title: Tolerance associated gene expression following allogeneic hematopoietic cell transplantation.
abstract: Biologic markers of immune tolerance may facilitate tailoring of immune suppression duration after allogeneic hematopoietic cell transplantation (HCT). In a cross-sectional study, peripheral blood samples were obtained from tolerant (n = 15, median 38.5 months post-HCT) and non-tolerant (n = 17, median 39.5 post-HCT) HCT recipients and healthy control subjects (n = 10) for analysis of immune cell subsets and differential gene expression. There were no significant differences in immune subsets across groups. We identified 281 probe sets unique to the tolerant (TOL) group and 122 for non-tolerant (non-TOL). These were enriched for process networks including NK cell cytotoxicity, antigen presentation, lymphocyte proliferation, and cell cycle and apoptosis. Differential gene expression was enriched for CD56, CD66, and CD14 human lineage-specific gene expression. Differential expression of 20 probe sets between groups was sufficient to develop a classifier with > 90% accuracy, correctly classifying 14/15 TOL cases and 15/17 non-TOL cases. These data suggest that differential gene expression can be utilized to accurately classify tolerant patients following HCT. Prospective investigation of immune tolerance biologic markers is warranted.
authors.affiliation: Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, FL, United States of America.
authors.forename: Joseph
authors.initials: J
authors.lastname: Pidala
authors.affiliation: Bioinformatics, Moffitt Cancer Center, Tampa, FL, United States of America.
authors.forename: Gregory C
authors.initials: GC
authors.lastname: Bloom
authors.affiliation: Bioinformatics, Moffitt Cancer Center, Tampa, FL, United States of America.
authors.forename: Steven
authors.initials: S
authors.lastname: Eschrich
authors.affiliation: Department of Surgery, UCSF School of Medicine, San Francisco, CA, United States of America.
authors.forename: Minnie
authors.initials: M
authors.lastname: Sarwal
authors.affiliation: Molecular Genomics, Moffitt Cancer Center, Tampa, FL, United States of America.
authors.forename: Steve
authors.initials: S
authors.lastname: Enkemann
authors.affiliation: Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, FL, United States of America.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Betts
authors.affiliation: Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, FL, United States of America.
authors.forename: Francisca
authors.initials: F
authors.lastname: Beato
authors.affiliation: Molecular Genomics, Moffitt Cancer Center, Tampa, FL, United States of America.
authors.forename: Sean
authors.initials: S
authors.lastname: Yoder
authors.affiliation: Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, FL, United States of America.
authors.forename: Claudio
authors.initials: C
authors.lastname: Anasetti
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D019070:Cell Lineage / Q000276:immunology; D003430:Cross-Sectional Studies; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D014184:Transplantation, Homologous / Q000009:adverse effects