SEARCH · PubMed Health

Results for “AUTOIMMUNE DISEASES”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources

PubMed1990

Drugs in autoimmune diseases.

Autoimmune diseases arise when autoimmunity or the loss of self tolerance results in tissue damages. Many mechanisms have been proposed for the origin of autoimmunity, including immunologic, viral, hormonal and genetic factors. All known parts of the immunological network are involved in causing immunopathologic symptoms. Therefore, more or less specific immunosuppressants are widely used in the treatment of autoimmune disorders which range from organ-specific, i.e. Hashimoto's thyroiditis, to non-organ-specific or systemic diseases, i.e. systemic lupus erythematosus. Unspecifically acting cytostatics do not only suppress autoimmune reactions but also create severe side-effects due to the impairment of immune responses against foreign antigens, leading, for example, to an increased risk of infections. Moreover, the genotoxic activity of cytostatics might induce malignancies. Corticosteroids are clinically well known and very active agents for the management of acute symptoms but different side-effects limit their use in the treatment of chronic diseases. Cyclosporin A has been an important step forward to a more specific prevention of organ transplant rejections and to the therapy of some autoimmune disorders. Modern approaches to immunosuppression include monoclonal antibodies directed against a variety of different determinants on immunocompetent cells. Ciamexone and Leflunomide which are in early clinical and preclinical development, respectively, might be interesting new drugs. Future immunopharmacologic drug research and development should lead to more specific, low molecular weight, orally active and chemically defined immunosuppressive compounds with good tolerability under long-term treatment of autoimmune diseases.

Adrenal Cortex Hormones↗

PubMed1989

Pathogenic mechanisms in autoimmune diseases.

Autoimmunity may be initiated by a variety of mechanisms involving changes in autologous antigens or alterations in immune regulation. Autoimmune disease, the pathological consequence of an autoimmune response, depends principally upon the stimulation of helper/inducer T cells reactive with self-antigens. Such T cells direct the quantity and quality of the immune response by influencing the mixture of interleukins produced. Autoantibodies react with accessible cells and mediate injury directly or indirectly. Delayed hypersensitivity reactions indirectly damage tissues through the agency of lymphokines. Cytotoxic T cells penetrate tissue spaces and attack cells bearing requisite surface antigens complexed with the appropriate major histocompatibility complex product. Macrophages and NK cells, activated by lymphokines, have potential to augment tissue damage. These several mechanisms do not operate in isolation; rather, multiple processes act in unison in most autoimmune diseases.

Animals↗

PubMed1998

On the role of a possible dialogue between cytokine and TCR-presentation mechanisms in the regulation of autoimmune disease.

Autoimmune diseases are thought to occur through some weakness in an active process of autoregulation. Two different regulatory mechanisms have been proposed separately during the years: a "non-specific" mechanism, via Th1-Th2 non-specific cytokines, and a "specific" one-on-one mechanism, via presentation of peptides, i.e., T cell receptor (TCR) peptides, by the T cells themselves. Several anti-idiotypic models rely on the latter to explain the effects of "T-cell-vaccination" therapy. We present and analyse a model for the interaction between both regulatory mechanisms within an ensemble composed of Th1 and Th2 cells. Our model shows how both TCR presentation and non-specific Th1/2 signals can cooperate in the choice of the prevailing Th1 or Th2 response. We show how TCR presentation can foster regulation, without necessitating a particular "suppressor" agent, of the type that some have assumed to play a central role in the regulation of autoimmunity. Our results suggest an important role for the cells' sensitivities to Th1 and Th2 derived cytokines; only for certain sensitivity ranges, is it possible to switch dominance between subtypes. It is argued that memory is sustained via modulation of sensitivities to cytokines, not only to antigens. The results and hypotheses also suggest one possible reason for the known correlation between standard and autoimmune diseases. Several therapies and informative experiments are suggested. We argue, for example, that administering a non-relevant peptide while increasing the ratio between the clones reactive to it and other clones in the pancreas, might cure autoimmune diabetes. Moreover, we predict that disease could be prevented by administering an autoimmune peptide at an early age while forcing the system to react in a Th2 fashion.

Antigen-Presenting Cells↗

PubMed2004

Gene therapy for autoimmune diseases.

