TABLE 1

Candidate correlates of tuberculosis (TB) risk

	Biomarker	Neonates, children, adolescent or adult population	Location	[Ref.]
Validated correlates of TB risk
Commercial or traditional tests for LTBI diagnosis	RD1-specific immune response in IGRA, immune sensitisation to PPD in TST	Children and adults	Global	[22, 44, 45]
Molecular tests	mRNA expression signature of 16 IFN response genes	Adolescents	Africa	[52]
Cell activation markers	Increased HLA-DR-expressing CD4⁺ T-cells	Infants	Africa	[63]
Blood cell counts	Elevated monocyte/lymphocyte ratio	Adults	Africa	[111, 114]
Unvalidated correlates of TB risk
Molecular tests	IL-13 and AIRE mRNA expression signature	Adults	Europe	[58–60]
	Elevated expression signatures of IFN response and T-cell genes	Infants with strong response to BCG vaccination	Africa	[115]
	Elevated expression signatures of inflammation, myeloid and glucose metabolism genes	Infants with weak response to BCG vaccination	Africa	[115]
Antigen-specific T-cells	Increased IFN-γ-expressing Ag85A-specific T-cells	Infants	Africa	[63]
	Increased Th1-cytokine-expressing BCG-specific CD4⁺ T-cells	Infants with strong response to BCG vaccination	Africa	[115]
Cell differentiation markers	Downmodulation of CD27 in CD4⁺ T-cells	Adults	Africa	[76]
Serum/plasma cytokine tests	Increased levels of IP-10	Adults	Africa	[86, 87]
Antigen-specific antibodies	Elevated levels of anti-Ag85A-binding IgG	Infants	Africa	[63]
Responses to latency antigens	IFN-γ response to in vitro stimulation of PBMCs using HBHA	Adults	Europe	[95]
Responses to latency antigens	IFN-γ response to in vitro stimulation of whole blood using Rv2628	Adults	Europe	[103]
CD8⁺ T-cell response	IFN-γ response to in vitro RD1 stimulation of PBMCs	Children and adults	Africa Europe	[37]

LTBI: latent TB infection; RD: region of difference; IGRA: interferon (IFN)-γ release assays; PPD: purified protein derivative; TST: tuberculin skin test; HLA-DR: D-related human leukocyte antigen; IL: interleukin; AIRE: autoimmune regulator; BCG: bacille Calmette–Guérin; Ag: antigen; Th: T-helper cell; IP: IFN-γ-inducible protein; Ig: immunoglobulin; PBMCs: peripheral blood mononuclear cells; HBHA: heparin-binding haemagglutinin.