Syphilis Serology and Antiphospholipid Antibodies: Bidirectional Reactivity Testing across Clinical and Control...

Area of Science:

• Immunology
• Infectious Diseases
• Serology

Background:

• Antiphospholipid antibodies (aPLs) can occur during infections like syphilis, potentially causing diagnostic confusion with antiphospholipid syndrome (APS).
• Limited research exists on the bidirectional interactions between contemporary syphilis serology assays and aPL testing.
• Understanding these interactions is crucial for accurate diagnosis and patient management.

Purpose of the Study:

• To investigate potential diagnostic overlap between syphilis and antiphospholipid syndrome (APS).
• To evaluate the reactivity of syphilis serology assays with antiphospholipid antibody (aPL) assays.
• To determine if syphilis-associated aPLs represent true autoimmunity or transient cross-reactivity.

Main Methods:

• Analyzed residual sera from syphilis patients (TP-CMIA+/RPR+), aPL-positive individuals, and healthy controls.
• Utilized EUROIMMUN ELISAs for aPL testing and Abbott ARCHITECT TP-CMIA and Kehua RPR for syphilis testing.
• Performed proteome-level 3D homology search to assess epitope mimicry.

Main Results:

• No analytical cross-reactivity was found between syphilis and aPL assay reagents.
• Patients with untreated syphilis showed elevated anticardiolipin antibody (aCL) IgG and IgM, which were transient and not associated with anti-β2GPI.
• A small percentage of syphilis patients tested positive for aPLs, but these did not correlate with syphilis assay signals, and only one autoimmune aPL-positive sample was reactive in syphilis assays.

Conclusions:

• Elevated aPLs in syphilis are transient, anti-β2GPI-independent reactivity, not indicative of APS-type autoimmunity.
• Structural analysis did not support β2GPI epitope mimicry by Treponema pallidum.
• Combined RPR and TP-CMIA testing is reliable for patients with pre-existing aPL positivity.