Autoimmune diseases are threatening an increasing number of patients in developed countries, representing one of the major causes of disability and an enormous social cost. Current therapies mainly treat the symptoms of autoimmune diseases and are only partially able to interfere with disease evolution, and therefore decrease the degree of physical impairment. Thus, the development of new therapeutic strategies is imperative. This review focuses on gene therapy, as one possible alternative approach to the treatment of autoimmune disorders. The potential of gene therapy to specifically target tissues affected by autoimmune aggression, and its ability to interfere with the destructive pathogenic process while providing functional replacement and fostering reparative mechanisms will be emphasized. Gene therapy studies in experimental models of diabetes, rheumatoid arthritis and multiple sclerosis are reviewed.

Arthritis, Rheumatoid↗

PubMed1980

H gene theory of inherited autoimmune disease.

Autoimmune disease in inbred mice is probably determined by co-dominant genes associated with both the major and minor histocompatibility loci. It is postulated that the genes involved are histocompatibility-antigen (H) genes themselves, which delete complementary clones in fetal life, in accord with Burnet's theory of clonal selection. Such deletions cause perturbations in the paratope-idiotope network reactions envisaged by Jerne. As well as having negative effects on immune-response capacity, the perturbations have positive effects, because the deletion of clones with specificity for the idiotopes of other clones permists immune responses which would otherwise be absent. Such perturbations can influence the chance of emergence of a forbidden clone by somatic mutations occurring in the V genes of dividing immunocytes and so can provide a genetic predisposition to autoimmune disease.

Animals↗

PubMed1999

Role of dendritic cells in the induction and maintenance of autoimmune diseases.

Autoimmune diseases are characterised by the loss of tolerance against self-determinants, activation of autoreactive lymphocytes and pathological damage to single or multiple organs. The mechanisms by which autoimmune responses are triggered and activation of autoreactive lymphocytes is initiated and maintained are not yet fully understood. Translocation of previously immunologically ignored antigens from the periphery to secondary lymphoid organs is probably a key step in the initiation of autoimmunity. Antigen transport and primary sensitisation of T lymphocytes is mainly mediated by dendritic cells which reside in peripheral non-lymphoid tissues and maintain a continuous gradient of antigens towards secondary lymphoid tissues. In the transgenic rat insulin promoter-glycoprotein model of autoimmune diabetes, dendritic cell (DC)-mediated antigen transport initiates an autoimmune response against a pancreatic neoself-antigen. Dose and timing of antigen delivery by DC and turnover of antigenic peptides presented by DC are the main parameters regulating the outcome of autoimmune diabetes in this model system. An important sequel of continued antigenic stimulation via DC is the formation of lymphoid structures in the pancreas. Thus, appropriate and repeated activation of cytotoxic T lymphocytes by DC, in concert with local inflammatory processes leading to formation of organised lymphoid tissue in the target organ, is likely to be crucial in the development of destructive autoimmunity. Therapeutic intervention to selectively manipulate antigen transport by dendritic cells or to influence antigen presentation may prove beneficial for the treatment of autoimmune diseases. Furthermore, the capacity of DC to induce potent antiself responses might have implications for the use of DC presenting self-antigens in treatment of established tumours.

Animals↗

PubMed2006

Can unresolved infection precipitate autoimmune disease?

Autoimmune diseases are frequently postulated to arise as post-infectious phenomena. Here we survey the evidence supporting these theories, with particular emphasis on Crohn's disease and ankylosing spondylitis. Direct proof that infection establishes persistent autoimmunity remains lacking, although it may provoke a prolonged inflammatory response when occurring on a susceptible immunological background. The argument of infective causality is by no means trivial, since it carries important consequences for the safety of vaccine development.

Animals↗

PubMedDate not supplied

Altered immunoendocrine dialogue in autoimmune disease.

Autoimmune diseases have a multifactorial pathogenesis including essential genetic and nonessential modulatory factors. Among the essential factors, not only should genes coding for an abnormal reactivity of the immune system be considered, but we have, in addition, provided experimental evidence for the existence of genes responsible for a susceptibility of the target organ/structure for the autoimmune attack. Only when both sets of essential genes are present does an autoimmune disease develop at all. The modulatory factors then determine the final outcome in each case. The present contribution discusses the immunomodulating role of glucocorticoid and sex steroids focussing on the Obese Strain (OS) of chickens, a model for Hashimoto thyroiditis.

