Blood Journal
Leading the way in experimental and clinical research in hematology

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

  1. Everett H. Meyer1,
  2. Andro R. Hsu2,
  3. Joanna Liliental3,
  4. Andrea Löhr2,
  5. Mareike Florek1,
  6. James L. Zehnder4,
  7. Sam Strober5,
  8. Philip Lavori6,
  9. David B. Miklos1,
  10. David S. Johnson2, and
  11. Robert S. Negrin1,*
  1. 1 Division of Blood and Marrow Transplantation, Department of Medicine, Stanford University School of Medicine, Stanford, CA, United States;
  2. 2 GigaGen Inc., San Francisco, CA, United States;
  3. 3 Translational Research and Applied Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, United States;
  4. 4 Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, United States;
  5. 5 Division of Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, United States;
  6. 6 Biostatistics Division, Department of Health Research and Policy, Stanford University, Stanford, CA, United States
  1. * Corresponding author; email: negrs{at}stanford.edu

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.

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) 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.