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

T lymphocyte activation is associated with nitric oxide (NO) production, which plays an essential role in multiple T cell functions. NO acts as a messenger, activating soluble guanyl cyclase and participating in the transduction signaling pathways involving cyclic GMP. NO modulates mitochondrial events that are involved in apoptosis and regulates mitochondrial membrane potential and mitochondrial biogenesis in many cell types, including lymphocytes. Mitochondrial hyperpolarization (MHP), an early and reversible event during both activation and apoptosis of Tlymphocytes, is regulated by NO. Here, we discuss recent evidence that NO-induced MHP represents a molecular switch in multiple T cell signaling pathways. Overproduction of NO in systemic lupus erythematosus induces mitochondrial biogenesis and alters Ca(2+) signaling. Thus, whereas NO plays a physiological role in lymphocyte cell signaling, its overproduction may disturb normal T cell function, contributing to the pathogenesis of autoimmunity.
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PMID:Nitric oxide, mitochondrial hyperpolarization, and T cell activation. 1746 31

Whilst many physiological functions of nitric oxide (NO) have been revealed so far, recent evidence proposes an essential role for NO in T lymphocyte activation and signal transduction. NO acts as a second messenger, activating soluble guanyl cyclase and participating in signal transduction pathways involving cyclic GMP. NO modulates mitochondrial events that are involved in apoptosis and regulates mitochondrial biogenesis in many cell types, including lymphocytes. Several studies undertaken on patients with RA and SLE have documented increased endogenous NO synthesis, although the effects of NO may be distinct. Here, we discuss recent evidence that NO contributes to T cell dysfunction in both SLE and RA by altering multiple signaling pathways in T cells. Although NO may play a physiological role in lymphocyte cell signaling, its overproduction may perturb T cell activation, differentiation and effector responses, each of which may contribute in different ways to the pathogenesis of autoimmunity.
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PMID:Nitric oxide, chronic inflammation and autoimmunity. 1756 90

We report the case of a 40-year-old patient with systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) overlap syndrome with pulmonary arterial hypertension (overlap-PAH) that was successfully treated with a combination of immunosuppressive therapy and the soluble guanylate cyclase stimulator riociguat. She was diagnosed with mixed connective tissue disease (MCTD) two years prior to admission. She was admitted to our hospital with dyspnea on exertion and progressive skin sclerosis. She fulfilled both SLE and SSc classification criteria and was re-diagnosed with overlap syndrome. The tricuspid valve pressure gradient (TRPG) on echocardiography was 64 mmHg at admission. On right heart catheterization, mean pulmonary arterial pressure (mPAP) was 43 mmHg and pulmonary capillary wedge pressure was 15 mmHg. We diagnosed her with SSc-SLE overlap-PAH and started treatment with corticosteroids and intravenous cyclophosphamide. We also started treatment with riociguat because we speculated she had a component of SSc-PAH and that immunosuppressive therapy alone may be insufficient. We chose riociguat because of its favorable treatment effect on SSc-PAH. Two months after treatment, her TRPG improved to 33 mmHg and the skin sclerosis improved dramatically, suggesting the efficacy of multi-drug treatment and the importance of early intervention.
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PMID:Systemic Sclerosis and Systemic Lupus Erythematosus Overlap Syndrome with Pulmonary Arterial Hypertension Successfully Treated with Immunosuppressive Therapy and Riociguat. 3118 6

Pulmonary hypertension (PH) can develop in different systemic autoimmune rheumatic diseases (SARD), such as systemic scleroderma (SSD), systemic lupus erythematosus, rheumatoid arthritis, and mixed connective tissue disease In most cases, patients with SARD develop WHO group I PH (pulmonary arterial hypertension associated with systemic connective tissue diseases, PAH-SCTD). General prevalence of this pathology reaches 15 cases per million adults. Most cases of PAH-SCTD are induced by SSD. Survival of PAH-SCTD patients is generally lower than survival of patients with other forms of LAH. Treatment of any SARD, including in LAH, implies a complex approach using glucocorticoids, disease-modifying anti-rheumatic drugs (cyclophosphamide, methotrexate, azathioprine, and others), and genetically engineered biologics. Specific targeted therapy is indicated for most patients with PAH-SCTD. The representative of a new class (soluble guanylate cyclase (sGC) stimulators), riociguat, has been approved for the treatment of PAH. This drug has a unique double mechanism of action: (i) sGC sensibilization to endogenous nitric oxide (NO) by stabilizing the NO-sGC bond; and (ii) direct, NO-independent sGC stimulation. For patients with PAH-SCTD, riociguat is the major alternative to phosphodiesterase-5 inhibitors both as monotherapy and combination therapy.
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PMID:[The place of riociguat in the treatment of patients with pulmonary arterial hypertension associated with systemic connective tissue diseases]. 3313 80