Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003873 (rheumatoid arthritis)
 53,068 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oral tolerance (OT) has worked well in numerous laboratory animal models of autoimmune diseases. Humans have been orally tolerized to keyhole limpet hemocyanin (KLH); patients with systemic sclerosis (SSc, scleroderma) have been orally tolerized to oral type I collagen (CI). However, clinical trials of oral type II collagen (CII) therapy in rheumatoid arthritis (RA) have had mixed results. Clinical studies show that compounds (such as nonsteroidal antiinflammatory drugs and prednisone) that inhibit generation of PGE(2) block OT induction. In murine OT models, the PGE(1) analog, misoprostol, reverses the NSAID OT block. These animal studies suggest that OT to CII or other antigens in patients with RA should be inducible if measures are taken to maintain normal prostaglandin function in the gut- associated lymphoid tissue (GALT). A clinical trial is underway in patients with RA to assess whether withholding NSAIDs and prednisone will allow OT to to be induced, and whether oral CII has meaningful clinical efficacy in this disease.
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PMID:Can we induce tolerance in rheumatoid arthritis? 1117 72

Sterols and sterolins, also known as phytosterols, are fats present in all plants, including fruits and vegetables. Although they are chemically similar to the animal fat, cholesterol, they have been shown to exert significant unique biochemical effects in both animals and humans. Because they are bound to the fibers of the plant, they are difficult to absorb during the transit of digested food through the gut, particularly in individuals with impaired digestive function. For this reason, and because much of the modern diet is over-processed and low in fresh plant materials, sterols and sterolins appear in the serum and tissue of healthy humans at 800-1000 times lower concentrations than that of cholesterol. Beta-sitosterol (BSS) is the major phytosterol in higher plants along with its glycoside, beta-sitosterolin (BSSG). Animal studies have demonstrated BSS and BSSG possess anti-inflammatory, antipyretic, antineoplastic, and immune-modulating properties. In other in vitro, animal, and human studies, a proprietary BSS:BSSG mixture has shown promise in normalizing T-cell function, dampening overactive antibody responses, and normalizing DHEA:cortisol ratios. Research has shown plant oils contain the highest concentration of phytosterols, nuts and seeds contain moderate amounts, and fruits and vegetables generally contain the lowest phytosterol concentrations. Because only low levels of these substances are found in humans, increased dietary intake of unprocessed fruits and vegetables or supplementation with commercial phytosterols may be of benefit in re-establishing optimal immune parameters. Restoring balance to the immune system may be of therapeutic benefit in disease processes such as chronic viral infections, stress-induced immune suppression, tuberculosis, allergies, cancer, and rheumatoid arthritis and other autoimmune conditions.
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PMID:Monograph. Plant sterols and sterolins. 1130 82

Reactive arthritis was initially described as a sterile synovitis, without microbial components present in the joint tissue. It has, however, become evident that bacterial degradation products, and even bacterial DNA, are present in the synovium of patients with this disease. Since intestinal pathogens are important causes of reactive arthritis, and since cellular homing allows transport of bacterial products from the gut to synovium, we have approached the etiology of rheumatoid arthritis from this point of view. A series of observations has led to a hypothesis that patients with rheumatoid arthritis might favour, for genetic reasons, intestinal bacteria which are capable of inducing arthritis. In the long-run, with continuous seeding of bacterial products from the gut, the synovial inflammation is followed by erosion, exposition of cartilage antigens, and autoimmunity.
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PMID:From reactive arthritis to rheumatoid arthritis. 1133 6

Gut ischemia-reperfusion (G-IR) induces a systemic inflammatory response, in which leukocyte contribution to this injury in distant organs is important. ICAM-1 as well as CD11/CD18 have been involved in leukocyte infiltration in liver and lungs. CD44 adhesion molecule plays an essential role in other inflammatory processes such as rheumatoid arthritis and allergic contact dermatitis, however its implication in G-IR has not been described. In order to establish a possible role of CD44 in the development of systemic inflammation by G-IR, we have studied CD44 mRNA expression by RT-PCR in a murine model of gut ischemia reperfusion. Animals subjected to G-IR showed an increased number of CD44 variable isoforms expressed in liver and spleen compared to non-treated animals or animals subjected to laparotomy. This finding indicates that G-IR specifically induces the expression of different CD44 variable isoforms. Liver CD44 upregulation in animals subjected to G-IR suggests a contribution of this molecule to lymphocyte activation and migration to this injured organ. Moreover, increased isoform expression in spleen may be induced by the proinflammatory environment resulting from a systemic depuration activity.
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PMID:[Isoforms modulation of CD44 adhesion molecule in a murine model of ischemia and intestinal reperfusion]. 1143 5

