1,721,108 research outputs found
[The current outlook in the therapy of autoimmune diseases]
No full textRecent advances in immunology and molecular biology have contributed to a much greater understanding of the pathogenetic mechanisms of the autoimmune diseases and thus to the development of new rationally-based therapies. Most of the immunosuppressive agents that have been tried in autoimmune disease patients nonspecifically suppress the immune response, often causing various side effects. Autoimmune diseases result from the activation of self-reactive T cells that recognize autoantigens or foreign antigens cross-reactive with an autoantigen coupled with major histocompatibility complex (MHC) products on an antigen presenting cell. It appears possible to modulate T cell activation by interfering with the interaction between T cell receptor and the peptide-MHC molecule complex. A number of sites are potential targets for immunologic intervention, such as MHC molecules, T cell receptor, CD4 and CD3 molecules, adhesion molecules, cytokines and cytokine receptors. In the present review the most important new therapeutic approaches to autoimmune conditions, which appear to be more selective in overcoming the limitations of non-specific treatments, are summarized. They include monoclonal antibodies, cytokines and cytokine-inhibitors, peptides interacting with MHC molecules and T cell vaccination
Immunogenetic studies on systemic lupus erythematosus
No full textUnderstanding the pathogenesis of systemic lupus erythematosus (SLE) remains a considerable challenge. Multiple abnormalities of both the innate and adaptive immune system have been described and, furthermore, immunological dysfunction precedes clinical presentation by many years. There is a strong genetic basis to SLE, which means that genetic studies can play a key role in furthering our understanding of this disease. Because susceptibility variants are present from birth and are unaffected by the course of the disease, or by its treatment, genetic analysis is, perhaps uniquely, capable of identifying fundamental, causative, disease mechanisms. In this article, we review our SLE immunogenetic studies performed in collaboration with the European Working Party on Systemic Lupus Erythematosus. By considering the results of our research and the recent advances obtained by genome-wide associations' studies, we can begin to understand how dysregulation at a number of key immunological steps may predispose to the development of SLE
Infection-genetics relationship in systemic lupus erythematosus
No full textGenetic, environmental, and hormonal factors contribute to disease susceptibility in systemic lupus erythematosus. Among environmental factors, infectious agents play a major role. When considering the complex relationship between genetic predisposition and infections in the pathogenesis of systemic lupus erythematosus, we have to consider that infectious agents can interact with the immune system in several ways. For example, molecular mimicry, altered apoptosis of the host cells, exposure of as yet masked antigens to the immune system by a given microorganism, and direct viral invasion of immunocompetent cells are all mechanisms that may give rise to dysfunction of the immune system; in addition, some genetically determined deficit of the immune system, such as complement deficiency or deficit of mannose binding lectine, may cause insufficient clearance of infectious agents, whose persistence in the host may determine autoimmunity. Finally, evidence has been emerging suggesting that the production of autoantibodies, by infected B-lymphocytes, may be drawn by altered expression of particular microRNA in these cells. In this paper, we review some of the distinct scenarios that can account for the role of infectious agents, acting on a genetically prone host, in determining systemic lupus erythematosus
Function of the HLA class I and II molecules: Relationship with autoimmunity [Funzione delle molecole HLA di classe I e II: correlazioni con l'autoimmunità]
No full textMajor histocompatibility complex (HLA in humans) encodes membrane proteins which play a very important role in the activation of the immune system. Besides the well known class I molecules (HLA-A, B, C) and class II molecules (HLA-DR, DQ, DP), loci have been discovered whose products are involved in antigen processing and presentation, such as the 'peptide transporter genes' and the 'proteasomes'. In addition, MHC-encoded heat shock proteins may be involved in delivering peptides to class II molecules and to membrane transport proteins which pump peptides into the endoplasmic reticulum for coupling with class I molecules, and the regulatory promotor regions of HLA class II molecules influence the transcriptional levels of the structural genes. MHC is equivalent to an eukaryotic operon encoding a complete kit for the processing and presentation of antigens to T lymphocytes. This kit includes various sets of genes for molecules with distinct functions. Various degrees of polymorphism exist in all these classes of genes. These polymorphisms could contribute to the disease associations at present attributed to the MHC glycoproteins
Capillary microscopy: Association of two distinct patterns of capillary alterations in an overlap syndrome
No full textPneumocystis carinii pneumonia complicating selective CD4 T cell depletion induced by corticosteroid therapy in a patient with systemic lupus erythematosus
No full text[Diffuse idiopathic skeletal hyperostosis of the cervical spine in a patient with ankylosing spondylitis. Description of a personal case]
No full textDiffuse idiopathic skeletal hyperostosis (DISH) is a well-described disorder of middle-aged people, with a unique spinal pathology characterized by calcification and ossification of the antero-lateral aspect of at least four contiguous vertebral bodies, with the sparing of intervertebral spaces and sacroiliac joints. DISH has rarely been reported associated with ankylosing spondylitis (AS), a chronic inflammatory articular disease most commonly involving the spine and sacroiliac joints. A 63-year-old man with clinical and radiological findings of DISH with associated AS is described here. The authors conclude that these two diseases may, albeit rarely, coexist
Safety of anti-tumor necrosis factor agents in rheumatic potential carriers of occult hepatitis B virus
No full textThe Immunogenetics of the Antiphospholipid Syndrome, Anticardiolipin Antibodies, and Lupus Anticoagulant
No full textWhether a genetic predisposition to develop the antiphospholipid syndrome (APS) and to produce anticardiolipin antibodies (aCL) and lupus anticoagulant (LAC) exists has been addressed by family studies and by population studies on primary APS and on aCL in diseases other than primary APS. Various studies suggest a familial occurrence of aCL and LAC, with or without clinical evidence of APS. This familial tendency could be genetically determined, because APS, aCL, and LAC occur in families carrying haplotypes which contain HLA-DR4, -DR7, and -DRw53. Population studies on primary APS also indicate that HLA genes have a role in conferring susceptibility to develop primary APS. Again, DR4, DR7, and DRw53 are the relevant loci. Population studies on aCL in diseases other than primary APS indicate that aCL are associated with DR4, DR7, and DRw53, at least when they are found in patients with systemic lupus erythematosus. Because HLA-DR4, -DR7, and -DRw53 are in linkage disequilibrium, the genetic association of aCL could be with DRw53 and, depending on the regional frequency of DR4 or DR7, it could be linked with either DR4 or DR7. HLA-DR4 seems to be more important in Anglo-Saxons, whereas DR7 emerges in populations of Latin origin. In this report we review our studies and the pertinent literature in this field
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