Predikce klinického projevu reakce štěpu proti hostiteli po alogenní transplantaci kostní dřeně s využitím proteomických přístupů

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Title in English Prediction clinical manifestation of graft versus host disease after allogeneic bone marrow transplantation using proteomic approaches
Authors

KAPLANOVÁ Alexandra ZDRÁHAL Zbyněk KONEČNÁ Hana ŠEDO Ondrej MAYER Jiří POSPÍŠILOVÁ Šárka

Year of publication 2007
Type Conference abstract
MU Faculty or unit

Faculty of Medicine

Citation
Description Background: Acute graft versus host disease (GvHD) is a frequent complication of allogeneic stem cells transplantation (allo-SCT). The rapid diagnosis of acute GvHD following allo-SCT is important for optimizing the management of this life-threatening complication. Differentially expressed or excreted polypeptides and proteins have potential for early and accurate diagnosis of GvHD and other complications of allo-SCT. Aims: Search for blood plasma proteins useful as potential biomarkers for early detection of GvHD. Methods: 2-dimensional gel electrophoresis (2 DE) was used for separation of blood plasma proteins. Proteins considered as potential biomarkers for early prediction of GvHD were selected by image analysis. Protein spots with different expression levels were characterized by matrix-assisted laser desorption/ionization - time of flight mass spectrometry (MALDI-TOF-MS) using peptide mass fingerprinting. Samples of blood plasma, urine and lymphocytes, collected from the same patient before and after allo-SCT were analyzed. Analysed samples were collected at three time points: (1) approx. 10 days before GvHD manifestation, (2) approx. 2 days before GvDH manifestation and (3) during GvHD manifestation. Results: Proteomic analysis revealed several proteins differentially expressed during GvHD development. These potential biomarkers included serum natural proteinases (macroglobulin alpha2 and alpha1 anti-trypsin), components of complement (complement 4 binding protein and complement factor I), proteins of acute phase (haptoglobin, C-reactive protein and amyloid related serum protein (SAA)) and other proteins such as fibrin, fibrinogen, inter-alpha (globulin) inhibitor H4 and hemopexin precursor. Concentration of serum natural proteinases, haptoglobin, inter-alpha (globulin) inhibitor H4 and hemopexin precursor in blood plasma were significantly decreased in both samples collected prior to GvHD manifestation. In these samples was detected also slightly decreased expression of analyzed components of complement in comparison to samples collected during GvHD manifestation. On the other hand, expression of C-reactive protein and SAA was detected only 14 days before GvHD manifestation and these proteins completely disappeared 1 day before onset of disease and during its manifestation. Summary, Conclusions: These potential biomarkers could improve early prediction and treatment of GvHD and thereby reduce GvHD incidence and complications.
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