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1.
Biol Blood Marrow Transplant ; 5(1): 46-50, 1999.
Article in English | MEDLINE | ID: mdl-10232740

ABSTRACT

The long-term recipients of allogeneic bone marrow transplantation (BMT) are at an increased risk of death due to bacterial infections. We evaluated the anticarbohydrate antibody responses of BMT recipients to a naturally occurring bacterial carbohydrate, polyribose phosphate (PRP). The recipients of autologous BMT achieved protective anti-PRP levels (>100 ng/mL) by 3 years after transplantation, with a pattern consistent with a recapitulation of the ontogeny of anticarbohydrate antibody responses. None of the six recipients of unrelated BMT who were off immunosuppressive therapy had protective anti-PRP levels, though their response to a protein antigen (tetanus toxoid) was normal. Of 48 recipients of histocompatible BMT, 22 (46%) had protective anti-PRP antibody levels, whereas 13 (27%) recipients who were >3 years post-BMT did not have protective levels. Therefore, all unrelated recipients and a significant proportion of histocompatible recipients without clinical graft-vs.-host disease had persistent and prolonged defects in their capacity to produce antibodies to naturally occurring bacterial carbohydrate antigens. These results suggest that allogeneic BMT recipients should be longitudinally evaluated for their anticarbohydrate antibody responses and that patients with defective antibody responses should receive prophylactic antibiotics or replacement immunoglobulin therapy or both to reduce their risk of late bacterial infections.


Subject(s)
Bacterial Infections/immunology , Bone Marrow Transplantation/immunology , Opportunistic Infections/immunology , Pentosephosphates/immunology , Polysaccharides, Bacterial/immunology , Adolescent , Adult , Antibody Formation , Child , Child, Preschool , Histocompatibility Testing , Humans , Infant , Infant, Newborn , Linear Models , Transplantation, Autologous , Transplantation, Homologous
2.
Nat Med ; 4(7): 775-80, 1998 Jul.
Article in English | MEDLINE | ID: mdl-9662367

ABSTRACT

Adenosine deaminase-deficient severe combined immunodeficiency was the first disease investigated for gene therapy because of a postulated production or survival advantage for gene-corrected T lymphocytes, which may overcome inefficient gene transfer. Four years after three newborns with this disease were given infusions of transduced autologous umbilical cord blood CD34+ cells, the frequency of gene-containing T lymphocytes has risen to 1-10%, whereas the frequencies of other hematopoietic and lymphoid cells containing the gene remain at 0.01-0.1%. Cessation of polyethylene glycol-conjugated adenosine deaminase enzyme replacement in one subject led to a decline in immune function, despite the persistence of gene-containing T lymphocytes. Thus, despite the long-term engraftment of transduced stem cells and selective accumulation of gene-containing T lymphocytes, improved gene transfer and expression will be needed to attain a therapeutic effect.


Subject(s)
Adenosine Deaminase/immunology , Antigens, CD34/immunology , Hematopoietic Stem Cell Transplantation , T-Lymphocytes/immunology , Transplantation Immunology/immunology , Adenosine Deaminase/deficiency , Adenosine Deaminase/genetics , Adenosine Deaminase/metabolism , Animals , Animals, Newborn , Cell Line , Flow Cytometry , Gene Frequency , Granulocytes/immunology , Humans , Leukocytes, Mononuclear/immunology , Lymphocyte Count , Mice , Mice, SCID , Polyethylene Glycols , T-Lymphocytes/drug effects , Transformation, Genetic , Transplantation, Autologous , Umbilical Cord
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