Animals↗

PubMed2002

Systemic lupus erythematosus and related autoimmune diseases are antigen-driven, epigenetic diseases.

Autoimmune diseases result when cellular stresses (ex UV, cell cycle, hormones, viruses, and/or drugs) induce altered expression of polyamines, leading to chromatin disruption, interference with chromatin methylation, exposure of sequestered genes, and interference with tissue-specific processes. Exposure of previously sequestered Alu and LINE-1 sequences can lead to reverse transcription of Alu-RNA (and other transcripts) by the LINE-1 reverse transcriptase, yielding autoantigenic, hypomethylated DNA fragments. Release from the cell of the hypomethylated DNA fragments, along with polyamine-associated nucleoprotein complexes formed with the fragments, would elicit the autoimmune response. Loss of gene control due to hypomethylation and chromatin disruption by polyamines or other factors can include loss of dosage compensation from the inactive X chromosome for spermine synthase and spermidine/spermine N(1)-acetyltransferase at Xp22.1. This leads to ongoing altered polyamine levels. Thus, autoimmune diseases result from epigenetic changes that lead to autoantigen generation.

Autoantigens↗

PubMed1989

Use of DNA amplification methods for clinical diagnosis in autoimmune diseases.

Autoimmune disease is generally felt to result from the interaction of genetic and environmental factors. In recent years, significant advances have been made in using recombinant DNA methods to analyze specific genetic factors and infectious agents. However, new techniques are needed that are more rapid, inexpensive, and suitable for small tissue biopsies obtained early in the course of disease. New methods of DNA amplification based on polymerase chain reaction (PCR) and Q beta-replicase (Q beta R) have recently been reported. These methods are briefly reviewed, and their potential applications to patients with autoimmune disease are presented. Several types of applications can be considered, including detection of: a) specific HLA-D alleles in order to predict prognosis and better utilize existing medications; b) bacterial, fungal, and spirochete infections in joint aspirates or synovial biopsies; c) human immunodeficiency virus (HIV) and other viruses (e.g., EBV, CMV) that may be associated with immune dysregulation in certain patients; and d) neoplastic transformation in blood or tissues by determining monoclonal gene rearrangements, karyotypic alterations or oncogene activation. It is likely that routine clinical laboratories will soon begin implementing DNA amplification methods in order to screen blood products for infectious agents (especially HIV and hepatitis B virus). Because these techniques will be readily available, rheumatologists/clinical immunologists should begin developing strategies that will allow them to use these methods in a cost-effective manner for diagnosis and monitoring treatment.

Autoimmune Diseases↗

PubMed2006

Avian models with spontaneous autoimmune diseases.

Autoimmune diseases in human patients only become clinically manifest when the disease process has developed to a stage where functional compensation by the afflicted organ or system is not possible anymore. In order to understand the initial etiologic and pathogenic events that are generally not yet accessible in humans, appropriate animal models are required. In this respect, spontaneously developing models--albeit rare--reflect the situation in humans much more closely than experimentally induced models, including knockout and transgenic mice. The present chapter describes three spontaneous chicken models for human autoimmune diseases, the Obese strain (OS) with a Hashimoto-like autoimmune thyroiditis, the University of California at Davis lines 200 and 206 (UCD-200 and -206) with a scleroderma-like disease, and the amelanotic Smyth line with a vitiligo-like syndrome (SLV). Special emphasis is given to the new opportunities to unravel the genetic basis of these diseases in view of the recently completed sequencing of the chicken genome.

Animals↗

PubMed2002

Immunomodulatory effects and mechanisms of plant alkaloid tetrandrine in autoimmune diseases.

Autoimmune diseases characterized by activation of immune effector cells and damage of target organs are currently treated with a combination of several disease-modifying antirheumatic drugs (DMARDs) that preserve different immunomodulatory mechanisms. Such a combination treatment strategy not only provides synergistic effects but also reduces side effects from individual drug. Tetrandrine (Tet), purified from a creeper Stephania tetrandra S Moore, is a bis-benzylisoquinoline alkaloid and has been used to treat patients with silicosis, autoimmune disorders, and hypertension in Mainland China for decades. The accumulated studies both in vitro and in vivo reveal that Tet preserves a wide variety of immunosuppressive effects. Importantly, the Tet-mediated immunosuppressive mechanisms are evidently different from some known DMARDs. The synergistic effects have also been demonstrated between Tet and other DMARDs like FK506 and cyclosporin. These results highlight Tet a very potential candidate to be considered as one of DMARDs in the treatment of autoimmune diseases, especially rheumatoid arthritis. This review summarizes evidence-based in vivo and in vitro studies on this potential Chinese immunosuppressive herb.

