title: Soluble interferon-gamma receptor and interferon-gamma in patients undergoing allogeneic bone marrow transplantation for hematological malignancies.
abstract: Interferon-gamma (IFN-gamma) is known to be involved in graft rejection of solid organs and acute graft-versus-host disease (GVHD). Its role, and especially that of soluble IFN-gamma receptor (sIFN-gamma R), in bone marrow transplantation (BMT) has not been established. We evaluated the sera of 27 patients following BMT. Fourteen of them underwent uneventful BMT, whereas 13 developed transplant-related complications, including acute GVHD (n = 5), early rejection (n = 4), or relapse of basic disease (n = 4). Soluble IFN-gamma R and IFN levels were evaluated at day -10 (preconditioning), day 0 (day of BMT), day of engraftment, and during BMT-related complications using sIFN-gamma R-specific monoclonal antibodies (McAB) followed by double-sandwich ELISA, and a sensitive radioimmunoassay respectively. In normal controls (n = 80) sIFN-gamma R and IFN-gamma levels in the sera were 0.5 +/- 0.05 and 0.3 +/- 0.04 ng/ml respectively. Soluble IFN-gamma R levels increased in direct correlation with engraftment (0.63 +/- 0.11 ng/ml at the day of BMT to 1.43 +/- 0.16 ng/ml at the day of engraftment; n = 14; P < 0.001). IFN-gamma levels increased in direct correlation with engraftment (0.37 +/- 0.03 ng/ml at the day of BMT to 5.69 +/- 1.64 ng/ml at the day of engraftment; n = 14; P < 0.001). In five patients with GVHD sIFN-gamma R levels increased from 0.43 +/- 0.19 ng/ml at the day of BMT to 1.73 +/- 0.17 ng/ml (P < 0.004) at the time of GVHD. Similarly, IFN-gamma levels increased from 0.43 +/- 0.08 ng/ml at the day of BMT to 3.03 +/- 0.5 ng/ml at the time of GVHD (P < 0.05). Both graft rejection and early relapse were associated with an elevation of IFN-gamma levels. In short, both s-IFN-gamma R and IFN-gamma were found to be significantly elevated during engraftment and GVHD. Hence these cytokines may be used as a tool for assessing engraftment and AGVHD.
authors.affiliation: Department of Bone Marrow Transplantation, Hadassah University Hospital, Jerusalem, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Toren
authors.forename: V
authors.initials: V
authors.lastname: Barak
authors.forename: D
authors.initials: D
authors.lastname: Novick
authors.forename: A
authors.initials: A
authors.lastname: Nagler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000097:blood*; D007938:Leukemia / Q000628:therapy*; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000628:therapy*; D011863:Radioimmunoassay; D017471:Receptors, Interferon / Q000097:blood*; D012995:Solubility; D014184:Transplantation, Homologous
chemical_list: D017471:Receptors, Interferon; D007371:Interferon-gamma