![]() Conflicting data exist on the relative contribution of ADA metabolites in the pathogenesis of the immune dysfunctions observed in ADA-deficient patients, but the biochemical hallmarks of this deficiency indicate that dAdo accumulation in intracellular and extracellular compartments is the primary cause of lymphotoxicity. The mobilization of TCR excision circle + cells, though lower than in controls, was stable with time after HSCT treatment, leading to a constant peripheral T cell number and to the diversification of the T cell repertoire however, it was compromised in children receiving prolonged PEG-ADA therapy, whose T cells showed progressively narrowing T cell repertoires.ĪDA is a purine salvage enzyme expressed in all tissues that is capable of catalyzing the deamination of deoxyadenosine (dAdo) and adenosine to deoxyinosine and inosine, respectively ( 4). ![]() The stable production of κ-deleting recombination excision circle + lymphocytes sustained an increase in B cell number in HSCT-treated patients, whereas in PEG-ADA–treated patients, it was accompanied by a significant and progressive decrease in circulating CD19 + lymphocytes, which never reached the levels observed in age-matched children. We found that immune reconstitution was different following the two treatments. Together with classical immunological parameters, we quantified the output of the new B and T cells from the production sites using the κ-deleting recombination excision circle and TCR excision circle assay, and we monitored T cell repertoire diversification. Because hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy with pegylated bovine ADA (PEG-ADA) are both provided in our hospital, we undertook a retrospective longitudinal comparative study of the extent of lymphocyte recovery in two groups of treated ADA-SCID children. If the disease is left untreated, it is likely to have a fatal outcome in early infancy. The lack of adenosine deaminase (ADA) leads to the accumulation of toxic metabolites, resulting in SCID.
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