Change in serum proteome during allogeneic hematopoietic stem cell transplantation and clinical significance of serum C-reactive protein and haptoglobin

Abstract

Successful hematopoietic stem cell transplantation (HSCT) involves the restoration of hematopoietic function after engraftment, arising from the differentiation and proliferation of hematopoietic stem cells. Several factors could influence the course of allogeneic-HSCT (allo-HSCT). Therefore, knowledge of serum proteome changes during the allo-HSCT period might increase the efficacy of diagnosis and disease prevention efforts. This study conducted proteomic analyses to find proteins that were significantly altered in response to allo-HSCT. Sera from five representative patients who underwent allo-HSCT were analyzed by 2-dimensional gel electrophoresis and liquid chromatography tandem mass spectrometry, and were measured on a weekly basis before and after allo-HSCT in additional 78 patients. Fourteen protein spots showing changes in expression were further examined, and most proteins were identified as acute phase proteins (APPs). Studies of 78 additional patients confirmed that C-reactive protein (CRP) and haptoglobin undergo expression changes during allo-HSCT and thus may have the potential to serve as representative markers of clinical events after allo-HSCT. Maximal CRP level affected the development of major transplant-related complications (MTCs) and other problems such as fever of unknown origin. Particularly, an increase in CRP level 21 days after allo-HSCT was found to be an independent risk factor for MTC. Maximal haptoglobin and haptoglobin level 14 days after allo-HSCT were predictive of relapses in underlying hematologic disease. Our results indicated that CRP and haptoglobin were significantly expressed during allo-HSCT, and suggest that their level can be monitored after allo-HSCT to assess the risks of early transplant-related complications and relapse.

Discovery of the serum biomarker proteins in severe preeclampsia by proteomic analysis

“…In this analysis, the collected serum samples were treated using a multiple affinity removal column (MARS) containing six antibodies against albumin, IgG, IgA, transferrin, haptoglobin, and alpha-1-antitrypsin (Ryu et al, 2010). After high abundant protein depletion, the serum samples were digested using a sequence grade trypsin for LC-MS/MS analysis to compare the serum proteomes from women with PE and those from women undergoing normal pregnancy.…”

Diagnostic and risk criteria for HSCT-associated thrombotic microangiopathy: a study in children and young adults

“…The haptoglobin level was actually higher among subjects with TMA who died, possibly indicating its reflection as a marker of inflammation. [30][31][32] Therefore, the absence of a low haptoglobin should not exclude consideration of the diagnosis of TMA in HSCT recipients. These factors may be due to an earlier recognition of the TMA symptoms in this study given the systematic and careful monitoring of subjects, but it could also indicate that HSCT-associated TMA is a different and distinct disease from atypical hemolytic uremic syndrome and other disorders that share features of complement dysregulation.…”

Small vessels, big trouble in the kidneys and beyond: hematopoietic stem cell transplantation–associated thrombotic microangiopathy

“…65 Finally, the diagnosis of TA-TMA may be masked by other phenomena occurring after HSCT, such as haptoglobin changes secondary to inflammation or Coombs-positive hemolytic anemia. 66 Current guidelines do not include elevation of blood pressure, which is an easily measured and clinically important indicator of renal dysfunction in TA-TMA. 60 Although hypertension may be multifactorial after allogeneic HSCT, we identified elevated blood pressure as an early marker of TA-TMA in pediatric patients with neuroblastoma undergoing autologous HSCT, who have a lower risk of hypertension than patients who received allogeneic transplants.…”