Alkaloids↗

PubMed1989

Thymic abnormalities and autoimmune diseases.

Autoimmune diseases such as ulcerative colitis (UC) and myasthenia gravis (MG) are frequently associated with thymic abnormalities. Thymus hyperplasia and/or thymoma have been demonstrated in all cases with both of these two diseases by pneumomediastinography (PMG). In the diseases of digestive organs from which we can easily obtain the local information through the endoscopic observation and biopsy specimens, lots of immunological abnormalities have been accumulated. Antibody-dependent cell-mediated cytotoxicity mechanism has been demonstrated to play an important role in the mucosal destruction in UC. In the peripheral blood level of this disease, immunological abnormalities have been demonstrated such as the presence of lymphocytes sensitized by certain antigens, autoantibodies and disturbances of lymphocyte subpopulations. In the level of the thymus, the retrovirus has been detected in the thymus epithelial cells. The supernatant of thymus epithelial cell culture (STEC) has the capability of differentiating human bone marrow cells and of facilitating disease-specific immune abnormalities. Moreover, the serum factors (thymus growth factor) discovered in the patients with UC and MG, have been demonstrated to alter the thymic environments. Therefore, it is postulated that thymectomy is beneficial to exclude these abnormalities and it has been evaluated to be very effective in UC and MG clinically. From these observations, it is thought to be important to investigate the immunological abnormalities of autoimmune diseases from the viewpoints of three immunological levels, the level of disease-specific organ, the peripheral blood level and the level of the thymus. And it is important that the therapeutic plans should be decided in the consideration of the abnormalities in each immunological level.

Autoimmune Diseases↗

PubMed1997

Diagnosing and Treating the Predominantly Female Problems of Systemic Autoimmune Diseases.

Autoimmune diseases with rheumatic manifestations are predominantly diseases of women. Any woman with new onset arthralgia or arthritis should have a thorough history and physical to rule out autoimmune connective-tissue disease. Screening serologic tests, however, are not necessarily recommended because of high false-positive rates. Serologic tests are most useful in confirming or ruling out the diagnosis; for example, systemic lupus erythematosus (SLE) is rarely present when antinuclear antibodies (ANAs) are absent; the absence of rheumatoid factor will not rule out rheumatoid arthritis (RA), but its presence confirms it. Most autoantibodies (RF [rheumatoid factor], ANA, ENA [extractable nuclear antigen], anti-Jo-1, etc) do not vary with disease flare-ups and remissions. Plain radiographs of the joints are not useful except as a baseline and in detecting erosion at end of long bones associated with RA. Polymyalgia rheumatica and RA, with an incidence of 1 in 2000 to 3000, are the most common autoimmune disorders. Other autoimmune diseases such as SLE, vasculitis, polymyositis, and dermatomyositis are seen infrequently in general practice. Pregnancy, menopause, or breast implantation may affect disease prognosis and treatment. For example, in pregnancy, RA symptoms generally improve, whereas those of SLE may worsen; both diseases may flare postpartum. Oral contraceptives have been associated with an increase in disease flare-ups, but there is little or no evidence that estrogen in the dose level used for replacement is harmful to SLE patients. Although relatively rare, autoimmune diseases can be devastating to the patient if not promptly recognized and properly treated.

Journal Article↗

PubMed1998

Autoimmune diseases and autoimmunity post-bone marrow transplantation.

