Cellular Tests for Lyme Disease Not Fit for Clinical Use

Cellular tests for Lyme disease had low specificity compared with serologic tests and were deemed inappropriate for use in clinical practice, according to results of a study published in The Lancet Infectious Diseases.

Researchers assessed the sensitivity and specificity of 3 cellular tests for Lyme disease, including Spirofind Revised, iSpot Lyme, and the lymphocyte transformation test memory lymphocyte immunostimulation assay (LTT-MELISA). These tests were compared with standard 2-tier serologic tests (STTT) in a nationwide, prospective, multiple-gate case-control study in the Netherlands.

Overall, 271 patients with and 228 without (controls) were included in the analysis, of whom the mean age was 53 and 54 years, and 57% and 54% were women, respectively. Of patients with Lyme disease, 245 had early-localized disease and 28 had disseminated disease. Of patients in the control group, 41 had potentially cross-reactive conditions. Clinical data were captured from patients at baseline and at 12 weeks after study enrollment. Blood samples were obtained from patients with Lyme disease at baseline, and then at 6 and 12 weeks; patients in the control group underwent clinical and laboratory assessments only at baseline.

For patients in the control group, STTTs were performed among 216, with results showing STTTs had a specificity of 94.7% (95% CI, 91.5-97.7; 216 of 228). Compared with STTTs, specificity was decreased for all 3 cellular tests, with specificity results of 81.9% (95% CI, 76.1-87.2), 31.1% (95% CI, 21.5-40.3), and 52.6% (95% CI, 44.9-60.3) for the Spirofind, iSpot Lyme, and LTT-MELISA, respectively.

Results obtained from patients in the Lyme disease group showed that the sensitivity of the Spirofind (43.1%; 95% CI, 36.4-50.4) and iSpot Lyme (54.3%; 95% CI, 44.5-63.7) tests were increased compared with STTT (28.1%; 95% CI, 23.0-33.6). The only cellular test that failed to outperform STTT in regard to sensitivity was the LTT-MELISA (30.3%; 95% CI, 36.4-50.4).

Further analysis of patients with Lyme disease was performed to assess for meaningful changes among the 3 cellular tests in regard to reactivity results. Of the 3 cellular tests, only the LTT-MELISA showed an increase in reactivity between results obtained at baseline (30.3%) and those obtained at 6 weeks (46.4%).

This study was limited by the lack of a universal reference, the different recall periods for tick bites between patients with vs without Lyme disease, and insufficient power due to missing data.

According to the researchers, “[these] findings suggest that patients with suspected Lyme [disease] are no closer than before this study to an assay that can reliably diagnose Lyme [disease] across all disease stages and… differentiate between an active and cured infection.” They concluded that these “… findings underscore the need to improve Lyme [disease] diagnostics and might serve as a stepping-stone to research to that end.”

Disclosure: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures. 

Reference

Baarsma ME, van de Schoor FR, Gauw SA, et al. Diagnostic parameters of cellular tests for Lyme borreliosis in Europe (VICTORY study): a case-control study. Lancet Infect Dis. Published June 14, 2022. doi:10.1016/S1473-3099(22)00205-5