bacteria frequently cross-react with the antigens used in standard Lyme serological tests.
Beyond spirochetes, certain viral infections also provoke an immune response that interferes with Lyme testing. Both infectious mononucleosis (Epstein-Barr Virus) and Cytomegalovirus (CMV) infections can generate antibodies that cross-react with Borrelia proteins. Even common bacterial infections like Helicobacter pylori have been associated with producing non-specific antibodies that may confuse a Lyme test result. These infections demonstrate how a robust immune response to a completely different pathogen can lead to an inaccurate Lyme diagnosis.
Autoimmune Conditions and Testing Variables
False positive Lyme results are not solely caused by infectious diseases, as certain non-infectious, chronic conditions can also trigger misleading results. Autoimmune disorders, where the immune system mistakenly attacks its own tissues, often generate a wide variety of non-specific antibodies. Conditions like Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA), and Sjögren’s syndrome can produce autoantibodies that nonspecifically bind to Borrelia antigens on the test.
The resulting high levels of these circulating antibodies can interfere with the sensitivity and specificity of the laboratory assay, leading to a positive reading. For instance, patients with SLE often produce anti-nuclear antibodies (ANA) that can skew the results of the initial ELISA screen. This is a significant consideration, as the symptoms of many autoimmune diseases, such as joint pain and fatigue, overlap with the symptoms of chronic Lyme disease.
In addition to biological cross-reactivity, technical factors also contribute to false positives. The use of a now-discontinued recombinant Outer Surface Protein A (OspA) Lyme vaccine, known as Lymerix, caused a lasting antibody response that can still trigger a positive test years later. Furthermore, the interpretation of the Western Blot is subjective; variations in laboratory protocols or kit components can sometimes lead to an incorrect positive interpretation. False positive IgM results are a particular concern, often classified as false if a follow-up IgG test remains negative after several months.