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

BACKGROUND

Antiphospholipid antibodies (aPLs) may arise during infection, including syphilis, creating diagnostic overlap with antiphospholipid syndrome (APS). Research evaluating bidirectional interactions between modern syphilis serology and aPL assays remains limited.

METHODS

Residual sera were grouped as Treponema pallidum chemiluminescent microparticle immunoassay positive (TP-CMIA+)/rapid plasma reagin positive (RPR+) syphilis (n = 200), aPL-positive specimens tested by syphilis serology (n = 218), and healthy controls (n = 200). aPL testing used EUROIMMUN ELISAs; syphilis testing used Abbott ARCHITECT TP-CMIA and Kehua RPR. Manufacturer kit controls were cross-tested. A proteome-level 3D homology search was conducted following published protocols.

RESULTS

The RPR kit positive control showed no reactivity in any aPL assay. TP-CMIA+/RPR+ samples had higher anticardiolipin antibody (aCL) IgG than healthy controls (median 2.49 vs 2.00 RU/mL; P = 1.33 × 10-10), no difference in aCL IgM, and slightly lower anti-β2GPI IgM (P = 0.0183) and IgG (P = 4.0 × 10-6). Of these, 23/200 (11.5%) were aPL-positive, exhibiting elevated RPR titers (P = 3.3 × 10-6) and TP-CMIA signal-to-cutoff (S/CO) (median 16.26 vs 14.94; P = 0.004), without correlation between S/CO and aPL levels. Among 218 autoimmune aPL-positive samples, 1 (0.46%) was TP-CMIA+/RPR+. In cytokine-assessed samples (n = 44), Interferon-γ-inducible Protein 10 was higher in aCL-positive cases (median 2661 vs 865 pg/mL; P = 0.0149). aCL IgM and IgG were markedly elevated in pretreatment syphilis vs posttreatment (all P < 0.0001), while anti-β2GPI remained unchanged. 3D homology screening found one β2GPI-domain V-like structure in the T. pallidum proteome but lacked APS-epitope features.

CONCLUSIONS

No analytical cross-reactivity between assay reagents was detected. Apparent aCL elevations in untreated syphilis reflect anti-β2GPI-independent, transient reactivity rather than APS-type autoimmunity, and structural analysis provides no strong support for β2GPI epitope mimicry. Combined RPR and TP-CMIA testing remains reliable in patients with preexisting aPL positivity.