Potential Novel Biomarkers in Chronic Graft-Versus-Host Disease

Abstract

Prognostic, diagnostic or predictive biomarkers are urgently needed for assessment of chronic graft-versus-host disease (cGvHD), a major risk for patients undergoing allogeneic hematopoietic stem cell transplantation. The main goal of this review generated within the COST Action EUROGRAFT “Integrated European Network on Chronic Graft Versus Host Disease” was to identify potential novel biomarkers for cGvHD besides the widely accepted molecular and cellular biomarkers. Thus, the focus was on cellular biomarkers, alloantibodies, glycomics, endothelial derived particles, extracellular vesicles, microbiome, epigenetic and neurologic changes in cGvHD patients. Both host-reactive antibodies in general, and particularly alloantibodies have been associated with cGvHD and require further consideration. Glycans attached to IgG modulate its activity and represent a promising predictive and/or stratification biomarker for cGVHD. Furthermore, epigenetic changes such as microRNAs and DNA methylation represent potential biomarkers for monitoring cGvHD patients and novel targets for developing new treatment approaches. Finally, the microbiome likely affects the pathophysiology of cGvHD; bacterial strains as well as microbial metabolites could display potential biomarkers for dysbiosis and risk for the development of cGvHD. In summary, although there are no validated biomarkers currently available for clinical use to better inform on the diagnosis, prognosis or prediction of outcome for cGvHD, many novel sources of potential markers have shown promise and warrant further investigation using well characterized, multi-center patient cohorts.

Profiling Tissue and Biofluid miR-155-5p, miR-155*, and miR-146a-5p Expression in Graft vs. Host Disease

“…It has been shown EVs from both non-immune and immune cells have important roles in immune regulation (8). The role of EVs in the pathophysiology of immunological disorders, including GvHD, is an exciting field of research, as EVs offer importance as prospective therapeutic targets, informative biological agents and predictive disease biomarkers (9). MiR-155 has been directly implicated in the control of immunity, by modulating both the adaptive and innate immune response (10).…”

Practice patterns in chronic graft-versus-host disease patient management and patient reported outcome measures across the EBMT allogeneic transplantation network

“…Our survey illustrates the current trends in cGvHD management and use of PROs in alloHSCT centers across the EBMT and COST Action EUROGRAFT network, highlighting a high uptake of NIH criteria in routine practice, going beyond the initial evaluation of Duarte et al [ 5 ]. Despite recent advances in the field [ 6 ], the use of biomarkers and cellular therapies for cGvHD remain modest. Finally, while already 17% of replying centers indicated the use of PRO´s in clinical routine, their integration in clinical care should be promoted based on current recommendations indicating their validity in including the patient’s perspective in transplantation outcome evaluation [ 7 – 9 ].…”

Exploring the Extracellular Vesicle MicroRNA Expression Repertoire in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis Treated with TNF Inhibitors

“…The most common practice is to employ microarray profiling to analyse a wide range of microRNAs on a qRT-PCR instrument [ 49 ]. However, a novel technique, NanoString, described previously in a study on serum miRNAs in patients with graft-versus-host disease (GvHD) [ 33 , 50 ], allows analysis of around 800 microRNAs using digital barcoding technology. This removes the need for reverse transcription or preamplification of RNA, as the technology is able to directly count isolated microRNA molecules.…”