title: Persistent Mycobacterium avium infection following nonmyeloablative allogeneic peripheral blood stem cell transplantation for interferon-gamma receptor-1 deficiency.
abstract: Interferon-gamma receptor-1 (IFNgammaR1) deficiency is a rare inherited immunodeficiency. We performed a nonmyeloablative allogeneic stem cell transplantation on a boy with complete IFNgammaR1 deficiency and refractory disseminated Myco- bacterium avium infection. Despite the patient's profound immune defect, early donor stem cell engraftment was low. Full donor engraftment was accomplished only following multiple donor lymphocyte infusions. Detection of IFNgammaR1 expression on peripheral blood monocytes and neutrophils corresponded with establishment of stable, complete donor hematopoietic chimerism. However, expression of, and signaling through IFNgammaR1 disappeared shortly thereafter. Disseminated Mycobacterium avium infection persisted and the patient died. Coculture of Myco- bacterium avium with normal myeloid cells resulted in an IFNgamma signaling defect similar to that observed in vivo. Active disseminated Mycobacterium avium infection may significantly compromise normal immune reconstitution following allogeneic stem cell transplantation. Patients with IFNgammaR1 deficiency should receive transplants before developing refractory mycobacterial infections.
authors.affiliation: National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA. mitchell.horwitz@duke.edu
authors.forename: Mitchell E
authors.initials: ME
authors.lastname: Horwitz
authors.forename: Gulbu
authors.initials: G
authors.lastname: Uzel
authors.forename: Gilda F
authors.initials: GF
authors.lastname: Linton
authors.forename: Judi A
authors.initials: JA
authors.lastname: Miller
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Brown
authors.forename: Harry L
authors.initials: HL
authors.lastname: Malech
authors.forename: Steven M
authors.initials: SM
authors.lastname: Holland
mesh_terms: D002675:Child, Preschool; D006801:Humans; D016867:Immunocompromised Host; D008297:Male; D009000:Monocytes / Q000276:immunology; D015269:Mycobacterium avium Complex; D015270:Mycobacterium avium-intracellulare Infection / Q000150:complications* / Q000276:immunology*; D017471:Receptors, Interferon / Q000172:deficiency* / Q000235:genetics; D015398:Signal Transduction; D033581:Stem Cell Transplantation; D000096743:Interferon gamma Receptor
chemical_list: D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor