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Biomedical subjects

G Ristori

Publications and source records attributed to G Ristori.

At least 19 recordsLinked to original sources
PubMed2006

Multiple sclerosis: pharmacogenomics and personalised drug treatment.

Multiple sclerosis (MS) is a disorder of the central nervous system with an inflammatory and a neurodegenerative component. We do not yet have a definitive therapy for MS. Attempts to develop new treatments are long and costly and should be paralleled by studies aimed at increasing the therapeutic index of the existing treatments, interferon beta and glatiramer acetate. Pharmacogenetics and pharmacogenomics may be of use in this respect though their application may not be straightforward, particularly in MS.

Humans↗
PubMed2004

Relationship between emotional distress in caregivers and health status in persons with multiple sclerosis.

Caregivers of persons with multiple sclerosis (MS) exhibit less satisfaction with quality of life with respect to the general population. To assess the relationship between depression in caregivers and health status profiles of MS patients, we examined data from 133 patients and their respective caregivers, as a part of a prospective randomized trial aimed to investigate the effectiveness of home-based care. Patients were evaluated at baseline and one year later with measures of physical and psychological impairment and health status (SF-36 Health Survey). Caregivers' psychological morbidity was assessed by the Profile of Mood State (POMS) at the same time points. An improvement of patients' health status as measured in four out of eight SF-36 dimensions was observed over the study period, while psychological morbidity of their caregivers did not change significantly. Depression in caregivers was related to physical, emotional and health status of the patients at baseline and/or at 12-month follow-up. Changes in the degree of depression of caregivers were also associated with changes in disability and health status of the patients. This study confirms and extends in a home-care setting previous findings on relationships between patients' status and depression in caregivers. It suggests that the caregiver is an appropriate and independent target for more focused therapeutic strategies.

Adult↗
PubMed2003

Physiopathology of multiple sclerosis.

Pleiotropy and redundancy are distinctive elements of the immune response. Recent research into the inflammatory component of multiple sclerosis (MS) indicates that, as expected, pleiotropy and redundancy characterize various physiopathological mechanisms of the disease. A certain degree of redundancy is becoming apparent also as far as the degenerative component is concerned. Cumulatively, these data suggest that treatments that target single pathogenetic pathways are unlikely to provide a definitive solution. Combination therapies may offer, in principle, some advantage, although there is a need for more information on the aetiology of the disease.

Animals↗
PubMed2002

Home based management in multiple sclerosis: results of a randomised controlled trial.

BACKGROUND: Home based medical care is a popular alternative to standard hospital care but there is uncertainty about its cost-effectiveness. OBJECTIVES: To compare the effectiveness and the costs of multidisciplinary home based care in multiple sclerosis with hospital care in a prospective randomised controlled trial with a one year follow up. METHODS: 201 patients with clinically definite multiple sclerosis were studied. They were randomised in a ratio 2:1 to an intervention group (133) or a control group (68). They were assessed at baseline and one year after randomisation with validated measures of physical and psychological impairment and quality of life (SF-36 health survey). The costs to the National Health Service over the one year follow up were calculated by a cost minimisation analysis. RESULTS: There were no differences in functional status between the home based care group and the hospital group. There was a significant difference between the two groups favouring home based management in four SF-36 health dimensions-general health, bodily pain, role-emotional, and social functioning (all p < or = 0.001). The cost of home based care was slightly less (822 euros/patient/year) than hospital care, mainly as a result of a reduction in hospital admissions. CONCLUSIONS: Comprehensive planning of home based intervention implemented by an interdisciplinary team and designed specifically for people with multiple sclerosis may provide a cost-effective approach to management and improve the quality of life.

Adult↗
PubMed2001

T cell response to N-formylated peptides in humans.

We present the first evidence of a T lymphocyte response to N-formylated peptides in humans. N-formylated peptide sequences from self (mitochondrial) and foreign (microbial) antigens were used to isolate antigen-specific T cell clones from healthy individuals, including a set of monozygotic twins. The observed response differed from that previously described in mouse (CD4(+) phenotype and MHC class II restriction in humans vs. CD8(+) phenotype and class I restriction in mice). These lymphocytes produce substantial amounts of IFN-gamma. They were isolated in only one of the monozygotic twins, which suggests that their expansion in the healthy immune repertoire is independent of the genetic background. Our result will help in assessing the relevance of N-formylated peptide-specific T cells in protection against infections within the human immune system.

