Biomedical subjects

Claudio Gasperini

Publications and source records attributed to Claudio Gasperini.

3 recordsLinked to original sources

PubMed2003

CD8+ T cells from patients with acute multiple sclerosis display selective increase of adhesiveness in brain venules: a critical role for P-selectin glycoprotein ligand-1.

Multiple sclerosis (MS) is considered an autoimmune inflammatory disease of the central nervous system. Under physiologic conditions, we compared the adhesiveness of CD4+ and CD8+ lymphocytes from nontreated patients with acute, relapsing-remitting multiple sclerosis (RRMS) and from healthy donors. We show that in patients with RRMS CD8+, but not with RRMS CD4+, T cells display increased rolling and arrest in inflamed murine brain venules. Moreover, CD8+, but not CD4+, lymphocytes from MS patients show increased rolling on P-selectin in vitro. Anti-P-selectin glycoprotein ligand-1 (PSGL-1) antibodies dramatically block the recruitment of CD8+ cells in brain vessels of patients with MS, suggesting that PSGL-1 represents a novel pharmaceutical target that may be exploited to block the selective entrance of CD8+ cells during early inflammation. Vascular cell adhesion molecule-1 (VCAM-1), but not PSGL-1, is critical for the adhesion of CD4+ cells in MS patients, highlighting a fundamental dichotomy in the mechanisms governing the recruitment of lymphocyte subsets in RRMS. Importantly, 7-color fluorescence-activated cell sorter (FACS) analysis, together with functional data, indicates that a large fraction of CD8+ cells from MS patients display the characteristics of memory-effector phenotype. In conclusion, our results show that CD8+, but not CD4+, T cells from patients with RRMS in the acute phase of the disease display increased ability to be recruited in inflamed brain venules.

Acute Disease↗

PubMed2002

Monthly corticosteroids decrease neutralizing antibodies to IFNbeta1 b: a randomized trial in multiple sclerosis.

Neutralizing antibodies (NAB) to interferon beta (IFNbeta) occur in some multiple sclerosis (MS) patients, particularly during the first year of treatment. The presence of NAB may be associated with an attenuation of the therapeutic effect. The aim of this study was to compare the frequency of NAB occurrence in patients treated with IFNbeta-1 b with that in patients treated with IFNbeta-1 b combined with monthly pulses of intravenous methylprednisolone (MP). One hundred and sixty-one patients with relapsing-remitting MS were randomized in two treatment arms: 8 MIU of IFNbeta- 1 b subcutaneously injected every other day either alone or in combination with 1000 mg of monthly intravenous MP. NAB were evaluated at baseline and at months 3,6,9,12 and 15 by the MxA assay in a specialized laboratory. Positivity was defined as a titer of > or = 20 neutralizing units according to two different definitions: I) one or more non-consecutive positive samples, II) at least two consecutive positive samples. NAB (definition I) were observed in 26.8% of patients in the IFNbeta-1 b alone arm and in 12.1% of patients in the combination therapy arm (p = 0.05 by the chi-square test), which corresponds to a relative reduction of 54.9%, whereas according to definition II, these figures dropped to 22.5 % for the IFNbeta-1 b alone arm, and 10.6% for the combination therapy arm (relative reduction 52.9%, p = 0.10, NS). A higher probability of remaining in the NAB-free status was observed in patients treated with the combination therapy (p = 0.031 for definition I and p = 0.o49 for definition II, by the Wilcoxon-Gehan test). Methylprednisilone combined with IFNbeta-1 b reduces the incidence of neutralizing bodies to in terferon-beta during the first year of treatment in MS patients.

Adjuvants, Immunologic↗

PubMed2002

Proteolytic balance in patients with multiple sclerosis during interferon treatment.

Multiple sclerosis (MS) is a progressive, inflammatory, demyelinating disease. An altered cytokine network has been reported to occur during the disease, and its pathogenetic role has been hypothesized. To date, interferon-beta (IFN-beta) is the most effective and reliable therapy in the majority of MS patients, although the mechanisms underlying its therapeutic effects are not fully understood. Breakdown of the blood-brain barrier (BBB) with consequent extravasation of the T cells and their invasion of the brain parenchyma seems to be one of the most important steps in the pathogenesis of the disease. Matrix metalloproteinease-2 (MMP-2) and MMP-9 are enzymes with proteolytic activities toward extracellular matrix ECM components. They are physiologically balanced by the MMP tissue inhibitors TIMP-2 and TIMP-1, so that proteolysis occurs as the result of increased MMP or decreased TIMP levels. In 38 patients with MS, MMP-2 and TIMP-1 levels were similar before and after 9 months of IFN-beta therapy, whereas MMP-9 levels significantly decreased and TIMP-2 levels significantly increased in comparison to values obtained before treatment. These results suggest that IFN-beta modulates T cell activities, including MMP and TIMP production, thus contributing either to maintaining the integrity of the BBB or to slowing the progression of the disease.

Adolescent↗