Detection of Antigen 38-kDa in Cerebrospinal Fluid using Recombinant Antibody as a Novel Diagnostic Test for Tuberculous Meningitis

The diagnosis of tuberculous meningitis (TBM) continues to pose significant difficulties owing to the inherent constraints of presently available diagnostic techniques. This study aimed to evaluate the diagnostic potential of Antigen 38-kDa (Ag38) detection in cerebrospinal fluid (CSF) using recombinant antibodies. This cross-sectional study enrolled 36 participants at Saiful Anwar General Hospital, Indonesia: 12 culture-confirmed TBM patients, 12 clinically-diagnosed TBM patients, and 12 non-TBM controls. CSF samples were analyzed using ELISA with recombinant Ag38 antibodies as primary antibodies and both IgM and IgG as secondary antibodies. Diagnostic performance was assessed through sensitivity, specificity, and ROC curve analysis. As a result, using IgG as secondary antibody, CSF Ag38 levels were significantly higher in culture-confirmed TBM (0.589 ± 0.147) and clinically-diagnosed TBM (0.579 ± 0.158) compared to controls (0.402 ± 0.036) (P = 0.004). Using an optimal cutoff threshold of 0.444, IgG-based detection demonstrated 83.3% sensitivity and 91.7% specificity, achieving a positive predictive value of 90.1% and a negative predictive value of 84.6%. ROC analysis demonstrated excellent diagnostic performance with AUC of 0.854 (P = 0.004). Detection of Ag38 in CSF using recombinant antibodies, particularly with IgG as secondary antibody, shows promising diagnostic potential for TBM. This method could serve as a valuable addition to the current diagnostic arsenal for TBM.