Program: Oral and Poster Abstracts
Session: 722. Clinical Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution: Poster II
Methods: From 2011 to 2014, 14 patients with TMA were enrolled into the study in a single medical center. 71 other patients following HSCT were recruited as control subjects including 11 cases of hepatic vein occlusion disease (VOD), 20 cases of severe infections, 20 cases of severe II-IV° GVHD and 20 cases without complications. Blood sample was collected before transplantation and at the onset of transplantation related complication. Fluorescence resonance energy transfer substrate (FRETS)-VWF73 assay detected plasma ADAMTS13 activity. Collagen-binding assay and latex immunoassay determined VWF activity and VWF antigen, respectively. Plasma VWF multimer was determined by agarose gel electrophoresis and Western blot. Plasma levels of complement C3b and C5b were measured with ELISA.
Results: Compared with the levels before transplantation, plasma ADAMTS13 activity and VWF antigen or activity in the patients with TMA did not differ from those who developed TMA, with infection or GVHD or without any complication (p > 0.05). However, plasma ADAMTS13 activity decreased and the ratio of VWF antigen/activity increased significantly in patients with VOD (p < 0.05). Plasma VWF multimer distribution was similar in patients with infection, GVHD or without complication, but ultralarge multimers of VWF was present in patients with TMA and VOD. Plasma levels of complement C3b was increased in patients after HSCT (198.46 ng/ml ±14.78 ng/ml) compared with healthy subjects (85.02 ng/ml±8.50ng/ml) (p < 0.05), but exhibited no difference in the other groups. Plasma C3b increased significantly in patients with TMA and GVHD (p<0.05). The plasma levels of C3b were higher in the TMA group (480.70 ng/ml±66.76ng/ml) than the GVHD group (298.50 ng/ml ±32.06 ng/) (p < 0.05). Also, plasma levels of C5b in patients with TMA were significantly increased (1059.49 ng/ml ±85.57 ng/ml) as compared with those before transplantation (653.19ng/ml ±44.91ng/ml) and other groups (p < 0.05).
Conclusions: We conclude that plasma ADAMTS 13 activity and the ratio of VWF antigen/activity remained stable in the patients with transplant-associated TMA, but the levels of complement C3b and C5b, particularly the C5b, increased significantly, suggesting the critical role of complement pathway in the pathogenesis of TMA. C5b may be a specific biomarker for early diagnosis of TMA but C3b is a marker for both TMA and GVHD.
Disclosures: No relevant conflicts of interest to declare.
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