The objective of this study was to investigate CD163+ macrophages in the synovial membrane of patients with spondyloarthropathy (SpA). Immunohistochemistry was performed on synovium of 17 SpA and 18 rheumatoid arthritis (RA) patients, on colonic biopsies of 16 SpA patients and ten healthy controls, and on paired synovial biopsies of eight SpA patients, before and after anti-TNFalpha therapy. Phenotype and cytokine production were analysed by flow cytometry. CD163+ macrophages were increased in the synovial lining and sublining in SpA versus RA, as well as in colonic lamina propria in SpA versus controls. The number of CD163+ macrophages in the synovial sublining correlated with C-reactive protein levels and erythrocyte sedimentation rate. Paralleling the increase of CD163, HLA-DR was increased in the synovial lining and sublining of SpA. In contrast, the co-stimulatory molecules CD80 and CD86 and the dendritic cell markers CD1a and CD83 were scarce in SpA synovium. Flow cytometry indicated that CD163+ macrophages expressed high levels of HLA-DR and could produce in vitro tumour necrosis factor alpha (TNFalpha) but not interleukin-10 (IL-10). Finally, anti-TNFalpha therapy in vivo induced a decrease of CD163+ macrophages in the synovial lining and sublining. In conclusion, macrophages expressing the scavenger receptor CD163 are increased in synovium and in colonic mucosa in SpA, highlighting the relationship between joint and gut in this disease. The correlation with inflammatory parameters, the expression of HLA-DR, the production of TNFalpha but not IL-10, and the reduction by anti-TNFalpha therapy support a role for CD163+ macrophages in the synovial inflammation in SpA.
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PMID:Macrophages expressing the scavenger receptor CD163: a link between immune alterations of the gut and synovial inflammation in spondyloarthropathy. 1185 99

Epidermolysis bullosa acquisita is an autoimmune blistering disease of the skin characterized by IgG autoantibodies against type VII collagen. Systemic diseases are often associated with epidermolysis bullosa acquisita, Crohn's disease being the most frequent. This study sought to determine if type VII collagen, the epidermolysis bullosa acquisita autoantigen, was present in normal human colon by western blotting and immunofluorescence. The 290 kDa type VII collagen alpha chain was demonstrated by western blotting in four normal intraoperative colon specimens. Antibodies to type VII collagen labeled the junction between the intestinal epithelium and the lamina propria. We also used an enzyme-linked immunosorbent assay to test sera from patients with Crohn's disease (n = 19), ulcerative colitis (n = 31), celiac disease (n = 17), rheumatoid arthritis (n = 15), and normal controls (n = 16). It was found that 13 of 19 patients with Crohn's disease and four of 31 patients with ulcerative colitis demonstrated reactivity to type VII collagen. Sera from control subjects, patients with celiac disease or rheumatoid arthritis were negative. The sera from Crohn's disease patients also reacted with type VII collagen by immunoblot analysis. It was concluded that patients with inflammatory bowel disease may have IgG autoantibodies to type VII collagen, which exists in both the skin and the gut.
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PMID:The epidermolysis bullosa acquisita antigen (type VII collagen) is present in human colon and patients with crohn's disease have autoantibodies to type VII collagen. 1206 Apr 3

On August 14, 2001, a 76-year-old woman with a history of rheumatoid arthritis was admitted to our hospital with fever, cough, dyspnea and diarrhea. On admission, her chest radiography showed pleural effusion on the right side, and thoracocentesis was used to diagnose empyema. The patient underwent pleural drainage and received antibiotics. Alpha-Streptococcus was detected in both aerobic and anaerobic cultures of the pleural effusion. After 2 weeks of therapy, her empyema had improved; but her diarrhea, which had started 1 week before admission, had worsened, and her hypoproteinemia had progressed. Examination of the fecal clearance of alpha-1-antitrypsin and biopsied rectal material revealed that the diarrhea was caused by protein-losing enteropathy due to gastrointestinal amyloidosis secondary to rheumatoid arthritis. The patient was treated with steroids, but developed an additional infectious disease and died on September 29, 2001. In this case, she suffered from various infectious diseases including empyema and fungus infections. It has been reported that protein-losing enteropathy accompanies abnormalities in the immune system, by the loss of immunoglobulins and lymphocytes from the gut. We therefore suspect that protein-losing enteropathy due to gastrointestinal amyloidosis caused this patient's empyema.
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PMID:[An autopsy case of protein-losing enteropathy due to gastrointestinal amyloidosis, occurring in empyema]. 1260 5

