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

Everett H. Meyer, Andro R. Hsu, Joanna Liliental, Andrea Löhr, Mareike Florek, James L. Zehnder, Sam Strober, Philip Lavori, David B. Miklos, David S. Johnson, Robert S. Negrin

Key points

  • T cell clones identified in the GI tract of patients with steroid-refractory acute GI GVHD expand in the blood with disease progression.

  • The T cell repertoire in the GI tract of steroid-refractory patients at the time of diagnosis is more similar than for responsive patients.


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) CDR3 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 eight primary-therapy responsive patients. Tracking GI clones identified at endoscopy longitudinally 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.

  • Submitted March 13, 2013.
  • Accepted April 20, 2013.