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)

Modulation of the T-cell response depends chiefly on regulatory T cells (Treg), which express CD4 and CD25. Some Treg cells are present naturally, whereas others are induced in response to antigens. The immunomodulating effects of Treg cells are mediated by membrane molecules (e.g., CTLA4, GITR, and OX40) and cytokines. IL-35 seems to be a crucial mediator, although IL-10 and TGFbeta are also important. The role for Treg cells in rheumatoid arthritis (RA) has been established in both patients and animal models. Treg function is deficient in RA, whereas Treg counts vary. Treg counts increase in patients who are responding to TNFalpha antagonist therapy. Among current hypotheses, Treg expansion or transfer may hold promise for the treatment of RA.
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PMID:Regulatory T cells (Treg) in rheumatoid arthritis. 1902 28

Rheumatoid arthritis is a chronic systemic inflammatory disease with major articular manifestations. While its aetiology still remains to be resolved, our understanding on the pathogenesis of rheumatoid arthritis has become clearer during two decades enlightening the role of adaptative immunity in the development of the symptoms and signs as well as in the progression of the pathological articular changes taking place in inadequately controlled disease. T lymphocytes are considered to be an important cell type in the pathogenesis of rheumatoid arthritis through production of proinflammatory cytokines, promotion of formation of ectopic lymphoid structures and neovascularization in synovial tissue, promotion autoantibody production by B cells, and activation of synoviocytes and osteoclasts. Abatacept, a CTLA4-Ig fusion protein, represents a new therapeutic approach in rheumatoid arthritis. Abatacept attenuates T cell activation as it regulates the activation of T cells by inhibiting the CD80/86:CD28 co-stimulatory pathway that is required for the proper T cell activation. This MiniReview gives an overview on the mechanism of action of abatacept and summarizes the published clinical data on abatacept in the treatment of rheumatoid arthritis.
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PMID:Abatacept, a novel CD80/86-CD28 T cell co-stimulation modulator, in the treatment of rheumatoid arthritis. 1922 44

Rheumatoid arthritis is a chronic inflammatory polyarthritis and is thought to be an autoimmune, multifactorial and polygenic disease. Recent studies have uncovered many important players in the pathogenesis of rheumatoid arthritis. Immune cells, mesenchymal cells, and bone-associated cells are all involved in the pathogenesis and are closely related with each other. The genetic predisposition to rheumatoid arthritis is confirmed by many family studies and HLA association studies. Genome-wide disease association studies identified genetic risk foci, such as HLA-DRB1, PADI4, and PTPN22. In addition to the genetic contribution, environmental factors are increasingly recognized. Many studies revealed that smoking is a risk factor for rheumatoid arthritis. The role of B and T lymphocytes in the pathogenesis has been reevaluated by biological agents such as rituximab (anti-CD20 antibody) and abatacept (CTLA4-Ig) , respectively. T cells in rheumatoid arthritis have been shown to have the altered level of surface molecules such as CD28, cytokine pattern shift, and shortened telomere lengths. Moreover, telomere loss is recognized not only in lymphocytes but also in hematopoietic progenitor cells. This phenomenon and the presence of rheumatoid-specific anti-citrullinated protein antibodies are reported to be associated with HLA haplotypes.
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PMID:[Recent advances in the pathogenesis of rheumatoid arthritis]. 1925 39

There are two types of biological agents for the treatment of rheumatoid arthritis (RA); monoclonal antibodies and recombinant proteins. Among the latter, etanercept, a recombinant fusion protein of soluble TNF receptor and IgG was approved in 2005 in Japan. The post-marketing surveillance of 13,894 RA patients revealed the efficacy and safety profiles of etanercept in the Japanese population, as well as overseas studies. Abatacept, a recombinant fusion protein of CTLA4 and IgG, is another biological agent for RA. Two clinical trials disclosed the efficacy of abatacept for difficult-to-treat patients: the AIM for MTX-resistant cases and the ATTAIN for patients who are resistant to anti-TNF. The ATTEST trial suggested abatacept might have more acceptable safety profile than infliximab. These biologics are also promising for the treatment of RA for not only relieving clinical symptoms and signs but retarding structural damage.
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PMID:[Biological agents]. 1928 Sep 38

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease that causes significant morbidity and mortality. RA patients should be started with DMARD represented by methotrexate (MTX) as early as possible. However, even use of MTX often fails to control disease activity and to prevent structural damage and, thereby, more effective treatment strategies are needed. Since TNF-alpha and IL-6 play a pivotal role in the pathological processes of RA, biologics targeting these cytokines with MTX, have revolutionized the treatment of RA, producing significant improvement in clinical, radiographic and functional outcomes not seen previously. However, even with these drugs the frequency and degree of responses are restricted. Therefore, new agents targeting cell surface molecules which are involved in cellular interaction and/or signaling on immune cells have been emerging, in order to increase response rates and to achieve high frequencies of remission or even cure. Two biologics abatacept, a CTLA4-Ig fusion protein, and rituximab, an anti-CD20 antibody, were launched in US and EU for the treatment of RA and many biologics are under the clinical trials from the similar concept. Thus, certain biologics have brought about paradigm shift in the treatment of rheumatic diseases, but an economical issue remains unsolved. In order to overcome the concern, low molecular weight chemical products have been rethought. Not a few agents targeting intracellular activation signaling in immune cells such as Jak and Syk are under clinical examinations and some of them appear to show wonderful results, which are comparable to biologics in the context of the treatment of rheumatic diseases. The prospects are here.
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PMID:[Recent progress in clinical trials for rheumatic diseases]. 1928 Sep 42

