Biomarkers associated with occurrence and severity of graft-versus-host disease

The application of allogenic hematopoietic stem cell transplantation (HSCT) is limited by life-threatening complications such as severe or acute graft-versus-host disease (GvHD). Despite intensive prophylaxis with immunosuppressive agents, the incidence of GvHD occurs in 9-50% of patients undergoing transplant with an identical HLA sibling matched donor and 75% of patients undergoing unrelated HLA donors. Currently, diagnosis of GvHD is based mainly on evaluation of clinical symptoms including skin rash, diarrhoea and elevation of serum liver enzymes. To date, no validated biomarkers have been established for chronic GVHD, although several candidate biomarkers have been identified. The aim of this study was to characterize a number of candidate biomarkers in the serum of patients pre and post HSCT with and without GvHD. Expression of the biomarkers were also analysed using the skin explant model. Blood samples were collected from patients during pre-conditioning therapy (7 days prior to HSCT) and at 0, 14, 28 days 3,6,12 months post transplant. From the nine candidate biomarkers (BAFF, IL-33, hTLA1, APRIL, Omentin, RANKL, OPG, NALP3, NALP1) tested, the results identified two molecules, BAFF and IL-33 as potential GvHD markers which may be suitable for potential disease management. BAFF (B cell activation factor) is a key regulator of B cell homeostasis and is also involved in regulation of T cell function. BAFF has been shown to be elevated in autoimmune disorders and in cGvHD patients. Likewise, our results showed serum BAFF levels were significantly higher in patients with extensive cGvHD (p