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C Buttinelli

Publications and source records attributed to C Buttinelli.

At least 37 records · Page 2Linked to original sources
PubMed1996

The immune response to mycobacterial 70-kDa heat shock proteins frequently involves autoreactive T cells and is quantitatively disregulated in multiple sclerosis.

Heat shock proteins (HSP) are the most conserved molecules known to date that may also function as immune targets during infection. Hence, theoretically there is a high chance of cross-reactive responses to epitopes shared by host and microbe HSP. If not properly regulated, these responses may contribute to the pathogenesis of autoimmune disease. To determine if immune responses to HSP could contribute to the pathogenesis of multiple sclerosis, we raised T lymphocyte lines specific for the purified protein derivative of Mycobacterium tuberculosis (PPD) from patients with multiple sclerosis, patients with tuberculosis and from healthy individuals. These lines were then screened for their proliferative response to a M. tuberculosis 70-kDa heat shock protein (M.tb.HSP70). The relative frequency of the recognition of highly conserved sequences of M.tb.HSP70 compared to variable ones was also assessed by mapping experiments on those PPD specific T lymphocyte lines which also recognized the mycobacterial 70-kDa heat shock protein. In patients with multiple sclerosis, we observed a significantly higher estimated frequency of PPD-specific T lines responding to M.tb.HSP70 compared to healthy individuals and patients with tuberculosis. Furthermore, mapping experiments using recombinant proteins representing mycobacterial and human HSP70 sequences and a panel of synthetic peptides encompassing the whole sequence of Mycobacterium leprae HSP70, showed that the response to conserved epitopes of HSP70 is a frequent event in each of the three conditions studied, often leading to the cross-recognition of microbial and human sequences. These findings implicate the 70-kDa heat shock proteins as potential autoantigens in multiple sclerosis.

Adult↗
PubMed1996

Magnetic resonance imaging changes with recombinant human interferon-beta-1a: a short term study in relapsing-remitting multiple sclerosis.

OBJECTIVE: To evaluate whether recombinant human interferon-beta-1a significantly affects disease activity as measured by a reduction in the number and volume of Gd enhancing lesions on monthly MRI. The study also evaluated the effect on six-monthly T2 weighted abnormality and relapse frequency. METHODS: After a baseline scan and a six month pretreatment period, 68 patients were randomly assigned to receive either 3 MIU or 9 MIU of interferon-beta-1a by subcutaneous injection three times a week for six months. All patients were examined by Gd enhanced MRI every month in both pretreatment and treatment periods. The evaluation of Gd enhancing lesions was performed blind at the end of the study. RESULTS: The mean number of Gd enhancing lesions was higher during the pretreatment period than during treatment. This difference was statistically significant for the two different dose subgroups (3.5 v 1.8, P < 0.001 for the 3 MIU group and 2.4 v 0.9, P < 0.001 for the 9 MIU group, corresponding to a reduction of 49% and 64% respectively). The mean volume of Gd enhancing lesions also significantly decreased by 61% (3 MIU group) and 73% (9 MIU group). These reductions were evident only after the first month of treatment. The six-monthly rate of new lesions as seen in T2 weighted images showed a similar trend of reduction with treatment (65% and 70% respectively). Lesion volume on T2 scans significantly increased during the pretreatment period whereas it remained almost stable during the treatment period in both groups. Clinical relapse rate was significantly reduced by treatment (53% for the 3 MIU group, P < 0.001; 69% for the 9 MIU group, P < 0.001). CONCLUSION: Interferon-beta-1a seemed effective in reducing disease activity in relapsing-remitting multiple sclerosis at both the doses used.

Adolescent↗
PubMed1995

Clinical and MRI assessment of disease activity in patients with multiple sclerosis after influenza vaccination.

We investigated the possible effects of influenza vaccination on disease activity in multiple sclerosis (MS). Six patients were evaluated clinically during the year preceding and the year following influenza vaccination. Gadolinium-enhanced magnetic resonance imaging (Gd-MRI) was performed one day before and at days 15 and 45 after vaccination. Cumulatively, we did not observe increases in clinical or MRI disease activity following vaccination, with the exception of one case. This was the patient with the highest clinical disease activity during the year preceding vaccination. These results support and supplement previous observations, indicating that influenza vaccination is a safe procedure in multiple sclerosis. Nevertheless, it should be used with caution in patients with active/progressing disease.

