Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pure red cell aplasia (PRCA) is a syndrome defined by a normocytic normochromic anemia with severe reticulocytopenia and marked reduction or absence of erythroid precursors from the bone marrow. Diamond-Blackfan anemia is a congenital form of PRCA. Acquired PRCA may be either a primary disorder or secondary to some other disorder or agent. Primary acquired PRCA is an autoimmune disorder that is frequently antibody-mediated. Myelodysplastic syndromes may also present with the morphologic appearance of PRCA. Secondary acquired PRCA may be associated with collagen vascular/autoimmune disorders such as systemic lupus erythematosus; lymphoproliferative disorders such as chronic lymphocytic leukemia or large granular lymphocyte leukemia; infections, particularly B19 parvovirus; thymoma and other solid tumors; or a variety of other disorders, drugs, or toxic agents. The therapeutic approach to PRCA typically involves immunosuppression, but specific pathogenic subtypes are associated with specific therapeutic approaches. Cyclosporine A, with or without concurrent corticosteroids, appears to be the single most effective immunosuppressive agent.
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PMID:Pure red cell aplasia. 2788 71

Pure red cell aplasia (PRCA) is a syndrome defined by a normocytic normochromic anemia with severe reticulocytopenia and marked reduction or absence of erythroid precursors from the bone marrow. Diamond-Blackfan anemia is a congenital form of PRCA. Acquired PRCA may be either a primary disorder or secondary to some other disorder or agent. Primary acquired PRCA is an autoimmune disorder that is frequently antibody-mediated. Myelodysplastic syndromes may also present with the morphologic appearance of PRCA. Secondary acquired PRCA may be associated with collagen vascular/autoimmune disorders such as systemic lupus erythematosus; lymphoproliferative disorders such as chronic lymphocytic leukemia or large granular lymphocyte leukemia; infections, particularly B19 parvovirus; thymoma and other solid tumors; or a variety of other disorders, drugs, or toxic agents. The therapeutic approach to PRCA typically involves immunosuppression, but specific pathogenic subtypes are associated with specific therapeutic approaches. Cyclosporine A, with or without concurrent corticosteroids, appears to be the single most effective immunosuppressive agent.
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PMID:Pure red cell aplasia. 2791 62

Circulating autoantibodies and immune complex deposition are pathological hallmarks of systemic lupus erythematosus (SLE). B cell differentiation into plasma cells (PCs) and some T cell subsets that function as B cell helpers can be therapeutic targets of SLE. Mechanistic target of rapamycin (mTOR) signaling is implicated in the formation of B cells and germinal centers (GCs). We assessed the effect of metformin, which inhibits mTOR, on the development of autoimmunity using Roquinsan/san mice. Oral administration of metformin inhibited the formation of splenic follicles and inflammation in kidney and liver tissues. It also decreased serum levels of anti-dsDNA Abs without affecting serum glucose levels. Moreover, metformin inhibited CD21highCD23low marginal zone B cells, B220+GL7+ GC B cells, B220-CD138+ PCs, and GC formation. A significant reduction in ICOS+ follicular helper T cells was found in the spleens of the metformin-treated group compared with the vehicle-treated group. In addition, metformin inhibited Th17 cells and induced regulatory T cells. These alterations in B and T cell subsets by metformin were associated with enhanced AMPK expression and inhibition of mTOR-STAT3 signaling. Furthermore, metformin induced p53 and NF erythroid-2-related factor-2 activity in splenic CD4+ T cells. Taken together, metformin-induced alterations in AMPK-mTOR-STAT3 signaling may have therapeutic value in SLE by inhibiting B cell differentiation into PCs and GCs.
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PMID:Metformin Suppresses Systemic Autoimmunity in Roquinsan/san Mice through Inhibiting B Cell Differentiation into Plasma Cells via Regulation of AMPK/mTOR/STAT3. 2824 51

Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a master regulator of cellular protective processes. Rheumatic diseases are chronic conditions characterized by inflammation, pain, tissue damage and limitations in function. Main examples are rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis and osteoporosis. Their high prevalence constitutes a major health problem with an important social and economic impact. A wide range of evidence indicates that Nrf2 may control different mechanisms involved in the physiopathology of rheumatic conditions. Therefore, the appropriate expression and balance of Nrf2 is necessary for regulation of oxidative stress, inflammation, immune responses, and cartilage and bone metabolism. Numerous studies have demonstrated that Nrf2 deficiency aggravates the disease in experimental models while Nrf2 activation results in immunoregulatory and anti-inflammatory effects. These reports reinforce the increasing interest in the pharmacologic regulation of Nrf2 and its potential applications. Nevertheless, a majority of Nrf2 inducers are electrophilic molecules which may present off-target effects. In recent years, novel strategies have been sought to modulate the Nrf2 pathway which has emerged as a therapeutic target in rheumatic conditions.
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PMID:Nrf2 as a therapeutic target for rheumatic diseases. 2966 Mar 14

Systemic lupus erythematosus (SLE) is an autoimmune disorder associated with inflammation and multiple organ involvement. Individually, dendritic cells (DCs) and oxidative stress have been well discussed for their critical involvement in the pathogenesis of disease but the precise impact of oxidative stress on DCs in relation to SLE disease activity is yet to be scrutinized. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1) pathway is the cellular mechanism to combat increased reactive oxygen species (ROS). The current study was framed in order to understand redox regulation in DCs along with an argument in context to disease activity. Here, 23 SLE patients along with 10 healthy controls were enrolled and disease activity was calculated as the recent change in SLEDAI score. We found the percentage of circulating plasmacytoid DCs (pDCs) was increased with an increase in disease activity. Altered DCs functionality along with disease activity was further supported with the differential concentration of Type I IFNs. The disease activity was positively associated with increased levels of ROS. A relevant reason for increased ROS was further explained with the decreased levels of transcription factor Nrf2. Hence, the present study suggests that SLE specific DCs displayed elevation in ROS and this outcome might be due to impaired free radical clearance by Nrf2. Correlation studies further established an association of disease activity with increased ROS, Type I IFNs levels and decreased activity of oxidative stress regulating enzymes.
Lupus 2020 Oct
PMID:Altered redox regulation by Nrf2-Keap1 system in dendritic cells of systemic lupus erythematosus patients. 3281 Dec 77

Research on the antioxidant pathway comprising the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) and its cytoplasmic inhibitor Kelch-like ECH-associated protein 1 (Keap1) is ever increasing. As modulators of this pathway have started to be used in clinical trials and clinical practice, Nrf2 has become the subject of several patents. To assess the patent landscape of the last three years on Nrf2 and evaluate the main fields they refer to, we used the web-based tool PatSeer Pro to identify patents mentioning the Nrf2 pathway between January 2017 and May 2020. This search resulted in 509 unique patents that focus on topics such as autoimmune, neurodegenerative, liver, kidney, and lung diseases and refer to modulators (mainly activators) of the Nrf2 pathway as potential treatments. Autoimmunity emerged as the main theme among the topics of Nrf2 patents, including a broad range of diseases, such as systemic sclerosis, systemic lupus erythematosus, multiple sclerosis, inflammatory bowel diseases, Hashimoto's thyroiditis, etc.; however, there was a dearth of experimental support for the respective patents' claims. Given that chronic inflammation is the main element of the pathophysiology of most autoimmune diseases, the majority of patents referring to activation of Nrf2 as a method to treat autoimmune diseases base their claims on the well-established anti-inflammatory role of Nrf2. In conclusion, there is strong interest in securing intellectual property rights relating to the potential use of Nrf2 pathway activators in a variety of diseases, and this trend parallels the rise in related research publications. However, in the case of autoimmunity, more research is warranted to support the potential beneficial effects of Nrf2 modulation in each disease.
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PMID:Patent Review (2017-2020) of the Keap1/Nrf2 Pathway Using PatSeer Pro: Focus on Autoimmune Diseases. 3321 84


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