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Updated: Jul 27, 2026

High Throughput Sequential ELISA for Validation of Biomarkers of Acute Graft-Versus-Host Disease
Published on: October 31, 2012
The proteome pattern cGvHD_MS14 allows early and accurate prediction of chronic GvHD after allogeneic stem cell
E M Weissinger1, C Human1, J Metzger2
1Department of Hematology, Hemostasis, Oncology and Stem cell transplantation, Hannover Medical School, Hannover, Germany.
Insights
A new urinary proteome pattern (cGvHD_MS14) can predict chronic graft-versus-host disease (cGvHD) years after stem cell transplantation. This biomarker offers early, sensitive, and specific detection, aiding timely therapeutic intervention.
Area of Science:
- Biochemistry
- Immunology
- Oncology
Background:
- Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy but carries risks.
- Chronic graft-versus-host disease (cGvHD) significantly contributes to morbidity and mortality post-allo-HSCT.
- Current cGvHD diagnosis relies on clinical features and biopsies, often leading to delayed detection.
Purpose of the Study:
- To develop and validate a urinary proteome-pattern (cGvHD_MS14) for predicting cGvHD onset and severity.
- To establish an unbiased laboratory test for early cGvHD detection.
- To improve diagnostic accuracy and enable earlier therapeutic interventions.
Main Methods:
- Generation of a urinary cGvHD-specific proteome-pattern (cGvHD_MS14) using capillary electrophoresis-mass spectrometry.
- Prospective evaluation of cGvHD_MS14 on samples from 412 patients across four transplant centers.
- Development of a logistic regression model combining cGvHD_MS14 with clinical variables.
Main Results:
- cGvHD_MS14 demonstrated 84% sensitivity and 76% specificity for cGvHD classification.
- Combining cGvHD_MS14 with clinical variables increased sensitivity to 93%.
- cGvHD was predicted up to 55 days prior to clinical diagnosis; acute GvHD was not detected.
Conclusions:
- The cGvHD_MS14 proteome pattern enables early, sensitive, and specific prediction of cGvHD.
- This biomarker can serve as an independent diagnostic criterion, potentially facilitating earlier treatment.
- Further research into the identified peptides may elucidate cGvHD pathogenesis.
Abstract:
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be curative, but is associated with significant morbidity and mortality. Chronic graft-versus-host disease (cGvHD), characterized by inflammation and fibrosis of multiple target organs, considerably contributes to the morbidity and mortality even years after allo-HSCT. Diagnosis of cGvHD is based on clinical features and histology of biopsies. Here, we report the generation of a urinary cGvHD-specific proteome-pattern (cGvHD_MS14) established by capillary electrophoresis-mass spectrometry to predict onset and severity of cGvHD as an unbiased laboratory test. cGvHD_MS14 was evaluated on samples from 412 patients collected prospectively in four transplant centers. Sensitivity and specificity was 84 and 76% by cGvHD_MS14 classification. Sensitivity further increased to 93% by combination of cGvHD_MS14 with relevant clinical variables to a logistic regression model. cGvHD was predicted up to 55 days prior to clinical diagnosis. Acute GvHD is not recognized by cGvHD_MS14. cGvHD_MS14 consists of 14 differentially excreted peptides, six of those have been sequenced to date and are fragments from thymosin β-4, eukaryotic translation initiation factor 4γ2, fibrinogen β-chain or collagens. In conclusion, the cGvHD_MS14-pattern allows early, highly sensitive and specific prediction of cGvHD as an independent diagnostic criterion of clinical diagnosis potentially allowing early therapeutic intervention.
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