To analyze immunohematologic reconstitution, particularly of natural killer (NK) cells, we evaluated 13 β-thalassemia patients after 20 and 60 days and 1 year posttransplantation with T cell-depleted HLA-haploidentical stem cells. We assessed lymphocyte and bone marrow (BM) progenitor cell phenotype and differentiation capacity, spontaneous BM cytokine production, stromal cells, and stromal cell interleukin (IL)-7 production. A reduced clonogenic capability manifested at day +20.
View Article and Find Full Text PDFTreatment of multi-drug experienced patients is an important concern in the management of HIV-1 disease, partially solved by the availability of new drugs acting at different phases of viral replication. Immune recovery during cART is linked both to the activity of antiviral drugs, as well as to the regenerative capability of thymus and bone marrow. We report a patient with a 22-year-old HIV-1 disease and an AIDS diagnosis for 15 years, with extensive resistance to all antiretroviral drugs, who never had treatment interruption, except for short spells due to adverse effects.
View Article and Find Full Text PDFBackground: Inflammatory cytokines in bone marrow may impair hematolymphopoiesis in human immunodeficiency virus (HIV)-infected subjects who do not experience reconstitution of CD4(+) T cells despite suppression of virus replication while receiving highly active antiretroviral therapy (HAART) (immunological nonresponders).
Methods: Bone marrow samples from 12 immunological nonresponders receiving HAART were studied and compared with samples from 11 immunological responders. The mean CD4(+) T cell count (+/- standard deviation) was 174 +/- 68 cells/mm(3) and plasma HIV RNA levels had been <50 copies/mL for at least 1 year for individuals enrolled in the study.
Background: Evans syndrome (ES) is a rare disorder characterized by combined autoimmune thrombocytopenia and autoimmune hemolytic anemia. Several studies have documented a number of B cell defects, whereas only limited information is currently available about the T cell subset.
Methods: A wide panel of immunological analyses aiming specifically at a quantitative and qualitative evaluation of the T cell compartment was performed in an unusual case of ES.
Hematopoiesis in the bone marrow (BM) is maintained by specific interactions between both hematopoietic and non-hematopoietic stromal cells, which are mesenchymal stem cells (MSCs) capable of giving rise to several cell types. The human periodontal ligament (PDL), a tissue of ectomesenchymal origin, has been shown to also be a source of MSCs. We have investigated whether MSCs expanded from the PDL of healthy volunteers express characteristics similar to BM-derived stem cells using structural, immunocytochemical and molecular approaches.
View Article and Find Full Text PDFWe report the results of an external quality control program, including 17 Italian centers involved in the care of patients infected by HIV, to evaluate CD4 T cell count proficiency and reproducibility. The centers received two commercial stabilized blood preparations, one with "normal" and one with "low" CD4 T cell content. The centers were asked to process the samples two times, 1 week apart, with the same procedure used for samples from HIV patients.
View Article and Find Full Text PDFWe investigated several phenotypic and functional parameters of T cell-mediated immunity in a large series of common variable immunodeficiency (CVID) patients. We demonstrated that the vast majority of CVID patients presented multiple T cell abnormalities intimately related among them, the severity of which was reflected in a parallel loss of CD4+ naive T cells. A strong correlation between the number of CD4+ naive T cells and clinical features was observed, supporting the subgrouping of patients according to their number of naive CD4+ T lymphocytes.
View Article and Find Full Text PDFObjective: To investigate the pathogenesis of low CD4 T-cell count in subjects who are immunological non responders (InR) to HAART.
Design: Thirty-five HIV-positive subjects on HAART for at least 1 year, all with undetectable HIV-1 RNA, were studied. Patients were defined as InR according to a CD4 cell increase < 20% from CD4 cell baseline or CD4 cell count < 200/microl; subjects with a CD4 T-cell increase > 20% from baseline and a CD4 cell count > 200/microl were defined as immunological responders (IR).
HAART in HIV-1-infected individuals has a broad spectrum of clinical outcomes. In the majority of patients, plasma viral load becomes undetectable and CD4+ T-cells increase over time. However, in a number of subjects a discrepancy between plasma viral load and the CD4+ T-cell recovery is observed.
View Article and Find Full Text PDFThe case of a 20-year-old patient, affected by X-linked agammaglobulinaemia (XLA), who developed severe pneumonia from Pneumocystis jiroveci (formerly Pneumocystis carinii) (PCP), is reported. This infection usually affects patients with AIDS, children affected by severe combined immunodeficiency or hypogammaglobulinaemia with hyperimmunoglobulin M, or patients undergoing severe immunosuppression. The XLA patient developed PCP during therapy with steroids and cyclosporine A, carried out for several months, due to an extended skin vasculitis, accompanied by general symptoms.
