Pre-treatment IFN-γ levels are associated with chronic progression in patients with brucellosis: a retrospective study

Background: Chronic brucellosis may lead to persistent symptoms and multisystem complications, but objective markers for identifying patients at high risk of chronic progression remain lacking. This study investigated the association between pre-treatment interferon-gamma (IFN-γ) levels and chronic progression in brucellosis. Methods: This single-center retrospective study included patients diagnosed with brucellosis at the General Hospital of Ningxia Medical University between January 2021 and June 2025. The primary outcome was progression to chronic brucellosis. Logistic regression was used to assess the association between pre-treatment IFN-γ levels and chronic progression risk. Restricted cubic spline (RCS) and subgroup analyses were performed to examine the dose-response relationship and the robustness of the findings. Candidate predictors were selected using complementary statistical and feature-selection approaches, and an exploratory baseline model was constructed to assess whether IFN-γ provided incremental predictive information. Results: Multivariable logistic regression showed that pre-treatment IFN-γ levels were independently and inversely associated with chronic progression risk. In the fully adjusted model, this association remained consistent when IFN-γ was analyzed as a continuous variable, a tertile-based categorical variable, or a binary variable using the cutoff derived from RCS analysis, supporting the robustness of the findings. RCS analysis demonstrated a significant nonlinear inverse association between IFN-γ levels and chronic progression risk, with an inflection point around 13.47. Subgroup analyses showed that this association was generally consistent across age, sex, exposure history, occupation, and comorbidity strata. Adding IFN-γ to the baseline model produced a modest but statistically significant increase in discrimination, with the AUC increasing from 0.855 (95% CI: 0.795-0.915) and 0.894 (95% CI: 0.847-0.942; ΔAUC = 0.039; P = 0.021). Improvements in net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were also observed. Conclusions: Higher pre-treatment IFN-γ levels were independently associated with a lower risk of chronic progression in patients with acute brucellosis. IFN-γ may serve as a promising exploratory biomarker for early risk stratification of chronic progression in brucellosis. However, the prediction model was not validated, and its clinical utility requires confirmation in multicenter prospective cohorts.