Evaluation of cytokines in peripheral blood mononuclear cell supernatants for the diagnosis of tuberculosis

Figures & data

Table 1 Demographic characteristics of the study participants

Characteristics	Controls n=21 (%)	TB cases n=73 (%)
Age, mean in years ± SD	41±13.5	39.8±12.7
Gender
Male	4 (19)	59 (81)
Female	17 (81)	14 (19)
HIV status
Positive	3 (14)	20 (27)
Negative	13 (62)	53 (73)
Unknown	5 (24)
BMI
Normal, BMI ≥ 18.5	16 (76)	44 (60)
Malnourished, < 18.5	0	29 (40)
Unknown	5 (24)
Method of TB diagnosis	n/a
GeneXpert		32 (44)
Culture and DST		34 (46)
Clinically diagnosed		7 (10)
Final Treatment outcome	n/a
Cure		21 (29)
Treatment complete		23 (32)
Failed		1 (1)
Died		11 (15)
Defaulted		3 (4)
Transfer out/unknown		14 (19)

Abbreviations: BMI, body mass index; DST, drug susceptible testing; NA, not applicable.

Table 2 Association of ALS and other cytokines in predicting TB cases and hospitalized controls

Biomarkers	Number of participants	Case status	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)
ALS, VEGF, TNF-α, and IL-2	66	Confirmed TB cases	82.8	81.0	93.0	60.7
ALS, VEGF, TNF-α, and IL-2	73	All TB cases	82.2	76.2	92.3	55.2

Note: All TB cases – this includes microbiologically confirmed cases (n=66) and clinically diagnosed cases (n=7).

Abbreviations: NPV, negative predictive values; PPV, positive predictive values; ALS, antibody in lymphocyte supernatant; TNF-α, tumor necrosis factor-alpha; VEGF, vascular endothelial growth factor; TB, tuberculosis.

Figure 1 Unstimulated PBMC cytokine responses among TB cases and controls.

Notes: (A–F): TB cases are shown in green and hospitalized controls in red. Data presented in log₁₀ pg/ml. The figures are arranged depending on their scale, from the highest scale (A), consecutively to the lowest scale (F). Lines show the median with interquartile ranges. Mann–Whitney U test was used for comparison between groups. Bonferroni correction was applied, and a P-value of 0.002 was considered significant.

Abbreviations: FGF-basic, fibroblast growth factor-basic; G-CSF, granulocyte-colony stimulating factor; GM-CSF, granulocyte macrophage-colony stimulating factor; IFN-γ, interferon-gamma; McP-1, monocyte chemoattractant protein-1; MIP-1α, monocyte inducible protein-1α; MIP-1β, monocyte inducible protein-1β; PBMC, peripheral blood mononuclear cell; PDGF-bb, platelet-derived growth factor-bb; TB, tuberculosis; TNF-α, tumor necrosis factor-alpha; VEGF, vascular endothelial growth factor.

Figure 2 comparison of cytokine levels among TB cases before and after 4 weeks of TB treatment.

Notes: Figures depicting the longitudinal changes of cytokine, chemokine, and growth factor expression among TB cases, n=73. Concentrations are shown at baseline and at week 4 of treatment and results are expressed as Log₁₀ pg/ml. Statistical analyses were performed using non-parametric Wilcoxon paired test and a P=0.002 was considered significant. FGF-basic significantly increased over time (P=0.002).

Abbreviations: TNF-α, tumor necrosis factor-alpha; FGF-basic, fibroblast growth factor-basic; MCP-1, monocyte chemoattractant protein-1; TB, tuberculosis; TNF-α, tumor necrosis factor-alpha; VEGF, vascular endothelial growth factor.