Adjunct Diagnostic Accuracy of Antigen-specific Interleukin-2 for Latent Tuberculosis Infection in Pregnancy.

BACKGROUND: Pregnancy modulates immune responses against() infection. Cytokines, including interleukin-2 (IL-2), play a crucial role incontainment, mainly by inducing the proliferation of T cells. However, the role of IL-2 in latent tuberculosis (TB) infection (LTBI) screening has not been completely explored. We, therefore, evaluated the diagnostic accuracy and optimal cutoff value (OCV) of IL-2 as a potential adjunct biomarker for screening LTBI during pregnancy.

METHODS: We enrolled pregnant women without previous active TB at Kawempe National Referral Hospital, Uganda, in 2020. We tested for LTBI using the QuantiFERON-TB Gold-Plus assay. Blood in quantiFERON blood collection tubes was stimulated withpeptides of ESAT-6 and CFP-10 and following incubation, IL-2 culture supernatant levels were measured in an 11-plex Luminex assay using the Luminex® 100/200™ System with xPONENT® 3.1 software. LTBI positivity was defined as an IFN-γ concentration ≥0.35 IU/mL (calculated as TB1/TB2-Nil). A receiver operator characteristic curve was plotted to assess the diagnostic performance of-specific IL-2 culture supernatants using STATA 18.0. The OCV was determined using the Youden index, considering sensitivity and specificity.

RESULTS: Of 159 participants, the median gestational age was 26.1 (IQR: 20.0-31.6) weeks, 8.2% (n = 13) had HIV, and 10.1% (n = 16) were recent TB contacts. Overall, 79 (49.7%) had LTBI.-specific IL-2 levels were significantly higher in LTBI than in the non-LTBI group (847.9 (418.2-1309.1) versus 147.73 (100.38-207.19) pg/mL,< .001). IL-2 achieved an AUC of 0.88 (95% CI: 0.82-0.93), with 76% sensitivity and 96% specificity. IFN-&#x3b3; showed an AUC of 0.83 (95% CI: 0.76-0.90), with 78% sensitivity and 90% specificity. The combined IL-2 + IFN-&#x3b3; response yielded the highest accuracy, with an AUC of 0.89 (95% CI: 0.83-0.94), 77% sensitivity, and 95% specificity.

CONCLUSIONS: -specific IL-2 culture supernatant levels showed good discriminatory power for LTBI detection in pregnancy, comparable to IFN-&#x3b3;, with the combined IL-2+ IFN-&#x3b3; response yielding the highest accuracy. These findings support the potential utility of IL-2, alone or with IFN-&#x3b3;, as an adjunct biomarker for LTBI screening in pregnant women, warranting further validation in larger, diverse cohorts.