Blood Journal
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Brief report
Predicting posttransplantation diabetes mellitus by regulatory T-cell phenotype: implications for metabolic intervention to modulate alloreactivity

  1. Brian G. Engelhardt1,
  2. Shubhada M. Jagasia1,
  3. James E. Crowe Jr2,3,
  4. Michelle L. Griffith1,
  5. Bipin N. Savani1,
  6. Adetola A. Kassim1,
  7. Pengcheng Lu4,
  8. Jörn-Hendrik Weitkamp2,
  9. Daniel J. Moore2,
  10. Sandra M. Yoder2,
  11. Michael T. Rock2, and
  12. Madan Jagasia1
  1. Departments of 1Medicine,
  2. 2Pediatrics,
  3. 3Pathology, Microbiology, and Immunology, and
  4. 4Biostatistics, Vanderbilt University Medical Center, Nashville, TN

Abstract

Chronic inflammation and decreased frequency of regulatory T cells (Tregs) in visceral adipose tissue contribute to the propagation of insulin resistance to diabetes mellitus. We tested the hypothesis that new-onset posttransplantation diabetes mellitus (PTDM) is associated with measurable changes in Treg subsets after allogeneic hematopoietic stem cell transplantation (HSCT). PTDM before day 100 and Treg phenotype at engraftment were determined in 36 HSCT recipients without preceding history of diabetes mellitus. Among patients with new-onset PTDM (N = 24), the frequency of circulating CLA+ (skin-homing) Tregs was decreased (1.53% vs 3.99%; P = .002) and the percentage of α4β7+ (gut-homing) Tregs was increased (17.9% vs 10.7%; P = .048). In multivariate analysis, patients with PTDM continued to demonstrate elevated ratios of α4β7+ Tregs to CLA+ Tregs (odds ratio, 18.1; P = .020). PTDM is associated with altered immune regulation after HSCT and could represent a target to modulate alloreactivity.

  • Submitted October 7, 2011.
  • Accepted January 6, 2012.
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