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High Throughput Sequential ELISA for Validation of Biomarkers of Acute Graft-Versus-Host Disease
Published on: October 31, 2012
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B cells in chronic graft-versus-host disease
William McManigle1, Ayman Youssef2, Stefanie Sarantopoulos3
1Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University, Durham, NC, USA; Department of Medicine, Duke University, Durham, NC, USA.
Human Immunology
|March 9, 2019
Summary
Chronic graft-versus-host disease (cGVHD) involves B cells and B Cell Activating Factor (BAFF). Targeting B cell signaling pathways, like Syk and BTK, may restore B cell balance after allogeneic stem cell transplantation.
Area of Science:
- Immunology
- Hematology
- Oncology
Background:
- Allogeneic hematopoietic stem cell transplantation (alloHCT) treats hematologic diseases but risks graft-versus-host disease (GVHD).
- Chronic GVHD (cGVHD) is a significant cause of late morbidity and mortality post-alloHCT.
- B cells play a key role in cGVHD pathogenesis, evidenced by responses to rituximab.
Purpose of the Study:
- Investigate the role of B cell homeostasis and signaling in cGVHD.
- Explore the impact of B Cell Activating Factor (BAFF) on B cell activation in cGVHD.
- Evaluate small molecule inhibitors targeting B cell signaling pathways (Syk, BTK) for cGVHD treatment.
Main Methods:
- Analysis of peripheral B cell homeostasis and BAFF levels in cGVHD patients.
- Assessment of B cell signaling pathways, including BAFF-associated and B Cell Receptor (BCR) pathways.
- Utilizing murine models to confirm the role of Syk and BTK in cGVHD development.
Main Results:
- Altered B cell homeostasis and elevated BAFF levels are observed in cGVHD patients.
- Increased BAFF-to-B cell ratios correlate with constitutively activated B cells exhibiting enhanced survival.
- Hyper-activation of Syk and BTK signaling pathways in cGVHD B cells was identified.
Conclusions:
- B cells and their signaling pathways are critical in cGVHD.
- Targeting BAFF and BCR signaling molecules like Syk and BTK offers potential therapeutic strategies.
- Restoring B cell homeostasis via small molecule inhibitors may improve outcomes for cGVHD patients.
Keywords:
Allogeneic hematopoietic stem cell transplantation (AlloHCT)Autologous hematopoietic stem cell transplantation (autoHCT)B cell activation factor (BAFF)B cell linker (Blnk) proteinB cell receptor (BCR)B cellsChronic graft-versus-host disease (cGVHD)Graft-versus-host disease (GVHD)Spleen tyrosine kinase (Syk) proteinMore Related Videos
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