title: A distinct evolution of the T-cell repertoire categorizes treatment refractory gastrointestinal acute graft-versus-host disease.
abstract: 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 β (TCRβ) 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 TCRβ 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.
authors: Division of Blood and Marrow Transplantation, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors: Everett H
authors: EH
authors: Meyer
authors: Andro R
authors: AR
authors: Hsu
authors: Joanna
authors: J
authors: Liliental
authors: Andrea
authors: A
authors: Löhr
authors: Mareike
authors: M
authors: Florek
authors: James L
authors: JL
authors: Zehnder
authors: Sam
authors: S
authors: Strober
authors: Philip
authors: P
authors: Lavori
authors: David B
authors: DB
authors: Miklos
authors: David S
authors: DS
authors: Johnson
authors: Robert S
authors: RS
authors: Negrin
mesh_terms: D000328:Adult; D000368:Aged; D022801:Complementarity Determining Regions / Q000235:genetics* / Q000276:immunology; D005260:Female; D005767:Gastrointestinal Diseases / Q000175:diagnosis / Q000209:etiology / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000209:etiology / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D019337:Hematologic Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology; D012720:Severity of Illness Index; D014184:Transplantation, Homologous
chemical_list: D022801:Complementarity Determining Regions; D016693:Receptors, Antigen, T-Cell, alpha-beta
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