Biology of chronic graft-vs-host disease: Immune mechanisms and progress in biomarker discovery

Table 3 Candidate biomarkers of chronic graft-vs-host disease¹

Gene/protein	Function	Biofluid3	Ref.
BAFF, soluble; BAFF/B cell ratio	Growth factor, promotes B cell expansion and activation	Blood	[59,60,77]
CXCL92	Chemokine produced by activated T cells	Blood	[51,79]
CD-13, soluble	Antigen presentation	Blood	[59]
C-reactive protein3	Acute phase protein	Blood	[12]
Cystatin B	Inhibitor of cathepsin proteases	Saliva	[80]
IL-1ra	Inhibitor of IL-1 receptor signaling	Saliva	[80]
IL-2R, soluble	IL-2 receptor, marker of activated T cells	Blood	[59,76]
IL-6	Pro-inflammatory Th2 cytokine	Blood	[42,75]
IL-10	Th2 cytokine	Blood	[73]
IL-15	Enhances anti-tumor function of CD8+ T cells	Blood	[78]
Lactoperoxidase	Anti-microbial enzyme	Saliva	[81]
Lactoferrin	Iron-binding glycoprotein	Saliva	[81]
MICA, soluble	Stimulates T cell activity via NKG2D receptor	Blood	[30]
TGF-β	Anti-inflammatory cytokine; stimulates activity of Tregs	Blood	[33]
TNF-α	Pro-inflammatory Th1 cytokine	Blood	[73-75]

¹This table only includes proteins identified in human biofluids. Antibodies are discussed in the text;

²Blood markers were measured in either plasma or serum isolated from peripheral blood, depending on the study. For saliva, whole unstimulated saliva collected from oral cGVHD patients was used;

³Increased CRP levels were especially associated with joint/fascia and skin involvement, compared to the non-cGVHD control group. cGVHD: Chronic graft-vs-host disease; BAFF: B-cell activating factor; CXCL: Chemokine (C-X-C motif) ligand; CD-13: Cluster of Differentiation molecule 13 (or aminopeptidase N); IL-1ra: Interleukin 1 receptor antagonist; IL-2R: Interleukin 2 receptor; MICA: MHC class I-related chain A; TGF-β: Transforming growth factor beta; TNF-α: Tumor necrosis factor alpha; CRP: C-reactive protein.