B-cell activating factor (BAFF) plasma level at the time of chronic GvHD diagnosis is a potential predictor of non-relapse mortality

Saliba, Rima M.; Sarantopoulos, Stefanie; Kitko, Carrie L.; Pawarode, Attaphol; Goldstein, Steven C.; Magenau, John; Alousi, Amin M.; Churay, Tracey; Justman, Holly A.; Paczesny, Sophie; Reddy, Pavan; Couriel, Daniel R.

doi:10.1038/bmt.2017.73

Cited by 24 publications

(19 citation statements)

References 36 publications

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“…c High levels of soluble B-cell-activating factor and the balance of B-cell subsets during B-cell reconstitution were the first biomarkers correlated with cGVHD. 42,82,83 c Prolonged imbalance of CD4 1 CD25 1 FOXP3 1 Tregs vs conventional CD4 1 T cells post-HSCT was associated with a loss of tolerance and significant cGVHD manifestations. 40,84 c Using a quantitative proteomics approach, a biomarker panel of 4 proteins (ST2, CXCL9, matrix metalloproteinase 3 [MMP-3], and osteopontin) showed significant correlation with cGVHD diagnosis.…”

Section: Cytomicsmentioning

confidence: 99%

Biomarkers for posttransplantation outcomes

Paczesny

2018

Blood

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During the last decade, the development of biomarkers for the complications seen after allogeneic hematopoietic stem cell transplantation has expanded tremendously, with the most progress having been made for acute graft-versus-host disease (aGVHD), a common and often fatal complication. Although many factors are known to determine transplant outcome (including the age of the recipient, comorbidity, conditioning intensity, donor source, donor-recipient HLA compatibility, conditioning regimen, posttransplant GVHD prophylaxis), they are incomplete guides for predicting outcomes. Thanks to the advances in genomics, transcriptomics, proteomics, and cytomics technologies, blood biomarkers have been identified and validated for us in promising diagnostic tests, prognostic tests stratifying for future occurrence of aGVHD, and predictive tests for responsiveness to GVHD therapy and nonrelapse mortality. These biomarkers may facilitate timely and selective therapeutic intervention. However, such blood tests are not yet available for routine clinical care. This article provides an overview of the candidate biomarkers for clinical evaluation and outlines a path from biomarker discovery to first clinical correlation, to validation in independent cohorts, to a biomarker-based clinical trial, and finally to general clinical application. This article focuses on biomarkers discovered with a large-scale proteomics platform and validated with the same reproducible assay in at least 2 independent cohorts with sufficient sample size according to the 2014 National Institutes of Health consensus on biomarker criteria, as well as on biomarkers as tests for risk stratification of outcomes, but not on their pathophysiologic contributions, which have been reviewed recently.

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Section: Cytomicsmentioning

confidence: 99%

Biomarkers for posttransplantation outcomes

Paczesny

2018

Blood

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“…In recent studies, B cell activating factor (BAFF) plasma levels were also correlated with the development and severity of cGVHD [11,[21][22][23]. BAFF, a member of the tumor necrosis factor family, is involved in the survival and maturation of peripheral B cells [24].…”

Section: Introductionmentioning

confidence: 99%

Double-Negative T Cell Levels Correlate with Chronic Graft-versus-Host Disease Severity

Hillhouse

Thiant

Moutuou

et al. 2019

Biology of Blood and Marrow Transplantation

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Chronic graft-versus-host disease (cGVHD) is a major complication, affecting 50% to 80% of long-term survivors of allogeneic hematopoietic stem cell transplantation. Current cGVHD therapies are neither specific nor curative, and patients are typically maintained for several months to years under immunosuppressive regimens that are associated with important side effects and increased susceptibility to life-threatening infections. As a result, continued investigation into the pathology of the disease and the search for novel diagnostic and therapeutic strategies to treat cGVHD remains a high priority. We report that the cellular dynamics of various immune cell subsets are related to cGVHD onset and severity in a cohort of allogeneic hematopoietic stem cell transplantation recipients. We document a decrease in the proportion of CD45RO CD4CD8 (double-negative [DN]) T cells at the onset of cGVHD, a time at which serum levels of B cell activating factor and B cells are increased. We also find that DN T cell levels are correlated with cGVHD severity. Our present findings are in line with the view that activated DN T cells exhibit their immunoregulatory potential by eliminating B cells in vivo. Taken together, these findings suggest that maintaining elevated DN T cell numbers before the onset of cGVHD may prevent pathological B cell responses.

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“…sBAFF was markedly elevated in cGVHD patients in two other studies [41,42]. More recently, another study demonstrated that increased levels of cGVHD can be essential for risk stratification as higher sBAFF at the time of diagnosis was associated with NRM [43]. …”

Section: Useful Cgvhd Biomarkersmentioning

confidence: 97%

The search for drug-targetable diagnostic, prognostic and predictive biomarkers in chronic graft-versus-host disease

Ren

Adom

Paczesny

2018

Expert Review of Clinical Immunology

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Introduction Chronic graft-versus-host disease (cGVHD) continues to be the leading cause of late morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT), which is an increasingly applied curative method for both benign and malignant hematologic disorders. Biomarker identification is crucial for the development of noninvasive and cost-effective cGVHD diagnostic, prognostic, and predictive test for use in clinic. Furthermore, biomarkers may help to gain a better insight on ongoing pathophysiological processes. The recent widespread application of omics technologies including genomics, transcriptomics, proteomics and cytomics provided opportunities to discover novel biomarkers. Areas covered This review focuses on biomarkers identified through omics that play a critical role in target identification for drug development, and that were verified in at least two independent cohorts. It also summarizes the current status on omics tools used to identify these useful cGVHD targets. We briefly list the biomarkers identified and verified so far. We further address challenges associated to their exploitation and application in the management of cGVHD patients. Finally, insights on biomarkers that are drug targetable and represent potential therapeutic targets are discussed. Expert commentary We focus on biomarkers that play an essential role in target identification.

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B-cell activating factor (BAFF) plasma level at the time of chronic GvHD diagnosis is a potential predictor of non-relapse mortality

Cited by 24 publications

References 36 publications

Biomarkers for posttransplantation outcomes

Biomarkers for posttransplantation outcomes

Double-Negative T Cell Levels Correlate with Chronic Graft-versus-Host Disease Severity

The search for drug-targetable diagnostic, prognostic and predictive biomarkers in chronic graft-versus-host disease

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