Adult↗
PubMed1995

A controlled study of potential risk factors preceding exacerbation in multiple sclerosis.

A wide variety of potential risk factors for acute exacerbations in multiple sclerosis were evaluated in a one year case-control study. Eighty nine consecutive patients with clinically definite multiple sclerosis and relapsing remitting course presenting with a relapse between January and December 1992 were compared with patients matched for age, sex, and degree of disability, who did not experience clinical exacerbations during the same period. Only potential risk factors occurring in the three months preceding the interview were considered patients. Relapsing patients reported no significant increase in the frequency of any risk factor in the three month period before exacerbation compared with the control group. These results suggest that most relapses are not preceded by the conditions commonly considered as risk factors.

Adolescent↗
PubMed1995

Human recombinant interferon beta in the treatment of relapsing-remitting multiple sclerosis: preliminary observations.

An open comparative, randomized trial with recombinant human interferon beta (r-hIFN-beta) involving 72 patients with clinically definite and/or laboratory-supported relapsing-remitting MS is in progress at the University 'La Sapienza' and at the S. Camillo Hospital of Rome. After a 6 month period of clinical and magnetic resonance imaging (MRI) observation (baseline findings), patients are randomly assigned to one of two treatment groups receiving 3 or 9 MIU of recombinant human IFN-beta (r-hIFN-beta) self-administered by subcutaneous injection three times a week for 6 months. All patients are examined by MRI with and without gadolinium (Gd-DTPA) every 4 weeks for the entire duration of the study (12 months). The main aim of the study is to test the hypothesis that r-hIFN-beta may halt or slow the progression of the disease by showing a significant reduction in MRI activity. This will be achieved by comparing pre and post-treatment periods. As an additional clinical end point, the exacerbation rate during these two periods will be compared. This study began in June 1993 and the final analysis of MRI data is planned for the spring of 1995.

Adjuvants, Immunologic↗
PubMed1993

Predominant and stable T cell responses to regions of myelin basic protein can be detected in individual patients with multiple sclerosis.

T lymphocytes from patients with multiple sclerosis (MS) recognize multiple myelin basic protein (MBP) epitopes. This situation complicates the design of specific immunotherapies. We investigated to which extent the T cell response to MBP is heterogeneous in single subjects in terms of preferentially recognized regions of the molecule, major histocompatibility complex (MHC) restriction, and stability over time. From each of nine patients with MS, a minimum of six MBP-specific T lymphocyte lines (TLL) were assayed for the proliferative response to a panel of overlapping peptides, encompassing the whole MBP. Predominant T cell recognitions of distinct MBP regions were present in three patients, all HLA-DR2+, independently of the clinical features of their disease. T cell reactivity was preferentially directed to residues 16-38 in one patient. In this case the response was also stable over time, during different phases of the disease. Predominant reactivity to residues 86-99 was detected in the two other DR2+ patients. In each of the patients with other HLA-DR haplotypes (DR2-), as well as in three DR2+ non-MS donors, the T cell response to MBP appeared to be considerably more heterogeneous. The HLA restriction element varied among TLL recognizing the same MBP region, even when raised from the same individual. The genomic HLA typing, performed on the DRB1 and DRB5 genes in the DR2+ subjects, showed no obvious correspondence between preferential responses to regions of MBP and HLA-DR2 subtypes. In this context, a simple, new method for the genomic typing of the HLA-DRB1 gene in individuals with the HLA-DR2 serological specificity is also described. We conclude that predominant and stable T cell responses to a single MBP region can be detected in some patients with MS. In these individuals, the MHC restriction of the T cell recognition of predominant regions appears to be variable. Polymorphisms of the HLA-DR2 gene products alone do not account for the selection of the dominant MBP T cell epitope.

