Abstract
BackgroundGastrointestinal acute graft-versus-host disease (GI aGVHD) is a lethal complication following allogeneic hematopoietic stem cell transplantation (HSCT). However, it is still very difficult to make a diagnosis of GI aGVHD in practice. To date, no consensus plasma biomarker of GI aGVHD can be used to help make a diagnosis. Here, we attempted to identify GI aGVHD associated plasma proteins in murine model, which can help make a diagnosis of GI aGVHD.MethodsWe used 8-plex isobaric tags for relative and absolute quantitation (8-plex iTRAQ) to screen out proteins in plasma samples taken from murine models before and after allogeneic HSCT. Next mRNA expressions were validated by quantitative real-time polymerase chain reaction in mouse intestinal epithelial samples.ResultsWe found that five proteins were increased at least 2-fold in the allogeneic group at day 7 compared with days 0, 3 and 15 (after Cyclosporin A treatment) and the syngeneic group at day 7. These 5 proteins were VNN3, ZNF746, C4BP, KNG1 and FETUB, and they were consistent with results from negative labeling with 8-plex iTRAQ. Furthermore, increase in mRNA level of VNN3 was confirmed in murine intestinal epithelial samples with aGVHD.ConclusionsOur results demonstrate that plasma VNN3 protein is associated with GI aGVHD in murine model.
Highlights
Gastrointestinal acute graft-versus-host disease (GI Acute graft-versus-host-disease (aGVHD)) is a lethal complication following allogeneic hematopoietic stem cell transplantation (HSCT)
The aGVHD scores of allogeneic transplantation mice differed from the scores of the syngeneic transplantation mice; the gap between the aGVHD scores in the allogeneic and syngeneic groups was largest at day 7 (P < 0.001) (Fig. 1a and b)
We identified and quantified 712 proteins of which 5 were increased at least 2-fold in the allogeneic group at day 7 compared with days 0, 3 and 15 and the syngeneic group at day 7 (Additional file 2)
Summary
Gastrointestinal acute graft-versus-host disease (GI aGVHD) is a lethal complication following allogeneic hematopoietic stem cell transplantation (HSCT). No consensus plasma biomarker of GI aGVHD can be used to help make a diagnosis. We attempted to identify GI aGVHD associated plasma proteins in murine model, which can help make a diagnosis of GI aGVHD. Acute graft-versus-host-disease (aGVHD), a lethal complication after allogeneic hematopoietic stem cell transplantation (allo HSCT), contributes to high nonrelapse mortality [1]. A diagnosis of GI aGVHD is traditionally based on clinical manifestations and endoscopic biopsy [3]. McDonald’s group used several proteins to predict severe GI aGVHD and non-relapse mortality, such as T-cell immunoglobulin and mucin-domain containing-3, soluble tumor necrosis factor-alpha, interleukin 1 receptor-like 1 and interleukin −6 [8].
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