Genes whose products play a critical role in regulation of the immune response include the human leucocyte antigen (HLA) and cytokine families of genes. The HLA genes are the most polymorphic found in the human genome, and the bulk of this polymorphism results in functional differences in expressed HLA molecules, resulting in inter-individual differences in presentation of peptide antigens to T-cells. In addition, a considerable number of cytokine-associated gene polymorphisms have been identified, the bulk of which occur in the upstream promoter sequences of these genes, which in many cases results in differential in vitro expression of the respective pro- or anti-inflammatory gene product. Particular HLA polymorphisms result in well-defined associations with a large number of immunologically-mediated diseases, including some diseases with known dietary risk factors. For example, individuals of HLA-DQA1*0501, DQB1*0201 genotype have a greater than 200-fold increased risk of developing intolerance to dietary wheat gluten (coeliac disease), and additional HLA-related factors may influence the development of malignant lymphoma within pre-existing coeliac disease. Similarly, HLA-DRB1 alleles sharing a common sequence motif constitute the primary known genetic risk factor for rheumatoid arthritis. The influence of polymorphisms associated with differential cytokine expression on disease susceptibility is currently of much interest. Most attention has been focused on associations with susceptibility to benign immunologically-mediated diseases, including a number of gut diseases. However, recent work from our laboratory indicates that cytokine polymorphisms may influence susceptibility to and prognosis in a number of different cancers, including malignant melanoma skin cancer and solid tumours which may be influenced by diet, such as prostate cancer (collaboration with the CRC/BPG UK Familial Prostate Cancer study). In addition, preliminary work suggests that dietary modulation of expression levels of certain cytokines in healthy human subjects may be genotype dependent.
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PMID:Gene polymorphisms, inflammatory diseases and cancer. 1269 Nov 74

In reactive and postinfectious arthritis the joints are generally sterile but the presence of bacterial antigens and nucleic acids has been reported. To investigate whether organisms traffic to affected joints in these conditions, we performed reverse transcription PCR using universal primers to amplify any bacterial 16S rRNA sequences present in synovial fluid. Bacterial sequences were detected in most cases, even after treatment of the synovial fluid with DNase, implying the presence of bacterial RNA and therefore of transcriptionally active bacteria. Analysis of a large number of sequences revealed that, as reported in rheumatoid arthritis, most were derived from gut and skin commensals. Organisms known to have triggered arthritis in each case were not found by sequencing the products obtained using universal primers, but could in some cases be shown to be present by amplifying with species specific primers. This was the case for Yersinia pseudotuberculosis and Chlamydia trachomatis. However, in arthritis thought to be related to Campylobacter infection the sequences obtained were not from Campylobacter jejuni or C. coli, but from other Campylobacter spp. that are not known to be associated with reactive arthritis and are probably present as commensals in the gut. We conclude that although rRNA from reactive arthritis associated organisms can be detected in affected joints, bacterial RNA from many other bacteria is also present, as was previously noted in studies of other forms of inflammatory arthropathy.
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PMID:Investigation of infectious agents associated with arthritis by reverse transcription PCR of bacterial rRNA. 1271 47

Arthritis afflicts approximately 43 million Americans or approximately 16.6% of the US population. The two most common and best known types of arthritis are osteoarthritis (OA) and rheumatoid arthritis (RA). A significant amount of scientific research has been done in attempts to explain what initiates forms of arthritis, how it is promoted and perpetuated and how to effectively intervene in the disease process and promote cartilage remodeling. Current pharmacological strategies mainly address immune suppression and antiinflammatory mechanisms and have had limited success. Recent research provides evidence that alterations in the three-dimensional configuration of glycoproteins are responsible for the recognition/response signaling that catalyzes T-cell attack. Oral administration of autoantigens has been shown to suppress a variety of experimentally induced autoimmune pathologies, including antigen-induced RA. The interaction between gut-associated lymphoid tissue in the duodenum and epitopes of orally administered undenatured type II collagen facilitates oral tolerance to the antigen and stems systemic T-cell attack on joint cartilage. Previous studies have shown that small doses of orally administered undenatured type II chicken collagen effectively deactivate killer T-cell attack. A novel glycosylated undenatured type II collagen material (UC-II) was developed to preserve biological activity. The presence of active epitopes in the UC-II collagen is confirmed by an enzyme-linked immunosorbent assay test and distinguishes this form from hydrolyzed or denatured collagen. Oral intake of small amounts of glycosylated UC-II presents active epitopes, with the correct three-dimensional structures, to Peyer's patches, which influences the signaling required for the development of immune tolerance. UC-II has demonstrated the ability to induce tolerance, effectively reducing joint pain and swelling in RA subjects. A pilot study was conducted for 42 days to evaluate the efficacy of UC-II (10 mg/day) in five female subjects (58-78 years) suffering from significant joint pain. Significant pain reduction including morning stiffness, stiffness following periods of rest, pain that worsens with use of the affected joint and loss of joint range of motion and function was observed. Thus, UC-II may serve as a novel therapeutic tool in joint inflammatory conditions and symptoms of OA and RA.
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PMID:Effects of orally administered undenatured type II collagen against arthritic inflammatory diseases: a mechanistic exploration. 1283 47


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