Our study analyzed differentially expressed genes in ATB, LTBI, and HC in different GEO datasets and screened for genes FCGR1A and AIM2 that were differentially expressed in both ATB, LTBI, and HC. The expression levels of FCGR1A and AIM2 were found to be increasing in ATB, LTBI, and HC. The result was also validated using real-time PCR and ELISA, and we showed that the genes FCGR1A and AIM2 were found to be up-regulated in patients with ATB compared to HC, and the concentration of FCGR1A protein was higher in the serum of patients with ATB relative to HC, with a ROC analysis showing the area under the curve of FCGR1A protein was > 0.8.
FCGR1A, known as Fc gamma receptor Ia, encodes a protein that plays an important role in the immune response and is a high-affinity Fc-gamma receptor. A study by Desta Kassa et al. found that FCGR1A has the potential to differentiate between active and inactive tuberculosis in HIV + patients in Ethiopia [12]. Another study showed that FCGR1A could be used as a biomarker for TB treatment detection and treatment outcome prediction [13]. Validation by Harriet D Gliddon et al. confirmed that FCGR1A, ZNF296, and C1QB could be used as biomarkers to differentiate LTBI from ATB [14]. Meng Shao et al. analyzed the transcriptional profiles between LTBI and ATB in children by bioinformatics analysis and found that FCGR1A could be used to discriminate between latent and active TB in children [15]. Combined with the analysis of our study, FCGR1A can be used as a diagnostic and therapeutic monitoring biomarker for different infection statuses of M. tuberculosis, independent of age, and HIV infection.
AIM2 (Absent in melanoma 2), is abundantly expressed in tissues such as lymph nodes, cecum, and spleen. Hiroyuki Saiga et al. showed that AIM2 deficient mice are highly susceptible to intratracheal infection by M. tuberculosis, which is associated with defective IL-1β and IL-18 production and impaired Th1 responses AIM2 plays an important role in M. tuberculosis infection by recognizing M. tuberculosis DNA [16]. A study by Jialu Ma et al. found that AIM2 facilitates host survival and limits the replication of M. tuberculosis in vivo [17]. Previous studies have shown that AIM2 contributes to the host clearance of Mycobacterium tuberculosis. Our study found that AIM2 expression levels were up-regulated in TB patients, contributing to the diagnosis of TB.
Our experiment validated that genes FCGR1A and AIM2 were differentially expressed in ATB and HC, suggesting that genes FCGR1A and AIM2 are expected to be potential biomarkers for the diagnosis of ATB. Combined with the results of the previous analysis, the expression levels of genes FCGR1A and AIM2 showed an increasing trend in ATB, LTBI, and HC, suggesting that FCGR1A and AIM2 could be used as biomarkers to predict different statuses of disease after infection with M. tuberculosis. Dynamic monitoring of changes in the expression levels of genes FCGR1 and AIM2 might provide insight into the different infection statuses of M. tuberculosis and provide biomarkers for monitoring the efficacy of treatment of M. tuberculosis infection. This study provides a basis for identifying the different infection statuses of M. tuberculosis and reveals the biological characteristics of M. tuberculosis infection.
There are limitations to this study, such as a small number of samples and a lack of LTBI data for experimental validation, so more studies involving larger populations are needed to confirm our findings.