What parasitic infections cross-react with the Quest Diagnostics (Quest) Filaria Immunoglobulin G4 (IgG4) antibody test?

Cross-Reactivity of Quest Diagnostics Filaria IgG4 Antibody Test

The Quest Diagnostics Filaria IgG4 antibody test shows significant cross-reactivity with several other helminth infections, particularly Strongyloides stercoralis, and to a lesser extent with Bancroftian filariasis and other filarial nematodes. 1, 2

Parasitic Infections with Documented Cross-Reactivity

• Strongyloides stercoralis: Shows significant cross-reactivity with filarial antibody tests based on crude filarial antigens. Studies have demonstrated that both Strongyloides infection and the presence of Strongyloides antibody responses are associated with higher antifilarial antibody responses in serological assays. 2

• Bancroftian filariasis (Wuchereria bancrofti): Some sera from patients with Bancroftian filariasis have shown weak positive results in tests designed for other filarial species, indicating cross-reactivity between different filarial nematodes. 3

• Other filarial nematodes: Cross-reactivity occurs between closely related filarial species including:

  • Loa loa (African eye worm) 4
  • Onchocerca volvulus (causative agent of river blindness) 4
  • Mansonella perstans 4

Mechanisms of Cross-Reactivity

• Shared glycan antigens: Research has identified a restricted subset of cross-reactive glycans present across multiple filarial nematode species that trigger IgG responses. 4

• Common low molecular weight antigens: Studies have shown high and preferential IgG4 reactivity to a set of low molecular weight bands (15,17,20,31, and 33 kDa) across different filarial species. 5

• IgG subclass involvement: IgG1 and IgG2 appear to be the major subclasses involved in response to glycan antigens across multiple filarial infections, contributing to cross-reactivity patterns. 4

Clinical Implications

• Decreased specificity: The Infectious Diseases Society of America (IDSA) guidelines explicitly note that serology shows significant cross-reactivity among helminths, including filaria, resulting in decreased specificity of antibody tests. 6, 1

• Interpretation challenges: Test results should always be interpreted in the context of the patient's travel history, exposure risk, and clinical presentation, as false positives may occur due to cross-reactivity. 1

• Improved specificity with recombinant antigens: Tests using recombinant antigens rather than crude filarial extracts show improved specificity. For example, the B. malayi recombinant antigen (Bm14) has demonstrated better specificity with fewer cross-reactions. 2

Important Diagnostic Considerations

• Diagnostic algorithm: When filariasis is suspected, a combination of serological testing, microscopic examination of blood, and molecular testing may be necessary for accurate diagnosis. 6

• Timing of testing: The majority of patients demonstrate increased IgM or IgG titers by the second week of illness, but patients might lack diagnostic antibody titers in the first 7 days of illness. 6

• Persistence of antibodies: Antibodies may persist for months to years after successful treatment, making it difficult to distinguish between current and past infections. 6

• Alternative diagnostic approaches: Nucleic acid amplification tests (NAATs) may offer higher specificity for differentiating between filarial species when cross-reactivity is a concern. 6

Pitfalls to Avoid

• Relying solely on serological results: Due to cross-reactivity, clinical decisions should not be based on a reactive IgG4 serologic result alone. 6

• Ignoring epidemiological context: Interpretation of test results should always consider the geographic distribution of different filarial species and the patient's travel history. 6

• Overlooking other diagnostic methods: Microscopy remains the cornerstone of laboratory identification for many parasitic infections and should be used in conjunction with serological testing when appropriate. 6