Severe combined immunodeficiency patients: Immune recovery after stem cell transplantation

Abstract

Severe Combined Immunodeficiency (SCID) is a group of inherited disorders characterized by highly impaired cellular and humoral immunity, which causes an increased risk of persistent opportunistic infections that could be fatal, if untreated, at very early age. The treatment of choice is hematopoietic stem cell transplantation (HSCT) without conditioning from human leukocyte antigen-identical donor siblings; haploidentical parental donors are also successfully used. Several factors, including the type of SCID, transplantation in the neonatal period and lack or proper prevention of graft versus host disease, are associated with a better outcome after transplantation. Moreover, a rapid immune reconstitution is crucial for all patients undergone stem cell transplantation, but while T-cell reconstitution is observed during the first years after HSCT in most patients with SCID, correction of B-cell function is often more problematic. Generally, T-cell immunity recovers within about a year after HSCT, whereas B-cell immunity recovers more slowly. Measurement of T-cell receptor excision circles (TRECs) in peripheral blood is a mean of thymic T-cell production and it has been used in many studies to estimate thymus-dependent T-cell reconstitution after transplantation. We have recently proposed a new assay that, quantifying simultaneously TRECs and kappa-deleting recombination excision circles, measures the output of T and B cells from the thymus and bone marrow, and we have applied it to immune reconstitution analysis in patients with SCID.