IN-UTERO TRANSPLANTATION OF PARENTAL CD34 HEMATOPOIETIC PROGENITOR CELLS IN A PATIENT WITH X-LINKED SEVERE COMBINED IMMUNODEFICIENCY (SCIDXI)

Background X-linked severe combined immunodeficiency (SCIDXI) is an in herited immune defect which leads to death in infancy from severe infe ctions. The defect is caused by mutations of the IL-2RG gene that enco des for the common gamma chain shared by several cytokine receptors. T he disease is characterised by lack of T and NK cells with normal numb ers of B cells. SCIDXI can be cured by bone marrow transplantation (BM T) or prevented by abortion after prenatal diagnosis. Methods A male f etus was diagnosed as having SCIDXI by molecular, immunophenotypic, an d functional analyses. The fetus was injected intraperitoneally under ultrasound guidance with CD34 haematopoietic progenitor cells purified from paternal bone marrow and T-cell depleted by E resetting. Chimeri sm analysis was by HLA-DQ alpha typing and gamma-chain staining on cor d blood. Findings A healthy 3.6 kg boy was delivered by caesarean sect ion at 38 weeks of gestation with no clinical or laboratory signs of g raft-versus-host disease. Engraftment of donor-derived CD2 cells was f ound at birth, At 3.5 months of age the infant is well and his T-cell counts and function are normal. Interpretation In-utero transplantatio n of haematopoietic progenitor cells allowed immune reconstitution of a fetus with SCIDXI and may be an alternative to elective abortion. Ou r report should encourage applications of this method to other inherit ed disorders curable by BMT.