Why can RPR and VDRL tests produce false-positive results?

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Scanning electron micrograph of Treponema pallidum, the spirochete bacterium that is the causative agent of syphilis. — syphilis Scanning electron micrograph of *Treponema pallidum*, the spirochete bacterium that is the causative agent of syphilis.

The RPR (rapid plasma reagin) and VDRL (Venereal Disease Research Laboratory) tests are nontreponemal serological tests used to detect syphilis. These tests function by identifying reagin, an antibody produced by the body in response to the infection.1

The potential for false-positive results in these tests arises because they rely on the reaction of reagin with a lipid antigen typically derived from beef heart. Because this antigen is not specific to the spirochete Treponema pallidum, the tests can occasionally react to other conditions or substances that trigger similar antibody responses.1

Due to this lack of specificity, nontreponemal tests are generally used for screening, and any positive result requires confirmation with a more specific treponemal test, such as the TPHA or FTA-ABS, which directly detect antibodies that specifically target T. pallidum.1