title: Allogeneic bone marrow transplantation restores IGF-I production and linear growth in a gamma-SCID patient with abnormal growth hormone receptor signaling.
abstract: Severe combined immunodeficiency (SCID) is a heterogeneous group of disorders characterized by a severe defect of both T- and B-cell immunity, which generally require allogeneic bone marrow transplantation (BMT) within the first years of life. We previously reported a patient affected with an X-linked SCID due to L183S hemizygous missense gamma chain mutation, whose severe short stature was due to a peripheral growth hormone (GH) hyporesponsiveness associated to abnormal GH receptor (GH-R) signal transduction. In this study, we report the effect of BMT on the GH-R/insulin-like growth factor I (IGF-I) axis. After BMT, the patient showed a significant improvement in linear growth and normalization of basal- and GH-stimulated IGF-I values, which paralleled a fully competent immunological reconstitution. This suggests that cells derived from the hematopoietic stem cell may exert an unexpectedly significant role in producing IGF-I. This may also suggest that stem cell-based therapies may be useful for the correction of non-hematopoietic inherited disorders, such as those of GH-R/IGF-I axis.
authors.affiliation: Department of Pediatrics, Federico II University, Naples, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Salerno
authors.forename: R
authors.initials: R
authors.lastname: Busiello
authors.forename: V
authors.initials: V
authors.lastname: Esposito
authors.forename: E
authors.initials: E
authors.lastname: Cosentini
authors.forename: M
authors.initials: M
authors.lastname: Adriani
authors.forename: C
authors.initials: C
authors.lastname: Selleri
authors.forename: B
authors.initials: B
authors.lastname: Rotoli
authors.forename: C
authors.initials: C
authors.lastname: Pignata
mesh_terms: D016026:Bone Marrow Transplantation; D006085:Graft Survival; D006128:Growth; D006801:Humans; D007107:Immune System / Q000502:physiology; D007142:Immunoglobulin gamma-Chains / Q000235:genetics; D007223:Infant; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000172:deficiency; D008297:Male; D011986:Receptors, Somatotropin; D012038:Regeneration; D016511:Severe Combined Immunodeficiency / Q000628:therapy*; D015398:Signal Transduction; D014184:Transplantation, Homologous
chemical_list: D007142:Immunoglobulin gamma-Chains; D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I