3). Moreover, the CD4+ T cells were mostly CD45RO+ and remained as such for up to 7 months after ERT. Nevertheless, after 17 months all his CD4+ and CD8+ T cells became CD45RA+ [13]. Therefore, it is possible HSP inhibitor that differences in the revertant phenotypes attributed to long-term exposure to ADA in the context of the deficiency might reflect differences in how the T cells are reconstituted with PEG-ADA. In addition, differences in PEG-ADA administration dosages and regularity as well as different residual thymic function at the time of initiation of the ERT could have also contributed to these differences among patients. In fact, while in the patient reported by Liu et al. the CD4, CD8 and B cells

steadily increased, in our patient those numbers returned to pre-PEG-ADA levels after the initial expansion. Therefore, it is also possible that the high level of CD45RO+ CD4+ and CD8+ T cells that were observed during the first months of ERT in our patient resulted from the expansion of CD3+ TCRαβ+ T cells. On the other hand, the total numbers of CD19+ B cells MG-132 cell line in our patient remained well below the normal throughout the ERT. This contrasts with findings by others showing that B cells from ADA-deficient patients with or without revertant

T cells reach steady numbers during the first months of treatment [13, 28]; the reason for this variability among patients remains unclear. In addition, recovery of function of B cells in response to immunization after ERT have yielded variable results with absent or [13] or normal humoral responses [29]. Unfortunately, we were unable to evaluate them in our patient. Liu et al. [13] reported that the initial TCRvβ repertoire in the T cells from their patient was substantially restricted and consistent with a dominant oligoclonal CD8+ population; however, after 8 months, it became more polyclonal and correlated with the accumulation

of naïve T cells in response to ERT. We only analysed the TCRvβ repertoire in our patient after 12 months of ERT, and the results showed that it was markedly oligoclonal (Fig. 4). We did not look for naïve T cells at this time nor we performed additional spectratyping later; nevertheless, this could be partly explained by the preferential expansion of TCRγδ+ T cells observed early during ETR, Bcl-w as these cells are known to have a restricted TCR repertoire. It has also been reported that PEG-ADA therapy normalizes toxic levels of Ado and dAdo, allowing the ADA-deficient cells to survive, while the revertant cells lose their selective advantage [11, 12]. Our results also showed that the signal of revertant cells disappeared gradually and was no longer detectable after 6 months of PEG-ADA therapy, (Fig. 5). Therefore, the marginal immune function observed in our patient is probably a reflection of the selective advantage conferred to the newly formed cells by the PEG-ADA therapy.