Talk of numerous genetic risk factors for rheumatoid arthritis (RA) and psoriasis has been percolating for years, but with the exception of the human leukocyte antigen (HLA) region, none have been definitively identified. Recently the results of multiple, well powered, genetic case-control studies have begun to appear providing convincing statistical evidence for at least ten non-HLA related risk genes or loci (C5/TRAF1, CD40, CTLA4, KIF5A/PIP4K2C, MMEL1/TNFRSF14, PADI4, PRKCQ, PTPN22, STAT4, and TNFAIP3/OLIG3) for RA and six (IL12B, IL13, IL23R, STAT2/IL23A, TNFAIP3, and TNIP1) for psoriasis. These initial, novel findings are beginning to shed light on the molecular pathways pertinent to the individual diseases and highlight the pleiotropic effects of several risk factors as well as the allelic heterogeneity underlying susceptibility to these and other autoimmune diseases.
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PMID:Unraveling the genetics of complex diseases: susceptibility genes for rheumatoid arthritis and psoriasis. 1944 72

We conducted a genome-wide association study of rheumatoid arthritis in 2,418 cases and 4,504 controls from North America and identified an association at the REL locus, encoding c-Rel, on chromosome 2p13 (rs13031237, P = 6.01 x 10(-10)). Replication in independent case-control datasets comprising 2,604 cases and 2,882 controls confirmed this association, yielding an allelic OR = 1.25 (P = 3.08 x 10(-14)) for marker rs13031237 and an allelic OR = 1.21 (P = 2.60 x 10(-11)) for marker rs13017599 in the combined dataset. The combined dataset also provides definitive support for associations at both CTLA4 (rs231735; OR = 0.85; P = 6.25 x 10(-9)) and BLK (rs2736340; OR = 1.19; P = 5.69 x 10(-9)). c-Rel is an NF-kappaB family member with distinct functional properties in hematopoietic cells, and its association with rheumatoid arthritis suggests disease pathways that involve other recently identified rheumatoid arthritis susceptibility genes including CD40, TRAF1, TNFAIP3 and PRKCQ.
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PMID:REL, encoding a member of the NF-kappaB family of transcription factors, is a newly defined risk locus for rheumatoid arthritis. 1950 88

Most of autoimmune and collagen diseases such as rheumatoid arthritis and systemic lupus erythematosus are multifactorial diseases, where both genetic and environmental factors are involved in their pathogenesis. Recent progress in the genetic study of disease has enabled us to perform genome-wide scanning of disease susceptibility genes and brought us a new picture of disease mechanism. We herein review the recent findings of genetic studies on autoimmune and collagen diseases. Some of disease-susceptibility genes like PTPN22 and CTLA4 are shared in common among different diseases, while other genes contribute to a specific disease, suggesting combination of genetic predispositions may determine an individual's pathophysiology.
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PMID:[Genetics of autoimmune and collagen diseases]. 1950

Both genetic and environmental factors affect susceptibility, severity and probably drugs' efficacy in patients with rheumatoid arthritis (RA). After initial completion of the Human Genome Project on the 16th February 2001, significant progress has been made in identifying other than HLA genome regions linked to the increased RA susceptibility. As an effect several new genes have been recognized as an HLA-independent genetic risk factors of RA. PTPN22 gene polymorphism, C5/TRAF1 genes region polymorphism and TNFAIP3-OLIG3 genes region polymorphism(s) are among newly identified and already confirmed genetic risk factors, whereas STAT 4, CTLA4, PADI4 and IRF5 genes polymorphisms are listed among probable RA development genetic risk factors.
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PMID:[Influence of genetic factors on development and severity of rheumatoid arthritis--part I]. 1985 86

To explore the role of proline-rich tyrosine kinase 2 (PYK2) in systemic lupus erythematosus (SLE), we studied the expression, activation, and function of PYK2 in peripheral blood mononuclear cells (PBMC) from 36 SLE patients. As controls, samples from 19 patients with rheumatoid arthritis and 15 healthy individuals were studied simultaneously. We found a significant increase of both the total PYK2 protein and its activated/phosphorylated form in PBMCs from patients with SLE, particularly those with the complication of nephritis (WHO class IV). There is a clear correlation between the activation of PYK2 and the level of serum complements. In active SLE patients, activation of PYK2 in PBMCs accompanies the increased cell proliferation and the induced expression of co-stimulatory molecules CD40L and CTLA4. These results indicate that phosphorylated PYK2 may induce the expression of CD40L and CTLA4, and subsequently the cell proliferation. PYK2 signaling enhances the autoreactive lymphocyte activation and plays an important role in the pathogenesis of SLE.
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PMID:Activation signal transduction by proline-rich tyrosine kinase 2 (PYK2) in peripheral blood mononuclear cells from patients with systemic lupus erythematosus. 1985 14


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