Anti-Treponema Immunohistochemistry Cross-Reactivity Reported with Non-Treponema Spirochetes

Syphilis has different histopathologic presentations, and it can mimic a significant number of entities while human intestinal spirochetosis is characterized by the presence of a layer of spirochetes adherent to the apical epithelial surface of the colorectal mucosa.

The spirochete species most often associated with this finding in humans are Brachyspira pilosicoli and Brachyspira aalborgi. B.pilosicoli has been identified in other animals, such as pigs, rodents, and chickens, suggesting that the acquisition can be zoonotic. Higher prevalence rates are reported in developing countries, homosexual men, and human immunodeficient virus (HIV)-positive patients, who are also at increased risk for syphilis.


Medical scientists at the Cleveland Clinic (Cleveland, OH, USA) investigated the histopathologic findings of intestinal spirochetosis, which are different from those of syphilis. They used biopsies from eight patients with intestinal spirochetosis to evaluate the potential of cross-reactivity of a commercially available polyclonal antibody directed against Treponema pallidum, the causative agent of syphilis.

Hematoxylin-eosin stains and Warthin-Starry stains were available in all cases. The slides were reviewed and the diagnoses confirmed. In all biopsies, the hematoxylin-eosin–stained sections revealed a thickened and shaggy basophilic band on the apical cell membrane of the colorectal epithelium; Warthin-Starry stain demonstrated numerous spirochetes. Immunohistochemistry for T. pallidum (Biocare Medical, Concord, CA, USA) was performed on 2-μm sections of paraffin-embedded tissues, and the tissues were incubated 16 minutes at 37 °C. The protein-antibody complexes were located with the iView DAB Detection kit (Ventana Medical Systems, Oro Valley, AZ, USA). All biopsies showed strong positivity for the polyclonal antibody for T. pallidum.

The authors concluded that the potential for cross-reactivity of commercially available antibodies for T. pallidum with other spirochete species poses a potential diagnostic pitfall when biopsies are taken from locations wherein spirochetes may be encountered. The anti–T pallidum immunohistochemical stain remains a significant advance in the detection of T. pallidum spirochetes in the biopsies of patients with syphilis. It is important for the pathologist to be aware of this cross-reactivity with non-Treponema spirochetes. The histopathologic diagnosis of syphilis should not rest entirely on a positively staining spirochete. Rather, the diagnosis should be made based on the presence of the spirochetes with the appropriate histopathologic findings. The study was published in the October 2016 issue of the journal Archives of Pathology & Laboratory Medicine.

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