title: Allogeneic HY antibodies detected 3 months after female-to-male HCT predict chronic GVHD and nonrelapse mortality in humans.
abstract: Allogeneic antibodies against minor histocompatibility antigens encoded on the Y chromosome (HY-Abs) develop after hematopoietic cell transplant (HCT) of male recipients with female donors (F→M). However, the temporal association between HY-Ab development and chronic graft-versus-host disease (cGVHD) has yet to be elucidated. We studied 136 adult F→M HCT patients, with plasma prospectively collected through 3 years posttransplant, and measured immunoglobulin G against 6 H-Y antigens. Multiple HY-Abs were frequently detected beginning at 3 months posttransplant: 78 (57%) of F→M patients were seropositive for at least 1 of the 6 HY-Abs, and 3-month seropositivity for each HY-Ab was associated with a persistent seropositive response throughout the posttransplant follow-up period (P < .001 in each). There were no associations between pretransplant features and 3-month overall HY-Ab development. Detection of multiple HY-Abs at 3 months (represented by HY score) was significantly associated with an increased risk of cGVHD (P < .0001) and nonrelapse mortality (P < .01). Compared to clinical factors alone, the addition of HY score to clinical factors improved the predictive potential of cGVHD (P < .01). Monitoring HY-Ab development thus stratifies cGVHD risk in F→M HCT patients and may support preemptive prophylaxis therapy for cGVHD beginning at 3 months posttransplant.
authors.affiliation: Division of Blood and Marrow Transplantation, Department of Medicine and.
authors.forename: Hideki
authors.initials: H
authors.lastname: Nakasone
authors.affiliation: Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA;
authors.forename: Lu
authors.initials: L
authors.lastname: Tian
authors.affiliation: Division of Blood and Marrow Transplantation, Department of Medicine and.
authors.forename: Bita
authors.initials: B
authors.lastname: Sahaf
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; and.
authors.forename: Takakazu
authors.initials: T
authors.lastname: Kawase
authors.affiliation: Division of Blood and Marrow Transplantation, Department of Medicine and.
authors.forename: Kelsi
authors.initials: K
authors.lastname: Schoenrock
authors.affiliation: Division of Blood and Marrow Transplantation, Department of Medicine and.
authors.forename: Spenser
authors.initials: S
authors.lastname: Perloff
authors.affiliation: Division of Blood and Marrow Transplantation, Department of Medicine and.
authors.forename: Christine E
authors.initials: CE
authors.lastname: Ryan
authors.affiliation: Division of Blood and Marrow Transplantation, Department of Medicine and.
authors.forename: Jed
authors.initials: J
authors.lastname: Paul
authors.affiliation: Division of Blood and Marrow Transplantation, Department of Medicine and.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Popli
authors.affiliation: Division of Blood and Marrow Transplantation, Department of Medicine and.
authors.forename: Fang
authors.initials: F
authors.lastname: Wu
authors.affiliation: Division of Blood and Marrow Transplantation, Department of Medicine and.
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Otani
authors.affiliation: Stanford Functional Genomics Facility, Stanford University School of Medicine, Stanford, CA.
authors.forename: John
authors.initials: J
authors.lastname: Coller
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; and.
authors.forename: Edus H
authors.initials: EH
authors.lastname: Warren
authors.affiliation: Division of Blood and Marrow Transplantation, Department of Medicine and.
authors.forename: David B
authors.initials: DB
authors.lastname: Miklos
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D005260:Female; D006086:Graft vs Host Disease / Q000175:diagnosis* / Q000209:etiology* / Q000401:mortality; D006182:H-Y Antigen / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007518:Isoantibodies / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D063868:Patient Outcome Assessment; D011379:Prognosis; D040901:Proteomics; D013997:Time Factors; D014184:Transplantation, Homologous
chemical_list: D006182:H-Y Antigen; C051256:H-Y antibody; D007518:Isoantibodies