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Updated: Jun 30, 2026
Simultaneous Detection of Different Antibody Classes in a Multiplexed Serological Test
Published on: July 14, 2023
Syphilis Serology and Antiphospholipid Antibodies: Bidirectional Reactivity Testing across Clinical and Control
Xiaomin Shi1, Fengtian Feng1, Kaisong Hu1
1Department of Laboratory Medicine, Peking University First Hospital, Beijing, China.
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.
