Graft-Versus-Host Disease: Can Biomarkers Assist in Differential Diagnosis, Prognosis, and Therapeutic Strategy?

Abstract

A crucial complication after allogeneic hematopoietic cell transplantation (alloHCT), namely, acute graft-versus-host disease (aGVHD), occurs in about 50% of transplant recipients, leading to high morbidity and mortality. Thus far, the diagnosis of GVHD has been mainly established through clinical features and histologic or laboratory evidence of periductal lymphocyte infiltration, fibroplasia, and mixed lymphocytic and plasmocytic inflammation. Intensive research is focused on identifying biomarkers for the early diagnosis, prediction of disease, response to treatment, prognosis, and risk stratification of patients. The serum biomolecules that have been investigated are reported and summarized. Moreover, oral tissue involvement in GVHD is described, and other biomarkers that have been proposed, such as saliva, are analyzed. Future research is highlighted as a necessity in order for these biomarkers to be validated and quantified for use in clinical practice.

Keywords: GVHD; biomarkers; saliva.

Figure 1

IL2-R-a: Interleukin 2 Receptor a; ST2: Suppressor of Tumorigenicity 2; HGF: Hepatocyte Growth Factor; TNFR-1: Tumor Necrosis Factor Receptor-1; Reg-3a: Regenerating Islet-Derived Protein 3a, a peptide found in Paneth cells of the intestines (the most validated GI aGVHD biomarker); TIM 3: T-cell Immunoglobulin Mucin Protein 3; Elafin: a serine protease inhibitor; sBAFF: Soluble B-Cell Activating Factor; CXCL9: Chemokine (C-X-C motif) Ligand 9; CXCL10: Chemokine (C-X-C motif) Ligand 10; DDK3: Dickkopf-Related Protein; MMP-3: Matrix Metalloproteinase 3; MMP-9: Matrix Metalloproteinase; OPN: Osteopontin; CD163: a scavenger receptor by activated monocytes/macrophages found in cases of oxidative stress. : Increased levels; : decreased levels.