Predictive value of soluble haemoglobin scavenger receptor CD163 serum levels for survival in verified tuberculosis patients

Abstract

Pre-treatment serum levels of sCD163 were measured in a cohort of 236 suspected tuberculosis (TB) cases from Guinea-Bissau, with a median follow-up period of 3.3 years (range 0-6.4 years). In 113 cases, the diagnosis of TB was verified by positive sputum microscopy and/or culture. Among the verified TB cases, a decreased survival rate was found in 27 patients with sCD163 levels above the upper reference limit (3.95 microg/mL). The difference in survival was significant during TB treatment (log rank, p<0.02) and after long-term follow-up (log rank, p<0.001). The decrease in survival rate during TB treatment remained significant in a multivariate Cox model controlling for human immunodeficiency virus (HIV) status, age and gender, with a mortality increase of 1.19 (95% CI, 1.04-1.36) per microg of sCD163, and a hazard ratio (HR) for sCD163 levels above the upper reference limit of 4.18 (95% CI, 1.06-16.4). The difference was not significant after excluding patients with concomitant HIV-1 and HIV-2 infection in Kaplan-Meier analyses (log rank, p 0.11). In contrast, the difference in survival remained significant in Kaplan-Meier analyses after long-term follow-up, even after excluding patients with concomitant HIV-1 and HIV-2 infection (log rank, p 0.002). In the Cox model, the mortality increase per microg of sCD163 was 1.27 (95% CI, 1.14-1.40), with an HR for elevated sCD163 levels of 2.85 (95% CI, 1.44-5.63). The HRs for concomitant HIV-1 and HIV-2 infection were 6.92 (95% CI, 3.28-14.58) and 2.48 (95% CI, 1.09-5.67), respectively. Thus, sCD163 levels appeared to be an independent predictor of survival in verified TB patients.

Identification of biomarkers for tuberculosis disease using a novel dual-color RT–MLPA assay

“…[9][10][11][12][13][14]17,18 Several biomarkers identified earlier to discriminate between TB cases and LTBIs in German and South African cohorts (for example, FCGR1A (CD64), LTF and RAB33A), 13,19 were confirmed in the current study cohort from the Gambia. Intriguingly, FCGR1A is the only biomarker from our signature that was also identified by a recent large-scale microarray analysis in UK and South-African TB patients, 16 discriminating active TB disease from LTBI, despite being not specific for TB when compared with other inflammatory diseases.…”

“…The complete probe set contained genes that have been associated with active TB disease or protection against disease in literature (IL4/IL4d2, CCL22, CD163, TGFBR2), [9][10][11][12] genes identified by microarray that were differentially expressed between PBMCs from active TB patients and healthy household contacts (FPR1, BPI, MARCO, SEC14L1, RAB24, RAB13, RAB33A, FCGR1A, LTF), 13 genes identified by microarray that were differentially expressed between tissue located near and distant from tuberculomas (CCR7, CCL13, IL22RA1, Figure 3 Reproducibility of the dcRT-MLPA assay. Two independent dcRT-MLPA assays were performed on whole-blood RNA extracted from five PAXgene tubes collected from 12 Dutch healthy donors at two different time points.…”

Tuberculosis is associated with expansion of a motile, permissive and immunomodulatory CD16+ monocyte population via the IL-10/STAT3 axis

“…In a second step, these results need to be confirmed in a larger cohort of individuals from different genetic background. Indeed, there is only one study that correlated the plasma concentration of sCD163 to the survival of verified TB patients [40]. However, there has been no confirmation of these results ever since, and more importantly, there is no actual evaluation available on the effect of anti-TB drugs on sCD163 levels until now.…”

“…However, there has been no confirmation of these results ever since, and more importantly, there is no actual evaluation available on the effect of anti-TB drugs on sCD163 levels until now. Interestingly, sCD163 is considered as a valuable marker of the activation of an M2-like monocyte-macrophage program and biomarkers of disease activity in SLE [25,40], alluding to a critical biological significance for the presence of this soluble receptor as immune response biomarkers in TB disease.…”

“…Given that membrane-bound CD163 and MerTK receptors are subjected to inflammation-driven shedding [38,39], we hypothesized that chronic infection with Mtb may also lead to the shedding of these receptors from the surface of circulating monocytes, and thus increase the expression of soluble CD163 (sCD163) and MerTK (MerTK ectodomain: sMer) in the serum of TB patients. Aside from a single report describing the circulating sCD163 as a predictive value for patient survival [40], there is virtually no information about this scavenger receptor and MerTK in the TB context. We thus evaluated the sera from pulmonary TB patients and revealed a progressively increasing trend in the levels of sCD163, particularly striking in cases with an advanced degree of the disease ( Figure 3D).…”