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

Abstract Background Pregnancy modulates immune responses against Mycobacterium tuberculosis (Mtb) infection. Cytokines, including interleukin-2 (IL-2), play a crucial role in Mtb containment, 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 with Mtb peptides 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 Mtb-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. Mtb-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, P < .001). IL-2 achieved an AUC of 0.88 (95% CI: 0.82–0.93), with 76% sensitivity and 96% specificity. IFN-γ showed an AUC of 0.83 (95% CI: 0.76–0.90), with 78% sensitivity and 90% specificity. The combined IL-2 + IFN-γ response yielded the highest accuracy, with an AUC of 0.89 (95% CI: 0.83–0.94), 77% sensitivity, and 95% specificity. Conclusions Mtb-specific IL-2 culture supernatant levels showed good discriminatory power for LTBI detection in pregnancy, comparable to IFN-γ, with the combined IL-2+ IFN-γ response yielding the highest accuracy. These findings support the potential utility of IL-2, alone or with IFN-γ, as an adjunct biomarker for LTBI screening in pregnant women, warranting further validation in larger, diverse cohorts.