A distinct evolution of the T-cell repertoire categorizes treatment refractory gastrointestinal acute graft-versus-host disease

作者：Meyer Everett H; Hsu Andro R; Liliental Joanna; Loehr Andrea; Florek Mareike; Zehnder James L; Strober Sam; Lavori Philip; Miklos David B; Johnson David S; Negrin Robert S^*

来源：Blood, 2013, 121(24): 4955-4962.

DOI：10.1182/blood-2013-03-489757

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.

• 出版日期2013-6-13