Journal
BLOOD
Volume 121, Issue 24, Pages 4955-4962Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2013-03-489757
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Funding
- National Institutes of Health, National Cancer Institute [P01 CA049605]
- American Society for Blood and Marrow Transplantation Young Investigator award
- Stanford Translational and Applied Medicine Pilot grant (Stanford Department of Medicine)
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Steroid refractory gastrointestinal (GI) acute graft-versus-host disease (aGVHD) is a major cause of mortality in hematopoietic stem cell transplantation (HCT) without immune markers to establish a diagnosis or guide therapy. We found that T-cell receptor beta (TCR beta) complementarity-determining region 3 repertoire sequencing reveals patterns that could eventually serve as a disease biomarker of T-cell alloreactivity in aGVHD. We identified T-cell clones in GI biopsies in a heterogeneous group of 15 allogeneic HCT patients with GI aGVHD symptoms. Seven steroid-refractory aGVHD patients showed a more conserved TCR beta clonal structure between different biopsy sites in the GI tract than 8 primary therapy-responsive patients. Tracking GI clones identified longitudinally at endoscopy in the blood also revealed an increased clonal expansion in patients with steroid-refractory disease. Immune repertoire sequencing-based methods could enable a novel personalized way to guide diagnosis and therapy in diseases where T-cell activity is a major determinant.
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