Successful treatment with an unrelated-donor bone marrow transplant in an HLA-deficient patient with severe combined immune deficiency ("bare lymphocyte syndrome").

An 8-month-old white female infant with Pneumocystis carinii pneumonia had a normal blastogenic response to mitogens but no response to a variety of antigens, as well as a poor response to allogeneic cells in one-way mixed lymphocyte culture assays. The patient's mononuclear cells had defective class I (HLA-A, -B, -C) and absent class II (HLA-D) antigen expression on their surface, thus establishing the diagnosis of HLA-deficient severe combined immune deficiency (bare lymphocyte syndrome). Family HLA typing, in vitro stimulation of patient mononuclear cells, and sequence-specific oligonucleotide probe hybridization allowed the patients HLA phenotype to be determined. An unrelated bone marrow donor whose phenotype matched at all but a single A locus was found. The patient was conditioned with busulfan and cyclophosphamide, followed by infusion of T-cell-depleted bone marrow cells. The patient has been infection free with a successful marrow graft documented by HLA typing and chromosomal analysis. Sequence-specific oligonucleotide probe hybridization allows determination of the HLA phenotype in patients with HLA-deficient severe combined immune deficiency which, in turn, makes marrow transplantation an option for the reconstitution of these patients' immune system.