Biomedical subjects

Roland Martin

Publications and source records attributed to Roland Martin.

57 records · Page 4Linked to original sources

PubMed1998

T-cell response to myelin basic protein and lipid-bound myelin basic protein in patients with multiple sclerosis and healthy donors.

An autoimmune T-cell response to myelin proteins is thought to be involved in the pathogenesis of multiple sclerosis (MS) and myelin basic protein (MBP) is the most widely studied potential target antigen. We investigated the T-cell response to MBP in MS patients and controls using two different molecular forms of the protein: the classical hydrophilic MBP (lipid-free MBP, LF-MBP) and a lipid-bound, native-like preparation of MBP isolated in a molecular form retaining the binding to all myelin lipids (lipid-bound-MBP, LB-MBP). Short term T-cell lines (TCL) were generated using either LF- or LB-MBP and tested for their reactivity to the in vitro stimulating antigen. No differences were detected between MS patients and healthy donors in the percentage of T-cell cultures responsive to the LF-MBP. In contrast, the number of LB-MBP reactive cultures was higher in MS patients than in controls. This difference was almost entirely due to the presence of high numbers of LB-MBP-specific TCL in MS patients which did not cross-react with LF-MBP and were not present in healthy subjects. LB-MBP may represent a novel antigen worth to be investigated in MS.

Cell Line↗

PubMedDate not supplied

Antigen-specific therapies in multiple sclerosis.

During recent years, many new therapies for human autoimmune diseases such as multiple sclerosis (MS) have been considered based on promising in vitro data or animal experiments. A number of them have proceeded to early clinical testing. However, very few finally advanced to approval by the regulatory agencies and are currently available to patients. The main reasons for failure were either lack of efficacy in humans and/or unexpected and untolerable adverse events. Although previous attempts toward antigen-specific immunomodulation have often been disappointing, these difficulties have led to renewed interest in therapies that aim at reestablishing tolerance to autoantigens at the level of either T cell-mediated or antibody-mediated immune responses or both. Such antigen-specific immunotherapies offer the prospect of correcting pathological immune reactivity against autoantigens in a highly specific and effective manner and also achievement of this goal with relatively little side effects. Here we will review the various approaches that are currently being considered for antigen-specific immunotherapies in MS.

Animals↗

PubMedDate not supplied

The immunopathogenesis of multiple sclerosis.

Multiple sclerosis (MS) is a T cell-mediated autoimmune disease that is triggered by unknown exogenous agents in subjects with a specific genetic background. Genes of the major histocompatibility complex class II region are the only ones that have been consistently associated with the disease. However, susceptibility is probably mediated by a heterogeneous array of genes, which demonstrate epistatic interactions. Furthermore, an infectious etiology of MS has been suggested, and it is likely that infectious agents shape the immune response against self-antigens. Composition of plaques, response to therapy, and data from animal models indicate that MS is mediated by myelin-specific CD4 T cells that, upon activation, invade the central nervous system and initiate the disease. Different patterns of tissue damage have been shown in active MS lesions, suggesting that the mechanisms of injury are probably distinct in different subgroups of patients. Heterogeneity in clinical characteristics, magnetic resonance imaging, and response to therapies support this notion. The experience gained during several pharmacological studies has improved our understanding of the pathogenesis of MS. New tools, such as gene expression profiling with cDNA microarrays and proteomics, together with advancements in imaging techniques may help us to identify susceptibility genes and disease markers, which may enable us to design more effective therapies and to tailor them according to different disease forms or stages.

Autoimmune Diseases↗