Showing papers by "Luisa Imberti published in 2012"

Pre-Existing T- and B-Cell Defects in One Progressive Multifocal Leukoencephalopathy Patient

Abstract: Progressive multifocal leukoencephalopathy (PML) usually occurs in patients with severe immunosuppression, hematological malignancies, chronic inflammatory conditions or receiving organ transplant. Recently, PML has also been observed in patients treated with monoclonal antibodies. By taking advantage of the availability of samples from a multiple sclerosis (MS) patient treated with natalizumab, the antibody anti-α4 integrin, who developed PML and was monitored starting before therapy initiation, we investigated the fate of T and B lymphocytes in the onset of PML. Real-time PCR was used to measure new T- and B-cell production by means of T-cell receptor excision circle (TREC) and K-deleting recombination excision circle (KREC) analysis and to quantify transcripts for CD34, terminal-deoxynucleotidyltransferase, and V pre-B lymphocyte gene 1. T- and B-cell subsets and T-cell heterogeneity were measured by flow cytometry and spectratyping. The data were compared to those of untreated and natalizumab-treated MS patients and healthy donors. Before therapy, a patient who developed PML had a low TREC and KREC number; TRECs remained low, while KRECs and pre-B lymphocyte gene 1 transcripts peaked at 6 months of therapy and then decreased at PML diagnosis. Flow cytometry confirmed the deficient number of newly produced T lymphocytes, counterbalanced by an increase in TEMRA cells. The percentage of naive B cells increased by approximately 70% after 6 months of therapy, but B lymphocyte number remained low for the entire treatment period. T-cell heterogeneity and immunoglobulins were reduced. Although performed in a single patient, all results showed that an immune deficit, together with an increase in newly produced B cells a few months after therapy initiation, may predispose the patient to PML. These findings indicate the TREC/KREC assay is a potential tool to identify patients at risk of developing PML and may provide insights into the immunological involvement of monoclonal antibody-associated therapies.

Modulation of the central memory and Tr1-like regulatory T cells in multiple sclerosis patients responsive to interferon beta therapy

Abstract: Background: Interferon-beta is used to reduce disease activity in multiple sclerosis, but its action is incompletely understood, individual treatment response varies among patients, and biological markers predicting clinical benefits have yet to be identified. Since it is known that multiple sclerosis patients have a deficit of the regulatory T-cell subsets, we investigated whether interferon-beta therapy induced modifications of the two main categories of regulatory T cells (Tregs), natural and IL-10-secreting inducible Tr1 subset, in patients who are biologically responsive to the therapy.Methods: T-cell phenotype was determined by flow cytometry, while real-time PCR was used to evaluate interferon-beta bioactivity through MxA determination, and to measure the RNA for IL-10 and CD46 molecule in peripheral blood mononuclear cells stimulated with anti-CD46 and anti-CD3 monoclonal antibodies, which are known to expand a Tr1-like population.Results: Interferon-beta induced a redistribution of natural Treg s...

Effects of combined antiretroviral therapy on B- and T-cell release from production sites in long-term treated HIV-1+ patients

Abstract: Background The immune system reconstitution in HIV-1- infected patients undergoing combined antiretroviral therapy is routinely evaluated by T-cell phenotyping, even though the infection also impairs the B-cell mediated immunity. To find new laboratory markers of therapy effectiveness, both B- and T- immune recovery were evaluated by means of a follow-up study of long-term treated HIV-1- infected patients, with a special focus on the measure of new B- and T-lymphocyte production.

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.