The Rapid Plasma Reagin (RPR) test is a common blood screening tool used to detect syphilis, an infection caused by the bacterium Treponema pallidum. A reactive, or positive, RPR result suggests the presence of antibodies associated with the infection, but it does not confirm a diagnosis of syphilis. Non-syphilis-related conditions can trigger a positive result, a phenomenon known as a Biological False Positive (BFP). These false positives occur when the body produces antibodies that react with the test components, even when the Treponema pallidum bacterium is absent. Recognizing the causes of a BFP is important to prevent unnecessary anxiety and to guide subsequent, more specific diagnostic steps.
Understanding How the RPR Test Works
The RPR test is classified as a non-treponemal test, meaning it does not directly look for antibodies against the Treponema pallidum bacterium itself. Instead, it screens for “reagin,” which is a mixture of Immunoglobulin M (IgM) and Immunoglobulin G (IgG) antibodies. These antibodies are produced by the body in response to lipoidal material released from host cells that have been damaged by the syphilis infection. The test reagent contains an antigen composed of cardiolipin, cholesterol, and lecithin, which mimics the lipoidal material released during tissue damage.
When these reagin antibodies are present in a patient’s blood, they bind to the cardiolipin antigen in the test solution, causing a visible clumping, or flocculation, which is read as a reactive result. False positives occur because cardiolipin is a lipid found naturally in the membranes of human cells. Any condition that causes significant tissue or cellular damage, or a strong immune response, can stimulate the production of these same anti-cardiolipin antibodies, leading to cross-reactivity with the RPR test antigen.
Acute and Temporary Causes of a False Positive
Many cases of false-positive RPR results are acute, meaning they are transient and typically resolve within six months. These temporary false positives are often linked to a strong but short-lived immune system activation triggered by various infections or medical interventions. Recent acute viral infections are frequent culprits, including infectious mononucleosis, measles, and chickenpox.
Acute febrile illnesses, or short-term illnesses accompanied by fever, can similarly provoke non-specific antibody production. Recent vaccinations, such as those for smallpox or COVID-19, can stimulate the immune system enough to cause a temporary false positive result. Pregnancy is another common physiological state that can lead to a transient false positive RPR result due to hormonal and immunological changes.
Chronic Conditions and Autoimmune Factors
When a false positive RPR result persists for longer than six months, it is considered chronic and is frequently associated with long-term health issues. Autoimmune diseases are a major cause of persistent false positives because they involve the constant production of autoantibodies that target the body’s own tissues. Systemic Lupus Erythematosus (SLE) is a prime example, where patients produce anti-cardiolipin antibodies as part of their disease, directly causing a positive RPR test.
These chronic conditions create a state of sustained inflammation, which continuously stimulates the immune system to produce antibodies that cross-react with the RPR test’s lipid antigen. Certain chronic infections also cause persistent false positives, including Human Immunodeficiency Virus (HIV), Hepatitis C, and Lyme disease. Chronic intravenous drug use is another factor that frequently results in a persistent false-positive RPR.
Confirming or Ruling Out Syphilis
A reactive RPR result necessitates a follow-up test to definitively determine if the patient has syphilis. The next step is a treponemal-specific test, such as the Treponema pallidum Particle Agglutination (TP-PA) assay or an Enzyme Immunoassay (EIA). These confirmatory tests are designed to detect antibodies specific to the Treponema pallidum bacterium, and they are generally not affected by the non-syphilis causes of a BFP. If the treponemal test is non-reactive, the initial RPR result is confirmed to be a Biological False Positive.
The RPR test also provides a quantitative result expressed as a titer, which indicates the highest dilution of the blood sample that still yields a reactive result (e.g., 1:8, 1:32). Clinicians use this titer level to help interpret the result. A low titer, such as 1:1 or 1:2, can often suggest a BFP, particularly in the absence of symptoms. However, a very high titer is generally more indicative of active syphilis infection.