TPPA

TPPA is the acronym for "Treponema pallidum Particle Agglutination Test" and refers to a serological laboratory procedure for the detection of antibodies against Treponema pallidum, the causative agent of syphilis. The TPPA test is a specific antibody test for syphilis and is primarily used as a confirmatory test after a positive screening result (e.g. RPR, TPHA, EIA). The TPPA test detects IgG and IgM antibodies and is therefore suitable for all stages of syphilis. It often remains positive for life after a syphilitic infection.

Advantages of the test method:

• High sensitivity and specificity.
• Simple visual result, no complex equipment required.

Limitations of the test method:

• No indication of infection stage or treatment success.
• Cross-reactions possible with rare treponematoses (e.g. Frambösie, Bejel)

Principle of the test procedure:

• Particle agglutination: Microscopically small gelatine or gelatine-coated erythrocytes/particles are coated with Treponema pallidum antigens. If patient serum containing Treponema-specific antibodies is added, these bind to the antigens on the particles. This causes the particles to clump together (agglutinate) - visible as a fine, evenly spread network at the bottom of the test well.

Technical procedure:

1. The patient's serum/plasma is pipetted onto a test plate in dilution series.
2. Addition of an antigen particle suspension.
3. Incubation at room temperature (usually 1-2 hours).
4. Reading

False positive TPPA test/ case report (Liu GL et al. 2022): A 56-year-old woman presented with headache and neck and shoulder pain. She was eventually diagnosed with antiphospholipid syndrome and monoclonal immunoglobulinemia of unknown significance (MGUS). The Treponema pallidum (TP) particle agglutination test (TPPA) and the syphilis toluidine red unheated serum test (TRUST) were positive with TPPA 1:20 480 and TRUST 1:131 072. The HIV and hepatitis tests were negative. The medical history included four miscarriages for unknown reasons. There were no clinical symptoms of syphilis. Her spouse was healthy and had a negative syphilis serology. There were no other partners. Based on the diagnosis of latent syphilis, she was given the recommended penicillin therapy. However, after three treatment cycles, the TRUST titer was 1:32 768 and the TPPA titer remained unchanged at 1:20 480. TP-IgM was positive in immunoblotting, while ELISA-IgG anti-TP assays (TP-ELISA) and fluorescent treponema antibody absorption test (FTA-ABS) as well as TP-nested PCR in blood were negative. Further examinations revealed a normal cerebrospinal fluid (CSF) with negative TPPA and TRUST as well as unremarkable results on MRI of the brain, ultrasound examination of the abdomen and Doppler echocardiography.

A false-positive non-specific syphilis serology (TRUST/Venereal Disease Research Laboratory Test) can be caused by various diseases, especially autoimmune diseases such as antiphospholipid syndrome. In addition, plasma cell diseases such as multiple myeloma and macroglobulinemia can lead to false-positive tests, but the titers are usually low and the TP-specific tests (TPPA/TP-ELISA/FTA-ABS) are negative.

1. Liu GL et al. (2022) False-positive TPPA and TRUST syphilis test results in a patient with antiphospholipid syndrome and monoclonal immunoglobulinaemia. Sex Transm Infect 98:313.
2. He TJ et al. (2016) Relationship between M-Protein of Multiple Myeloma and False Positive Syphilis Serological Results. Zhongguo Shi Yan Xue Ye Xue Za Zhi 24:478-481.