Proteomics for hematopoietic stem cell transplantation

ABSTRACT

Introduction: After the genomic era, the analysis of the proteome has gained increasing importance. Peptides and/or proteins present in tissue or body fluids can depict health and are prone to change during disease, not only in configuration but also in abundance. Early on, high throughput proteome analysis was implemented in the diagnostic of therapy-linked or induced complications arising after allogeneic hematopoietic stem cell transplantation (HSCT). Several proteomic approaches are currently used in the prediction or diagnosis of acute and/or chronic graft-versus-host disease (GvHD).

Areas covered: This review will report on two high throughput proteomics technologies used in the clinical setting to date, namely enzyme-linked-immunosorbent assays (ELISA) for key proteins involved in the pathogenesis of acute GvHD and on capillary electrophoresis coupled on-line to mass spectrometry (CE-MS). Here, we summarize the current data and discuss the strength as well as the limitations of each method and compare the usefulness and practicability in the post-HSCT setting for prediction and diagnosis of acute GvHD.

Expert commentary: Both technologies are applied in the clinic and have been tested on several hundred patients after HSCT. The data from both technologies may complement each other in diagnosis of GvHD.

KEYWORDS:

• Clinical proteomics
• stem cell transplantation
• graft-versus-host disease
• biomarkers

Article highlights

• Identification of biomarkers for clinical use can be achieved application of high throughput analysis platforms such as mass spectrometry (e.g. CE-MS) or enzyme-linked immunosorbent assays.

• The application of CE-MS allows identifying new, unknown peptides that may be involved in the pathogenesis of GvHD.

• Proteins involved in the pathophysiology of GvHD can be used for risk stratification of patients after HSCT.

• Clinical trials testing the proteomic biomarkers for prediction/prognosis of GvHD are currently ongoing in Europe, United States and in international consortia.

• The harmonization of biomarkers for clinical prediction/prognosis of GvHD should be the next goal to ensure best possible care for patients’ post-HSCT.

Declaration of interest

J. Metzger is an employee of Mosaiques Diagnostics. A. Ganser has served as an Advisory board member for Jazz Pharmaceuticals, Novartis and Celgene. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded in part by a grant provided by the German Ministry of Research and Education BMBF: grant number: 01KG0804.