title: Predicting posttransplantation diabetes mellitus by regulatory T-cell phenotype: implications for metabolic intervention to modulate alloreactivity.
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 α(4)β(7)(+) (gut-homing) Tregs was increased (17.9% vs 10.7%; P = .048). In multivariate analysis, patients with PTDM continued to demonstrate elevated ratios of α(4)β(7)(+) 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.
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Engelhardt
authors.forename: Shubhada M
authors.initials: SM
authors.lastname: Jagasia
authors.forename: James E
authors.initials: JE
authors.lastname: Crowe
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Griffith
authors.forename: Bipin N
authors.initials: BN
authors.lastname: Savani
authors.forename: Adetola A
authors.initials: AA
authors.lastname: Kassim
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Lu
authors.forename: Jörn-Hendrik
authors.initials: JH
authors.lastname: Weitkamp
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Moore
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Yoder
authors.forename: Michael T
authors.initials: MT
authors.lastname: Rock
authors.forename: Madan
authors.initials: M
authors.lastname: Jagasia
mesh_terms: D000328:Adult; D000368:Aged; D003920:Diabetes Mellitus / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D005260:Female; D005434:Flow Cytometry; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011183:Postoperative Complications / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D011237:Predictive Value of Tests; D011379:Prognosis; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000378:metabolism*; D013997:Time Factors; D014184:Transplantation, Homologous; D055815:Young Adult