Table 2.

Candidate aGVHD biomarkers identified by proteomics.

Protein	Study	Biofluid Sources	No. of patients in studies	Function(s)	Role in aGVHD
Peptides Sets	Kaiser 200466, Srinivasan 200657	Urine	45	Spectral profiles of peptides involved in aGVHD were identified.	Identification of the peptides present in the proteome during aGVHD (e.g. leukotriene A4 hydrolase, albumin, collagen α chain I, and collagen α1 chain III)
		Serum	34
	Imanguli 200758	Saliva	41
	Weissinger 2007125		175
Biomarker panel of four proteins: IL-2Rα, TNFR1, IL-8, HGF	Paczesny 200954	Plasma	424	See Table 1 for individual cytokine functions.	Diagnose aGVHD in patients at onset of clinical symptoms with AUC of 0.91 in training set and 0.86 in validation set. Also provide prognostic information including long term survival.
CCL8	Hori 2008118	Serum	14	Major chemoattractant for dendritic cells, monocytes, and activated T cells.	Serum concentration correlates with aGVHD severity.
Elafin	Paczesny 201065	Plasma	522	Elastase inhibitor overexpressed in inflamed epidermis in response to IL-1 and TNFα.	Produced by keratinocytes. Increased concentrations at onset of skin aGVHD. Correlates with the severity and mortality of skin aGVHD.
REG3α	Ferrara 201164	Plasma	1034	Antimicrobial protein secreted by Paneth cells to protect the epithelial barrier function of the intestinal mucosa.	Released into circulation via GVHD-induced breaches of the mucosal intestinal barrier. Elevated in GI-GVHD and correlates to nonrelapse mortality.
ST2 (IL-33 Rc)	Vander Lugt 201391	Plasma	1054	Receptor for IL-33; effector molecule of Th2 responses. Soluble form acts as decoy receptor for interleukin-33, driving Th2 cells toward a Th1-cell phenotype.	Increased levels at therapy initiation correlate with treatment unresponsiveness and mortality. Levels early post-transplantation (day 14) are associated with increased risk for death.