Showing papers by "Luisa Imberti published in 2005"
TL;DR: Data indicate that decreased thymic function, B cell oligoclonality, and increased spontaneous apoptosis may be the mechanisms by which the immunodeficiency of ADA‐SCID patients persists in spite of treatment with PEG‐ADA.
Abstract: Impairment of purine metabolism due to adenosine deaminase (ADA) deficiency is associated with a severe combined immunodeficiency (SCID). Polyethylene glycol-modified ADA (PEG-ADA) has provided noncurative, life-saving treatment for these patients, but full immune recovery is not achieved with this therapy. Since ADA-SCID is perhaps the most difficult form of SCID to handle clinically, understanding the benefits and limitations of PEG-ADA therapy may be relevant for treatment selection. To this purpose, we analyzed the rate of thymic output, T and B cell repertoires, number of T cell divisions, IFN-gamma and IL-4 production, and the extent of cell death in five ADA-SCID patients following a prolonged period of treatment with PEG-ADA. We found that thymic output was low in these patients. However, their T cell repertoire was heterogeneous, and their T lymphocytes produced cytokines upon activation and responded to mitogen stimulation, although with different kinetics. Furthermore, a high number of peripheral T lymphocytes were committed to apoptosis. Anomalies were also observed in the B cell compartment, with oligoclonal expansions of B cell clonotypes in two patients. Our data indicate that decreased thymic function, B cell oligoclonality, and increased spontaneous apoptosis may be the mechanisms by which the immunodeficiency of ADA-SCID patients persists in spite of treatment with PEG-ADA.
62 citations
TL;DR: Early recognition of OS, rapid initiation of adequate supportive treatment and HSCT lead to improved outcome for this otherwise fatal disease, regardless of the origin and matching of hematopoietic stem cells.
Abstract: We retrospectively analyzed the outcome of hematopoietic stem cell transplantations (HSCT) performed at our Center between 1991 and 2002 in 11 unselected patients with Omenn syndrome, a variant of severe combined immunodeficiency. The patients' mean age at the time of the first HSCT was 8.4 months. Two patients received two, and one patient three, HSCT procedures. The resulting 15 HSCT derived in seven cases from HLA-haploidentical parents, in four patients from matched unrelated donors, in three cases from an HLA phenotypically identical related donor, and in one case from an HLA genotypically identical family donor. Nine out of 11 patients are alive and immunoreconstituted 30-146 months after transplantation. At the time of the most recent evaluation, all of the nine survivors had normal T-cell function, and eight of them had developed normal antibody production. This study demonstrates an overall mortality of 18.2%, which is substantially lower than previously reported. Early recognition of OS, rapid initiation of adequate supportive treatment and HSCT lead to improved outcome for this otherwise fatal disease, regardless of the origin and matching of hematopoietic stem cells.
40 citations
TL;DR: The thymus of transplanted patients can be capable of generating new T cells, but there is no relationship between increasing number of newly produced lymphocytes and modification of IL-7 level, and high-dose therapy and HSCT might support the improvement of immune conditions.
Abstract: Background. One of the major concern for high-dose chemotherapy and hematopoietic stem cell transplantation (HSCT) for HIV-associated lymphoma is that posttransplant immunosuppression might worsen immune defects of HIV+ individuals. Since the introduction of highly active antiretroviral therapy has made HSCT possible also in these patients, we analyzed whether the immune system already compromised by HIV infection might support an efficient T-cell recovery after HSCT. Methods. The kinetics and the extent of T-cell reconstitution were investigated before and after HSCT in four patients with HIV-related lymphoma (one with Hodgkin's Disease and three with non-Hodgkin's lymphoma) by measuring the thymic output, the level of IL-7 and the heterogeneity of T-cell repertoire. T-cell competence was gauged at two functional levels: by determining the number of T-cell divisions and by measuring IFN-γ production. Results. The thymus of transplanted patients can be capable of generating new T cells, but there is no relationship between increasing number of newly produced lymphocytes and modification of IL-7 level. Various T-cell subsets, expressing different T-cell receptor variable beta genes, were preferentially expanded in CD8 population and most of them showed a restricted diversity. Furthermore, CD3+ lymphocytes showed heterogeneous behaviors in terms of proliferative capability and IFN-γ production. Conclusions. High-dose therapy and HSCT in HIV+ patients under highly active antiretroviral therapy does not worsen the immune defects. On the contrary, in the presence of some conditions (including the type of hematologic malignancy, the therapy compliance, and the immune status before transplantation), high-dose therapy and HSCT might support the improvement of immune conditions.
30 citations
TL;DR: The results indicate that patients who undergo hemodialysis can be at high risk of SENV transmission and suggest an intraunit transmission of specific SENV variants.
Abstract: Objective: The SEN virus (SENV) represents a recently described group of DNA viruses, two members of which (SENV-D and SENV-H) are linked with posttransfusion hepatitis. Since patients on hemodialysis have a high risk of being infected by blood-borne viruses, we investigated the prevalence of seven SENV isolates in two distinct units of our hospital. Methods: The presence of SENV was investigated in 171 hemodialysis patients and in 163 controls by using a polymerase chain reaction based methodology, with which the specificity of amplified products was detected by hybridization with probes specific for each variant. Polymerase chain reaction products from 4 patients were sequenced. Results: The overall detection of SENV DNA as well as of SENV-D, SENV-E, and SENV-G was significantly higher in one of the two units, and there was a higher degree of homology in the sequences prepared from patients of the same unit. Furthermore, we demonstrated that mixed infections with multiple SENV were common. No relationship was observed between presence of SENV and sex, age, duration of hemodialysis, previous transfusions or transplantation, hepatitis infection, and routine liver test results. Conclusion: Our results indicate that patients who undergo hemodialysis can be at high risk of SENV transmission and suggest an intraunit transmission of specific SENV variants.
5 citations