View Article and Find Full Text PDFHematological abnormalities frequently occur in patients infected with HIV-1. Increasing evidence indicates that bone marrow (BM) suppression results from viral infection of accessory cells, with impaired stromal function and alteration of hematopoietic growth factor network. We investigated the effects of antiretroviral therapy on cytokine and chemokine production by BM cells and stromal cells, in a group of HIV-1-infected subjects before and during treatment.
View Article and Find Full Text PDFIn patients with primary Ab deficiencies, hematological and immunological abnormalities are frequently observed. A regenerative failure of hemopoietic stem/progenitor cells has been hypothesized. We evaluated in the bone marrow (BM) of 11 patients with common variable immunodeficiency, the phenotype of BM progenitors and their in vitro growth by colony-forming cell (CFC) and long-term culture (LTC) assays.
View Article and Find Full Text PDFBackground: Idiopathic CD4+ lymphocytopenia is defined by a stable decrease of CD4+ T cells in the absence of any known cause of immune deficiency. The mechanisms responsible for the immunological impairment are still unknown, but a regenerative failure of hematopoietic stem/progenitor cells has been hypothesized.
Methods: We evaluated in the bone marrow (BM) of 5 patients with idiopathic CD4+ lymphocytopenia the phenotype of BM progenitor cells, their differentiation capacity with colony-forming cells and long-term culture-initiating cell assays, in parallel with the spontaneous IL-7 production in the patient sera.
Background: Recurrent lower respiratory tract infections caused by encapsulated bacteria might cause permanent organ damage in patients with common variable immunodeficiency (CVID). Despite the profound hypogammaglobulinemia, some patients do not experience bacterial pneumonia. We have shown that IgM memory B cells and natural antibodies play an important role in the defense against encapsulated bacteria.
View Article and Find Full Text PDFHIV-1 protease inhibitors (PIs) may improve hematopoietic functions owing to their direct effects on bone marrow (BM) progenitor cells. In this study we investigated this hypothesis evaluating the effect of adding ritonavir (RTV) and indinavir (IND) on hematopoietic colony formation assays by colony-forming cell (CFC) and long-term culture-initiating cell (LTC-IC) assays, on apoptosis, on cytokine production and stromal cells, in subjects with HIV-1 infection, and in seronegative controls. After PI addition, CFC and LTC-IC assays in HIV-1-infected patients showed levels of colony growth significantly higher than those observed at baseline; the same PI activity on colony formation was observed in healthy subjects.
View Article and Find Full Text PDFImpaired haematopoiesis during HIV-1 infection may be caused by the overproduction of inflammatory cytokines by immune cells at the bone marrow level inducing Fas-mediated apoptosis of stem progenitors. In this study, we evaluated the effects of highly active antiretroviral therapy on apoptosis of CD34+ stem cells derived from the bone marrow of HIV-1-infected patients, and observed decreased Fas expression on progenitor cells, in parallel with the diminution of TNF-alpha levels and the amelioration of clonogenic parameters.
View Article and Find Full Text PDFJ Acquir Immune Defic Syndr
October 2003
In most HIV-1-infected patients, highly active antiretroviral therapy (HAART) reduces plasma viral load to <50 copies/mL and increases CD4+ T-cell number and function. However, it is still unclear whether alterations of T-cell receptor (TCR) beta-chain variable region (BV) repertoire, tightly related to disease progression, can be fully recovered by long-term treatment with HAART. This study analyzed the evolution of both T-cell subset composition and TCRBV perturbations in chronically HIV-1-infected patients with moderate immunodeficiency during 36 months of HAART.
View Article and Find Full Text PDFThe aim of this work was a review of literature with regard to the mucosal immunity, the oral vaccines and the bacterial lysates. The Gut Associated Lymphoid Tissue (GALT) include effector and inductive sites and is constituted by organized and diffuse tissues. GALT defends the integrity of the gut, inhibits the development of allergy and autoimmunity and induce a mucosal and systemic immune response against enteric antigens.
View Article and Find Full Text PDFObjectives: Common variable immunodeficiency (CVID) is an immunological disorder characterized by defective antibody production. An increased prevalence of celiac disease has been suggested in patients with this disorder. This study aimed to assess duodenal pathology and its clinical implications in these patients.
View Article and Find Full Text PDFA European multicenter study was conducted to obtain information on the current practices of immunoglobulin administration, the policies in use for the surveillance of the risk of hepatitis C virus (HCV) transmission, and the natural history of HCV infection in patients with hypogammaglobulinemia. Data from 1243 patients with primary immunodeficiencies in 16 countries demonstrated that 90% of patients with antibody deficiencies receive intravenous immunoglobulins in an inpatient setting, and 7% of patients are treated with subcutaneous immunoglobulins, mainly at home. Wide variations have been reported regarding the frequency and the type of tests monitored for the surveillance on the risk of viral hepatitis transmission.
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