BMT can both transmit and eliminate autoimmune diseases, and hence it has been suggested as an optional treatment for severe autoimmune conditions. In this communication we deal with the question of whether chronic GVHD is an autoimmune disease in itself, review the literature reports of autoimmune diseases following BMT in humans, and describe the autoimmune nature of the post-BMT state. Chronic GVHD, which is a frequent complication post-BMT, has clinical and pathogenic characteristics similar to autoimmune diseases, such as scleroderma and Sjogren's syndrome. Although the pathogenesis of chronic GVHD is not yet clear, thymic damage induced by acute GVHD may contribute to both the immunodeficiency and autoimmunity characterising chronic GVHD. A similar phenomenon is syngeneic GVHD, which results from an imbalance between autoreactive and autoregulatory lymphocytes. Additionally, other autoimmune diseases have been reported in post-BMT patients, and among these the most common are hypothyroidism, hyperthyroidism, myasthenia gravis and immune cytopenias. Although these diseases also occur also outside the post-BMT setting, they are unique with respect to pathogenesis (no association between myasthenia gravis and thymic pathology), diagnosis (symptoms of hyperthyroidism may be inadvertently related to other conditions), and prognosis (post-BMT autoimmune cytopenias may be fatal and treatment non-responsive). Nevertheless, many other autoimmune diseases have been reported after BMT, and these are mainly presented as case reports. Regarding the mechanism of post-BMT autoimmunity, the minority of cases stem from donor-related transfer of pathogenic lymphocytes or their progenitors, while most of the cases (either chronic GVHD or specific diseases) can be attributed to the immunologic imbalances characterising the post-BMT setting. The factors that may expose an individual to autoimmunity development post-BMT include genetic predisposition, an environmental factor such as CMV, and the nature of the donor who may aid in creating microchimerism and subsequently chronic GVHD and its related autoimmune manifestations.

Autoimmune Diseases↗

PubMed2003

Origin of late-onset autoimmune disease.

Autoimmune disease in the elderly is hypothesized to be caused by an imbalance in T-cell expansion and deletion after an encounter with self-antigens. A decrease in thymic output leads to a decreased pool of naive T cells in the periphery and to increased oligoclonal expansion of T cells. This expansion may be caused by stimulation with autoantigens that drive high-affinity interactions with self-antigens. Accumulation of presenescent, apoptosis-resistant, and proinflammatory T cells results in the growth of these autoreactive T cells. A decreased T-cell activation response that occurs with age leads to several defects that diminish the immune response.

Age of Onset↗

PubMed2002

The natural killer cell -- friend or foe in autoimmune disease?

Autoimmune diseases are chronic conditions resulting from a loss of immunological tolerance to self-antigens. Recent observations have supported an ever-broader role for innate immune responses in directing and regulating adaptive immunity, including responses to self. This review summarizes recent findings supporting important functions of natural killer (NK) cells in regulating autoimmunity. A close survey of the current literature reveals multiple steps where NK cells can regulate inflammation and intervene in loss of self-tolerance. Importantly, the findings also caution against inferring a similar role for NK cells in all autoimmune phenomena or during separate stages of the same disease. Indeed, NK cells may have different influences during the priming and the effector phases of disease. Hence, an increased understanding of the involvement of NK cells in inflammation and infection should provide new insights into the pathogenesis of autoimmune disease.

Animals↗

PubMed1996

Interferon-gamma is required during the initiation of an organ-specific autoimmune disease.

Autoimmune gastritis induced by neonatal thymectomy of mice is a CD4+ T cell-mediated organ-specific autoimmune disease. The characteristic features of autoimmune gastritis, which include a mononuclear infiltrate within the gastric mucosa, loss of parietal and chief cells and circulating autoantibodies to the gastric H+/K+ ATPase, appear 6-10 weeks after thymectomy. Here we have assessed the role of interferon-gamma (IFN-gamma) in the pathogenesis of the gastric lesion. Splenic T cells derived from mice with gastritis produced three- to tenfold more IFN-gamma than T cells from normal animals after stimulation with anti-CD3 antibodies. Treatment of neonatally thymectomized mice at weekly intervals for 6 or 12 weeks with a neutralizing rat monoclonal antibody to mouse IFN-gamma abolished the production of anti-gastric autoantibodies and decreased the incidence of gastric mononuclear infiltrates from the 69% observed in normal rat immunoglobulin (Ig)-injected mice to 16%. Further, in mice treated with only a single dose of anti-IFN-gamma immediately after thymectomy at 3 days after birth, the incidence of autoimmune gastritis was 1/19 compared to 8/19 in normal rat Ig-injected mice. Prevention of autoimmunity by neutralization of IFN-gamma several weeks prior to the detection of a pathological lesion strongly suggests that IFN-gamma plays an essential role in the initiation of the gastric autoimmune response.

Animals↗