Circulating immune complexes (CIC's) are associated with disease progression in Tuberculosis (TB) though their role in pathogenesis is still unclear. Hence the present study was undertaken to identify proteins of diagnostic potential in tuberculosis by proteomic profiling of CIC's. Serum samples from tuberculosis patients (n=28), latent TB (n=10) and healthy (n=15) individuals were collected and CIC's levels were estimated by ELISA. CIC's were isolated by 7% Polyethylene Glycol precipitation and were subjected to proteomic analysis. Bioinformatic analysis and functional annotation of identified proteins was performed using Mascot search engine and PANTHER respectively. Identified protein was validated by ELISA. Statistical analysis was performed with SPSS version 16 and Graph pad prism 5. The mean CIC concentration in TB, latent TB and healthy individuals was found to be 38.23±11.45, 24.43±15.09, and 8.61±2.47µg/ml respectively. A total of 74, 48 and 60 proteins were identified in CIC's from of TB, latent TB and healthy individuals respectively. Among identified proteins the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of C1qC to distinguishing TB patients from controls (with respect to both latent TB and healthy controls) was found to be 87.18% , 93.33%, 94.44%, 84.85% and 89.86% respectively. Our exploratory analysis suggests that immune-complex based assays might provide better alternate to invasive diagnostic techniques especially in diagnosis of extra pulmonary TB. However, further elaborate studies are required.

A B S T R A C T BACKGROUNDDespite several efforts, tuberculosis (TB) continues to be a global concern. For proper management of TB, more sensitive and specific biomarkers for early and accurate diagnosis of TB are still required. Blood based host markers are more appealing as an alternate to sputum-based diagnostics. Thus, in the present study, we evaluated the potential of Serum Complement Component 1 Q Subcomponent C (C1qC) as a marker for tuberculosis. METHODSSerum samples from 84 subjects which included 39 smear positive pulmonary TB patients and 45 controls (Latent TB n=15, Healthy n= 15 and patients with respiratory diseases other than TB n= 15) were collected and Enzyme Linked Immunosorbent Assay was performed to estimate the serum C1qC levels. RESULTSThe mean (±SD) serum C1qC levels in TB, Healthy, Latent TB and patients with respiratory diseases other than TB was found to be 21.80 (±4.39), 13.64 (±1.32), 15.18(±1.29) and 17.31(±1.87) pg/ml respectively. The AUC of serum C1qC to discriminate TB patients from controls was found to be 0.924 (95% CI, 0.869-0.978). At an optimal cut-off value of 16.99 pg/ml, the sensitivity and specificity of serum C1qC to discriminate TB from controls was found to be 84.62% (95% CI, 69.47%-94.14%) and 84.44% (95% CI, 70.54%-93.51%) respectively with a likelihood ratio of 5.44. CONCLUSIONSThe levels of serum C1qC in TB patients was found to be significantly higher than controls. C1qC seems to be a promising marker for the diagnosis and therapeutic monitoring of TB, though further elaborate studies in larger cohorts are required to establish the role for C1qC in the diagnosis and therapeutic monitoring of TB.