Adult↗
PubMed2000

Myelin basic protein intramolecular spreading without disease progression in a patient with multiple sclerosis.

A case with stable multiple sclerosis (MS) and T cell responses which initially focused on peptide 16-38 of myelin basic protein (MBP) allowed us to investigate the dynamics of the MBP-specific T cell repertoire and its relationship with disease progression. Epitope mapping experiments and T cell receptor usage of MBP-reactive T cell lines (obtained at four distinct time points over a 7-year period) showed a spreading of the response. Transient expansions and persistence of T cells recognizing different MBP epitopes were also detected. The patient's expanded disability status scale and magnetic resonance imaging lesion load remained stable. Our case shows both persistent self-recognitions and determinant spreading in stable MS. This finding suggests that the relationship between dynamics of self-recognition and disease progression is highly complex.

Adult↗
PubMed2000

Global immune disregulation in multiple sclerosis: from the adaptive response to the innate immunity.

Increasing evidences show a global immune disregulation in multiple sclerosis (MS). The possible involvement of myelin and non-myelin (auto-)antigens in the autoaggressive process as well as the disregulation of both adaptive and innate immunity challenge the concept of specific immunotherapy. T cells at the boundary between innate and adaptive immunity, whose immunoregulatory role is becoming increasingly clear, have recently been shown to bear relevance for MS pathogenesis. Global immune interventions (and type I interferons may be considered as such) aimed at interfering with both innate and acquired immune responses seem to be a most promising therapeutic option in MS.

Humans↗
PubMed2000

Evidence for a role of gammadelta T cells in demyelinating diseases as determined by activation states and responses to lipid antigens.

In this report we review current information on the phenotypic and functional properties of gammadelta T cells in demyelinating disorders. The results support the conclusion that although gammadelta T cells show evidence of activation in patients with either multiple sclerosis (MS) or Guillain Barrè syndrome (GBS), differences exist in the phenotypic and functional properties of these cells between the two diseases. In particular, our data indicate that in patients with MS the Vdelta2 subset is activated and that these cells can be induced to secrete high levels of proinflammatory cytokines. In contrast, in patients with GBS, the Vdelta1 subset is expanded and can be induced to secrete cytokines more associated with a humoral response.

Guillain-Barre Syndrome↗
PubMed2000

Twins: mirrors of the immune system.

Twin studies are a powerful tool to assess genetic and nongenetic factors in multifactorial, immune-mediated diseases. Here, Marco Salvetti and colleagues review important results from such studies and highlight their potential value. Future developments that should help to realize the potential of twin studies are discussed.

Humans↗
PubMed2000

Compositional bias and mimicry toward the nonself proteome in immunodominant T cell epitopes of self and nonself antigens.

We investigated whether and how molecular mimicry affects the shaping of the helper T cell repertoire. We implemented an algorithm that measures the probability of mimicry between epitopes of known immunogenicity and self or nonself proteomes. This algorithm yields 'similarity profiles', which represent the probability of matching between all contiguous overlapping peptides of the antigen under examination and those in the proteome(s) considered. Similarity profiles between helper T cell epitopes (of self or microbial antigens and allergens) and human or microbial SWISSPROT collections were produced. For each antigen, both collections yielded largely overlapping profiles, demonstrating that self-nonself discrimination does not rely on qualitative features that distinguish human from microbial peptides. However, epitopes whose probability of mimicry with self or nonself prevails are, respectively, tolerated or immunodominant and coexist within the same (auto-)antigen regardless of its self/nonself nature. Epitopes (on self and nonself antigens) can cross-stimulate T cells at increasing potency as their similarity with nonself augments. Mimicry, rather than complicating self-nonself discrimination, assists in the shaping of the immune repertoire and helps define the defensive or autoreactive potential of a T cell. Being a predictor of epitope immunogenicity, it bears relevance to vaccine design.