Adolescent↗
PubMed1993

Target epitopes of myelin basic protein specific T cell lines in multiple sclerosis.

A highly efficient new method for the generation of antigen specific T cell lines (TCL) is now available. By this method we established 134 myelin basic protein (MBP) TCL from the peripheral blood of 9 patients with definite multiple sclerosis (n = 69) and 8 healthy donors (n = 65). The yield of MBP reactive TCL in the two groups was comparable. So far 22 MBP specific TCL from 7 patients and 24 from 7 healthy individuals have been tested for their proliferative response to a panel of four synthetic peptides representing MBP residues 7-26, 80-99, 139-153 and 148-162. Although the peptide sequences did not encompass the whole MBP, the pattern of reactivity to these peptides in patients and controls seems to be similar. Further, when multiple TCL from the same donor were analysed, no dominant recognition emerged.

Adult↗
PubMed1993

New approaches to the study of T cell autoimmunity in multiple sclerosis. Meeting report on the 2nd Workshop on T cell Autoimmunity in MS, Perugia, Italy, 26-28 November, 1992.

This report discusses some of the papers presented during the 2nd T Cell Autoimmunity in MS Workshop held in Perugia on November 26-28, 1992. The 'trait d'union' of the meeting was the awareness that recent studies have failed to uncover clear-cut differences in T cell reactivity to autoantigens between patients with multiple sclerosis and healthy individuals. Hence, new strategies have been proposed to try to distinguish between 'pathological' autoimmunity in patients and 'natural' autoimmunity in healthy individuals. Furthermore, the studies have been extended to new potential autoantigens (myelin constituents other than myelin basic protein, superantigens, heat shock proteins) and new susceptibility genes such as those coding for transport-associated proteins (Tap-1 and Tap-2).

Autoimmune Diseases↗
PubMed1992

Multiple sclerosis patients express increased levels of beta-nerve growth factor in cerebrospinal fluid.

We describe the measurement of beta-nerve growth factor (NGF) content in cerebrospinal fluid (CSF) from multiple sclerosis (MS) patients compared with CSF from age-matched normal subjects using a specific sandwich immunoassay (ELISA). During acute attacks patients exhibit a significant increase of NGF content compared to controls. In contrast during remission the mean NGF levels in CSF markedly decrease. These results strongly indicate that increased NGF production in CSF is a characteristic feature of the MS inflammatory response.

Adolescent↗
PubMed1992

Tumor necrosis factor-alpha and interferon-gamma synthesis by cerebrospinal fluid-derived T cell clones in multiple sclerosis.

T cell clones derived from cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) were analysed for their capacity to produce interleukin 2 (IL-2), interleukin 4 (IL-4), interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). They were also compared with liver-infiltrating T cell clones from patients with chronic active hepatitis. All the CSF T clones (both CD4+ and CD8+) produced large amounts of IFN-gamma and particularly of TNF-alpha, that was synthesized in a significantly larger amount than compared clones. Moreover, they were capable of secreting IL-2, but not IL-4. From our results, we conclude that first, the CSF CD4+ T clones could constitute a subset with functional properties similar to the T helper 1 (Th1)/inflammatory cell subset of the mouse; and second, the large amounts of TNF produced by CSF T cell clones strongly suggests a significant role for this cytokine as well as of IFN-gamma in MS immunopathogenesis.

Adult↗
PubMed1992

T-lymphocyte reactivity to the recombinant mycobacterial 65- and 70-kDa heat shock proteins in multiple sclerosis.

