Evaluation of heat shock proteins for discriminating between latent tuberculosis infection and active tuberculosis: A preliminary report

Abstract

The diagnosis of a latent tuberculosis infection (LTBI) is of the utmost concern. The available tests, the tuberculin skin test (TST) and the Quantiferon-TB Gold test (QFT-G) cannot discriminate between active TB and LTBI. Therefore, the aim of the study is to identify new biomarkers that can discriminate between active TB and LTBI and can also assess the risk of the individual developing active TB. In total, 55 blood samples were collected, of which 10 samples were from the active TB infection group, 10 were from the high-risk exposure group, 23 were from the low-risk exposure group, and 12 were from healthy controls living in a non-TB endemic area. A panel of heat shock proteins (Hsps), including host Hsp25, Hsp60, Hsp70, and Hsp90 and Mycobacterium tuberculosis (MTB) Hsp16, were evaluated in all of the collected samples using ELISA. The levels of the host Hsp(s) (Hsp25, Hsp60, Hsp70 and Hsp90) and MTB Hsp16 were significantly (p<0.05) elevated in the active TB group compared to the high-risk exposure group, the low-risk exposure group and the control group. Notably, the levels of the same panel of Hsp(s) were elevated in the high-risk exposure group compared to the low-risk exposure group. On follow-up, out of the 10 high-risk exposure participants, 3 converted into active TB, indicating that this group has the highest risk of developing TB. Thus, the evaluated panel of Hsp(s) can discriminate between LTBI and active TB. They can also identify individuals who are at the highest risk of developing active TB. Because they can be rapidly detected, Hsp(s) have an edge over the existing diagnostic tools for LTBI. The evaluation of these proteins will be useful in designing better diagnostic methods for LTBI.

Changes in the Membrane-Associated Proteins of Exosomes Released from Human Macrophages after Mycobacterium tuberculosis Infection

“…Previous studies have shown that some of these proteins play important roles during Mtb infection. Shekhawat et al ., showed that human HSP proteins (including HSP90) were increased in sera from individuals with a high risk of being latently infected with Mtb, suggesting HSP proteins as potential biomarkers for LTBI24. We observed that HSP90 was significantly higher in exosomes from infected cells.…”

Evaluation of Rv0220, Rv2958c, Rv2994 and Rv3347c of Mycobacterium tuberculosis for serodiagnosis of tuberculosis

“…The identification of valuable M. tuberculosis antigens is vital to the improvement of serodiagnostic methods of TB. In recent years, comparative genomic studies have identified some promising recombinant proteins for TB serodiagnosis such as ESAT‐6, CFP‐10, Hsp60 (Shekhawat et al ., ), PE35 (Baumann et al ., ), PPE57 (Chen et al ., ), PPE68 (Pourakbari et al ., ), Rv1168c, Rv1985c and Rv3878 (Dosanjh et al ., ). The combination of antigens ESAT‐6 and CFP‐10 has been used to identify individuals with active TB in commercial tests.…”

Composition and Clinical Significance of Exosomes in Tuberculosis: A Systematic Literature Review

“…Another study that employed enzyme-linked immunosorbent assay (ELISA) reported host HSP25, HSP60, HSP70, and HSP90 proteins in the serum samples of TB patients [73]. A different study reported host proteins such as LAMP-1 [62,74] and teraspanins like CD9, CD63, CD81, and CD86 [75].…”