Algorithms↗
PubMed2000

An attempt of identifying MS-associated loci as a follow-up of a genomic linkage study in the Italian population.

Subsequent to a genomic linkage study on Sardinian and Continental Italian families, we considered the possibility that some of the tested microsatellite markers showed association to MS. Markers selected on the basis of the data obtained in the original set of 70 multiplex families were tested for MS association in an additional set of 154 simplex families. A limited set of markers were further tested on an additional set of 100 simplex families. The results indicate the presence of a putative MS gene in 19q13.13.

Alleles↗
PubMed2000

Dynamics of the reactivity to MBP in multiple sclerosis.

Though many lines of evidence support the importance of myelin basic protein (MBP) in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), its role in multiple sclerosis (MS) is still debated as well as the significance of epitope spreading in disease progression. We characterised the response to MBP in eight MS subjects and three of these were followed over time. In one case, the follow up lasted over a 6-year period. Clonal expansion, clonal persistence and epitope spreading against other MBP determinants was detected irrespective of disease course. In one patient we identified a novel T-cell receptor variable gene (BV28S2) which may be involved in the selection of MBP determinants, as suggested by experiments performed in the presence of mismatched antigen presenting cells (APC) between two subjects compatible for HLA-DR2 subtype but differing for the epitope recognised. Our findings do not sustain a role for the response to MBP effecting on clinical course and suggest that a novel TCR gene may be involved in the recognition of unusual self antigens.

Amino Acid Sequence↗
PubMed1999

Use of Bacille Calmette-Guèrin (BCG) in multiple sclerosis.

We studied the effect of Bacille Calmette-Guerin (BCG) vaccine as an immunomodulator in MS. According to the guidelines for clinical trials in MS, a single crossover, MRI-monitored trial was performed in 14 patients with relapsing-remitting MS. After treatment, MRI activity was significantly reduced. No major adverse effects were reported. Adjuvant therapy with BCG vaccine was safe and merits study in MS.

Adjuvants, Immunologic↗
PubMed1999

T cell response to myelin basic protein before and after treatment with interferon beta in multiple sclerosis.

Studies on the in vivo effects of interferon-beta (IFNbeta) therapy on autoreactive T cells have never been carried out in multiple sclerosis (MS). We investigated the T cell response to myelin basic protein (MBP), before and after IFN-beta therapy, raising MBP-specific T cell lines (TCL) from the peripheral blood of six MS patients with a satisfactory response to the treatment. IFNbeta did not affect the relative frequency and epitope specificity of the TCL. After IFNbeta therapy, the production of interleukin-4 was decreased in MBP-stimulated TCL while the secretion of interferon-gamma was increased in unstimulated TCL. Interleukin-10 and tumor necrosis factor-alpha did not show significant variations. This finding supports recent suggestions about the complexity of the T helper 1/T helper 2 paradigm in MS and other organ-specific autoimmune diseases. In fact, the beneficial effects of IFNbeta do not exclude an immunostimulatory action that may involve potentially autoreactive T cells. This has implications for future treatment options, including combination therapies.

Adult↗
PubMed1999

A major influence of the T cell receptor repertoire as compared to antigen processing-presentation in the selection of myelin basic protein epitopes in multiple sclerosis.

We selected two multiple sclerosis (MS) patients, compatible for HLA-DR2 subtype, and differing for HLA-DM haplotype as well as for the myelin basic protein (MBP) epitope recognized by the vast majority of their T cell lines (TCL) (residues 16-38 and 86-99, respectively). TCL sharing the same restriction element were re-assayed in the presence of reciprocally mismatched antigen-presenting cells (APC). The TCL recognized both the whole MBP and the relevant peptide also in the presence of non-autologous APC, (compatibility for processing, despite a difference in the DM haplotype). The same protocol, performed in serum-free pulsing experiments or in the presence of 'fixed' APC, excluded extracellular processing or mutual T cell presentation, and confirmed the need for MBP processing in our system. The finding, that only TCL recognizing MBP peptide 16-38 (a region not previously related to the DR2 haplotype) used a novel Vbeta, supports the importance of the TCR repertoire over the processing-presentation machinery in the selection of MBP epitopes in MS.

Antigen-Presenting Cells↗