B cell function after haploidentical in utero bone marrow transplantation in a patient with severe combined immunodeficiency.
An in utero paternal CD34(+) cell transplant was performed in a T-B+NK+ SCID fetus. We report here the results of the 3-year humoral immune reconstitution study. The methods used were ApoB VNTR typing, flow cytometry, nephelometry, hemagglutination, ELISA, ELISPOT and lymphoproliferative assays. The T cells were of donor origin whereas monocytes, B and NK cells were of host origin. Peripheral B cell counts and IgM levels were normal since birth. IVIG therapy was required at 5 months of age until 2 years old. IgA levels > or =20 mg/dl were detected from month 17 post transplantation. Isohemagglutinins were present since month 8 post transplantation, the highest titers (anti-A:1/128, anti-B:1/32) were obtained at month 33 post-transplantation. After immunization with rHBsAg, circulating anti-HBsAg IgG secreting cells and a 7.8-fold increase in serum anti-HBsAg Ab were detected. We conclude that split chimerism following in utero haploidentical BMT allows complete humoral immune reconstitution in a T-B+NK+ SCID patient.
Bartolomé
J
J
Division of Immunology, Hospital General Universitario 'Gregorio Marañón', Madrid, Spain.
Porta
F
F
Lafranchi
A
A
Rodríguez-Molina
J J
JJ
Cela
E
E
Cantalejo
A
A
Fernández-Cruz
E
E
Gómez-Pineda
A
A
Ugazio
A G
AG
Notarangelo
L D
LD
Gil
J
J
D000917:Antibody Formation; D001055:Apolipoproteins B / Q000235:genetics; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D015415:Biomarkers; D016026:Bone Marrow Transplantation / Q000379:methods*; D019070:Cell Lineage; D003241:Consanguinity; D005220:Fathers; D005315:Fetal Diseases / Q000175:diagnosis / Q000196:embryology / Q000235:genetics / Q000628:therapy*; D005500:Follow-Up Studies; D006085:Graft Survival; D006239:Haplotypes / Q000235:genetics; D006648:Histocompatibility; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis; D016130:Immunophenotyping; D007231:Infant, Newborn; D019520:Living Donors; D008297:Male; D018598:Minisatellite Repeats; D011296:Prenatal Diagnosis; D016511:Severe Combined Immunodeficiency / Q000175:diagnosis / Q000196:embryology / Q000235:genetics / Q000628:therapy*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D018183:Transplantation Chimera / Q000276:immunology*; D014611:Vaccination
D001055:Apolipoproteins B; D015415:Biomarkers; D007070:Immunoglobulin A