Clinical Significance And Mechanism Of Stem Cell Transplantation In Patients With Serum Anti-endothelial Cell Antibodies Allogeneic

Abstract:Anti-endothelial cell antibody (AECA) has been well known to reflect endothelial injury. Meanwhile, graft-versus-host disease (GVHD), a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT), is also closely associated with endothelial injury. We assume that AECA might be associated with GVHD. To investigate the clinical significance of AECA in allo-HSCT recipients with GVHD, we detected AECA by cyto-enzyme linked immunosorbent assay (cyto-ELISA) in allo-HSCT recipients with acute and/or chronic GVHD (aGVHD and cGVHD), with small vascular endothelial cell line HMEC-1and large vessel endothelial cell line EA.hy926as substrate, respectively. Incidences of anti-HMEC-1AECA (anti-HMEC) and anti-EA.hy926AECA (anti-EAHY) were significantly higher in patients with grade II-IV than grade0-1aGVHD (42.9vs.20.7%, P=0.049;52.4vs.22.4%, P=0.011, respectively). There was no difference of incidences of AECA between patients with or without cGVHD. Patients with anti-EAHY positive results early post transplant demonstrated a higher incidence of cGVHD (59.6±1.4vs.33.4±0.5%, P=0.044). In patients with grade0-1aGVHD, AECA positive patients had higher overall survival (OS) and disease free survival (DFS)(P<0.05), and tended to have lower incidences of relapse and transplant related mortality (TRM). Our data suggested that AECA played an important role in the pathogenesis of GVHD. Abstract:During the procedure of allogeneic hematopoietic stem cell transplantation (allo-HSCT), endothelial injury is a critical pathogenesis of graft-versus-host disease (GVHD). Our previous work demonstrated that incidence of anti-endothelial cell antibody (AECA) was closely correlated with severity of acute GVHD, but the underlying mechanism of AECA remained unclear. To clarify the role of AECA in the pathogenesis of GVHD, we purified immunoglobulin (IgG) from sera of allo-HSCT recipients and incubated with human umbilical vein vascular endothelium (HUVEC) in vitro, then tested the functional changes and cell apoptosis. After incubation with AECA positive IgG, soluble adhesion molecules (sICAM-1and sVCAM-1) and clotting activity factors (vWF and TM) significantly elevated in culture supernatant (P <0.05), but inflammatory factors (IL-1β,IL-6, IL-8and ANG2) were not different from AECA negative samples (P>0.05). Additionally, AECA from AECA positive samples did not induce apoptosis. Our investigation demonstrates that AECA from allo-HSCT recipients dysregulates ECs’ function in vitro, and is of importance to reveal AECA and endothelial injury in the pathophysiology of GVHD and other transplant-related complications after allo-HSCT.