2013 Volume 23 Issue 2 Pages 41-49
Severe combined immunodeficiency (SCID) is a fatal syndrome of diverse genetic causes characterized by profound deficiencies of T cell and B cell function. In the absence of therapy, the lack of adaptive immunity results in overwhelming infections and death within the first year of life. Hematopoietic stem cell transplantation (HSCT) is a curative treatment for SCID. Although SCID patients are deficient in T cells, graft failure and prolonged mixed chimerism have occurred in some cases with SCID after HSCT. To explore the mechanisms that underlie these pathogenic conditions, we analyzed the chimerism of each leukocyte subset in two cases with SCID after HLA-mismatched cord blood transplantation (CBT) using flow cytometry, HLA-Flow. We found that the mixed chimerism in myeloid cells persisted for several years after CBT in both cases. In addition, the chimerism and the colony-forming ability were recipient dominant in the hematopoietic stem/progenitor cells (HSPC) of the patient two months after CBT. It showed that the replacement of recipient-derived HSPC by donor-derived ones had not been sufficient. The development of recipient-derived memory B cells in SCID patient with T−B＋NK− phenotype was skewed compared with donor-derived ones. These data suggest that the necessity of long-term support of intravenous immunoglobulin in SCID after HSCT is concerned with the insufficient replacement of HSC. HLA-Flow was very useful to investigate the pathophysiology of the immunological disorders after HSCT in SCID.
