Increased Complement C1q Level Marks Active Disease in Human Tuberculosis

Abstract

BackgroundComplement functions as an important host defense system and complement C5 and C7 have been implicated in immunopathology of tuberculosis. However, little is known about the role of other complement components in tuberculosis.MethodsComplement gene expression in peripheral blood mononuclear cells of tuberculosis patients and controls were determined using whole genome transcriptional microarray assays. The mRNA and protein levels of three C1q components, C1qA, C1qB, and C1qC, were further validated by qRT-PCR and enzyme-linked immunosorbent assay, respectively. The percentages of C1q expression in CD14 positive cells were determined by flow cytometry. Finally, C1qC protein level was quantified in the pleural fluid of tuberculosis and non-tuberculosis pleurisy.ResultsC1q expression increases significantly in the peripheral blood of patients with active tuberculosis compared to healthy controls and individuals with latent TB infection. The percentage of C1q-expressing CD14 positive cells is significantly increased in active TB patients. C1q expression in the peripheral blood correlates with sputum smear positivity in tuberculosis patients and is reduced after anti-tuberculosis chemotherapy. Notably, receiver operating characteristic analysis showed that C1qC mRNA levels in peripheral blood efficiently discriminate active from latent tuberculosis infection and healthy controls. Additionally, C1qC protein level in pleural effusion shows improved power in discriminating tuberculosis from non-tuberculosis pleurisy when compared to other inflammatory markers, such as IL-6 and TNF-α.ConclusionsC1q expression correlates with active disease in human tuberculosis. C1q could be a potential diagnostic marker to discriminate active tuberculosis from latent tuberculosis infection as well as tuberculosis pleurisy from non-tuberculosis pleurisy.

Host sirtuin 1 regulates mycobacterial immunopathogenesis and represents a therapeutic target against tuberculosis

“…1I) (21). In TB patients undergoing chemotherapy (18, 20), SIRT1 mRNA levels increased after 2 to 3 months of therapy and reached levels comparable with those observed in healthy/latent TB individuals by the sixth month of treatment (Fig. 1J and fig.…”

Complement activation in Glioblastoma Multiforme pathophysiology: Evidence from serum levels and presence of complement activation products in tumor tissue

“…We observed an increase in C1q serum concentration in comparison to our healthy controls, which can be attributed to reactive upregulation by the tumor process as observed in infectious diseases as active tuberculosis and bacterial meningitis (Cai et al, 2014;Mook-Kanamori et al, 2014).…”

Antibodies and tuberculosis

“…Complement and IgG binding of live M.tb h37Rv increases the number of viable intracellular bacilli, rather than reduce bacterial load which would be expected if antibody-dependant complement-mediated destruction occurred in TB [86]. This is in keeping with the previously mentioned activation of C1q that could be enhancing uptake of bacilli into their intracellular niche [20].…”

“…Fcγr1A binds antibody principally of the IgG1 and IgG3 subtype and is expressed mainly in macrophages and dendritic cells [19]. The expression of complement C1q, which forms immune complexes with immunoglobulin, is also elevated during active TB and is associated with increased disease severity [17], [20]. Further analysis of transcription studies have shown TRIM21, a recently identified intracellular antibody receptor, to also be elevated in disease [21].…”