Idiopathic pulmonary fibrosis biomarkers: clinical utility and a way of understanding disease pathogenesis

Figures & data

Figure 1 Translation of a candidate biomarker into clinical practice.

Notes: When a candidate biomarker is identified, it should be easily measurable and mechanistically plausible. The candidate biomarker then enters a testing and validation phase. The candidate biomarker should undergo biologic testing to establish its role in the pathogenesis of disease. In parallel, the candidate biomarker is tested in patients in order to establish reproducibility, sensitivity, and specificity. Finally, during the implementation phase, the cost-effectiveness of the test should be established. This process should lead to both a biologically and clinically relevant biomarker.

Table 1 Summary of candidate biomarker data

Mechanistic category	Candidate biomarker	Predisposition	Diagnosis	Prognosis	Therapeutic monitoring
Alveolar epithelial cell damage/dysfunction	KL-6	–	−	++	+
	SP-A + SP-D	−	−	+	−
Extracellular signals	OPN	−	−	−	−
	vegf	−	±	+	+
Fibrogenesis/matrix remodeling	MMP7	−	+	++	−
	LOXL2	−	−	+	−
	Periostin	−	−	++	−
	Fibrocytes	−	−	+	−
Immune dysregulation/inflammation	CCL18	−	−	+	−
	YKL-40	−	−	+	±
	IL-8	−	+	++	−
	ICAM-1	−	−	++	−
T-cells	Sema7a	−	±	+	−
	CD28	−	−	++	−
B-cells and autoimmunity	anti-HSP70	−	−	+	−
	BLyS	−	+	+	−
	CXCL13	−	+	++	−
Genetic mutations	MUC5B	+	−	−	−
	Telomere shortening	+	−	−	−
	TOLLIP	+	−	+	−

Notes: The pathways reviewed in this manuscript are listed based on their proposed mechanistic category. We have rated the studies as follows: ++ denotes relatively strong evidence for the biomarker based on multiple studies or on large single studies; + denotes small single-study evidence for biomarker utility; ± denotes candidate biomarkers with equivocal evidence; – denotes candidate biomarkers without data.

Abbreviations: KL-6, Krebs von den Lungen 6; SP, surfactant protein; OPN, osteopontin; VEGF, vascular endothelial growth factor; MMP7, matrix metalloproteinase-7; LOXL2, lysyl oxidase-like 2; CCL18 chemokine (C-C motif) ligand 18; IL-8, interleukin-8; ICAM-1, intercellular adhesion molecule-1; Sema7a, semaphorin 7a; HSP70, heat shock protein 70; CXCL13, chemokine (C-X-C motif) ligand 13; MUC5B, Mucin 5B; TOLLIP, toll-interacting protein.