Owing to their conservation and immunogenicity, heat shock proteins (hsps) represent a class of potential autoantigens. Moreover, they could be targets for gamma delta T lymphocytes, which are prominent in various immune disorders. We studied the T cell proliferative primary responses to recombinant M. bovis 65 kDa hsp (hsp65) and M. tuberculosis 70 kDa hsp (hsp70) in 31 patients with multiple sclerosis (MS), 19 patients with other neurological diseases (OND) and 19 healthy individuals. Positive responses to hsp70, but not to hsp65 were significantly more frequent in patients with MS than in patients with OND or in healthy individuals. In order to verify and refine these results and to characterize the hsp reactive T lymphocytes, we screened 147 PPD-specific long-term T cell lines (76 from 10 patients with MS and 71 from 12 healthy donors) for their proliferative response to hsp65 and hsp70. hsp70-reactive T lines were significantly more common in patients with MS than in healthy controls. The number of T lines responding to hsp65 increased in the MS group only slightly. In 19 T lymphocyte lines from patients with MS and healthy donors, a cytofluorometric analysis was performed with special attention paid to distinct T cell receptor gamma delta determinants. With one exception, in each line the population of gamma delta T cells remained a minority. We conclude that an increased T cell response to mycobacterial hsp70 may be present in patients with multiple sclerosis.

Adolescent↗
PubMed1992

Depression in the early phase of MS: influence of functional disability, cognitive impairment and brain abnormalities.

This study investigated the relationship between depression, physical disability, cognitive deficit and brain abnormalities on magnetic resonance imaging (MRI) in patients with early MS. Eighteen relapsing-remitting MS patients were evaluated: depression was diagnosed according to DSM-III R and measured by the MMPI depression subscale, physical disability was assessed by using the Kurtzke Expanded Disability Status Scale (EDSS) and cognitive functions by means of an extensive neuropsychological test battery. A neuroradiologist blinded to clinical findings quantified cerebral lesion on MRI. Weighted brain area lesion score were developed according to number and size of cerebral lesions. On the basis of DSM-III criteria, six patients were classified as having major depression, seven patients had minor depression and five patients were without depressive symptoms. No significant differences were found among the three groups on both neuropsychological performances and weighted MRI lesion scores. However patients with major depression exhibit greater physical disability than the other MS subgroups. A significant correlation was found between MMPI depression subscale and physical disability. This study suggests that at least in the early phase of MS, depression appears more related to the physical disability than to the severity of pathological brain involvement.

Activities of Daily Living↗
PubMed1992

Tumour necrosis factor-alpha synthesis by cerebrospinal-fluid-derived T cell clones from patients with multiple sclerosis.

T-cell clones derived from the CSF (cerebrospinal fluid) of MS (multiple sclerosis) patients have been analysed for the production of interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2) and interleukin-4 (IL-4). Each CSF-T clone (both CD4+ and CD8+) produced substantial amounts of IFN-gamma and especially TNF-alpha compared with autologous peripheral T clones and liver-infiltrating T clones from patients with chronic active hepatitis. The large quantities of TNF produced by CSF-T cell clones suggest an important role for this cytokine in MS immunopathogenesis.

Adult↗
PubMed1992

Hemianopic ataxic hemiparesis. A case report.

Ataxic hemiparesis and homonimous hemianopia developed in a hypertensive 60-year-old woman. Magnetic resonance imaging detected multiple lesions in the territory of distribution of the posterior cerebral artery and in the inferior region of the left cerebellar hemisphere. At computed tomography only a right hypodense area involving the posterior right thalamus, the postero-medial region of the temporal lobe and the occipital lobe was evident.

Ataxia↗
PubMed1991

Tumour necrosis factor-alpha synthesis by cerebrospinal-fluid-derived T cell clones from patients with multiple sclerosis.

T cell clones derived from cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) were analysed for their ability to produce interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2) and interleukin-4 (IL-4). The CSF-T clones were compared for their ability to produce cytokines with autologous peripheral T clones and with liver-infiltrating T cell clones from patients with chronic active hepatitis. IL-4 production was also compared with that by peripheral T clones derived from atopic patients. All the CSF-T clones (both CD4+ and CD8+) produced large amounts of IFN-gamma and particularly of TNF-alpha. These cytokines were synthesized in significantly larger amounts by CSF T clones than by reference clones. Moreover, they were capable of secreting IL-2, but not IL-4. We conclude that the CSF-CD4+ T clones could constitute a subset with functional properties similar to those of T helper 1 (Th1)inflammatory cells of the mouse; and that the large amounts of TNF produced by CSF T cell clones strongly suggest a significant role for this cytokine in MS immunopathogenesis.

Adult↗