The Main Challenges in Systemic Lupus Erythematosus: Where Do We Stand?

Piga, Matteo; Arnaud, Laurent

doi:10.3390/jcm10020243

Cited by 61 publications

(43 citation statements)

References 82 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Skin lesions are frequent, such as symmetric malar erythema, photo sensibility, hyperkeratosis, ecchymosis, oral or mucosal ulcerations, alopecia. Proteinuria or nephrotic syndrome, changes in urinary sediment, increase in serum creatinine and arterial hypertension are clinical manifestations of lupus nephritis [ 1 , 2 ]. SLE—Autoimmune prototype disease—is characterized by abnormal responses of T and B immune cells with excessive synthesis of autoantibodies and immune circulant complexes [ 3 ] associated with nonimmune factors [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Cellular Response against Oxidative Stress, a Novel Insight into Lupus Nephritis Pathogenesis

Ene

Georgescu

Tampa

et al. 2021

JPM

View full text Add to dashboard Cite

The interaction of reactive oxygen species (ROS) with lipids, proteins, nucleic acids and hydrocarbonates promotes acute and chronic tissue damage, mediates immunomodulation and triggers autoimmunity in systemic lupus erythematous (SLE) patients. The aim of the study was to determine the pathophysiological mechanisms of the oxidative stress-related damage and molecular mechanisms to counteract oxidative stimuli in lupus nephritis. Our study included 38 SLE patients with lupus nephritis (LN group), 44 SLE patients without renal impairment (non-LN group) and 40 healthy volunteers as control group. In the present paper, we evaluated serum lipid peroxidation, DNA oxidation, oxidized proteins, carbohydrate oxidation, and endogenous protective systems. We detected defective DNA repair mechanisms via 8-oxoguanine-DNA-glycosylase (OGG1), the reduced regulatory effect of soluble receptor for advanced glycation end products (sRAGE) in the activation of AGE-RAGE axis, low levels of thiols, disulphide bonds formation and high nitrotyrosination in lupus nephritis. All these data help us to identify more molecular mechanisms to counteract oxidative stress in LN that could permit a more precise assessment of disease prognosis, as well as developing new therapeutic targets.

show abstract

Section: Introductionmentioning

confidence: 99%

Cellular Response against Oxidative Stress, a Novel Insight into Lupus Nephritis Pathogenesis

Ene

Georgescu

Tampa

et al. 2021

JPM

View full text Add to dashboard Cite

show abstract

“…Systemic lupus erythematosus (SLE, ICD10 Code: M32.9) is an autoimmune disorder progressively resulting in multi-system organ damage (Piga and Arnaud, 2021). Compared with other rheumatic diseases, the irreversible multiorgan involvement and dysfunction of SLE lead to more life-threatening complications, including infections, renal failure, pulmonary arterial hypertension and cardio-cerebrovascular diseases (Mu et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Total Glucosides of Paeonia lactiflora for Safely Reducing Disease Activity in Systemic Lupus Erythematosus: A Systematic Review and Meta-Analysis

et al. 2022

View full text Add to dashboard Cite

Background: Total glucosides of paeony (TGP), extracted from the dried roots of Paeonia lactiflora Pall., are proven to regulate immune function in various rheumatic diseases. We aim to systematically evaluate the efficacy and safety of TGP in reducing disease activity in systemic lupus erythematosus (SLE).Methods: We searched trials in seven electronic databases and two clinical trail registries. Randomized controlled trials (RCTs) evaluating efficacy and safety of TGP for SLE were identified. The Cochrane Risk of Bias Tool 2.0 was used for quality assessment of the included trials, and RevMan 5.4 software was used for meta-analysis.Results: A total of 14 RCTs were included, including 978 participants, 492 in the intervention group and 486 in the control group. Regarding the efficacy of TGP for SLE, results showed that TGP plus conventional treatments (CTs) was superior to CTs alone in reducing disease activity (MDSLEDAI-1m = −3.54, 95% CI = −4.08 to −3.00, p < 0.00001; MDSLEDAI-2m = −3.80, 95% CI = −4.51 to −3.09, p < 0.00001; MDSLEDAI-3m = −1.62, 95% CI = −2.60 to −0.64, p < 0.0001; MDSLEDAI-6m = −1.97, 95% CI = −3.18 to −0.76, p = 0.001). The results also showed that TGP contributed to a betterment in improving other outcomes related to lupus activity, such as ESR, CRP, complement proteins (C3, C4), and immunoglobulins (IgA, IgM). In addition, TGP significantly decreased average daily glucocorticoid dosage and cumulative cyclophosamide dosage, as well as disease recurrence rate. In terms of safety, TGP may reduce the incidence of adverse reactions (RR = 0.51, 95% CI = 0.29 to 0.88, p = 0.01). The certainty of the evidence were assessed as moderate to low.Conclusion: TGP appears potentially effective and generally safe in reducing disease activity in SLE. However, in view of high risk of bias, the findings need to be confirmed in high-quality trials.Systematic Review Registration: https://www.crd.york.ac.uk/prospero, identifier CRD42021274850

show abstract

“…Despite advances in treatment strategies leading to an improved prognosis, several challenges and unmet needs remain for patients living with systemic lupus erythematosus (SLE) (1,2). In sharp contrast to other rheumatic diseases, treatment options in advanced SLE are limited.…”

Section: Introductionmentioning

confidence: 99%

Clinical Experience of Proteasome Inhibitor Bortezomib Regarding Efficacy and Safety in Severe Systemic Lupus Erythematosus: A Nationwide Study

Walhelm

Gunnarsson

Heijke³

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

As treatment options in advanced systematic lupus erythematosus (SLE) are limited, there is an urgent need for new and effective therapeutic alternatives for selected cases with severe disease. Bortezomib (BTZ) is a specific, reversible, inhibitor of the 20S subunit of the proteasome. Herein, we report clinical experience regarding efficacy and safety from all patients receiving BTZ as therapy for SLE in Sweden during the years 2014−2020. 8 females and 4 males were included with a mean disease duration at BTZ initiation of 8.8 years (range 0.7–20 years). Renal involvement was the main target for BTZ. Reduction of global disease activity was recorded by decreasing SLEDAI-2K scores over time and remained significantly reduced at the 6-month (p=0.007) and the 12-month (p=0.008) follow-up visits. From BTZ initiation, complement protein 3 (C3) levels increased significantly after the 2nd treatment cycle (p=0.05), the 6-month (p=0.03) and the 12-month (p=0.04) follow-up visits. The urine albumin/creatinine ratio declined over time and reached significance at the 6-month (p=0.008) and the 12-month follow-up visits (p=0.004). Seroconversion of anti-dsDNA (27%), anti-C1q (50%) and anti-Sm (67%) was observed. 6 of 12 patients experienced at least one side-effect during follow-up, whereof the most common adverse events were infections. Safety parameters (C-reactive protein, blood cell counts) mainly remained stable over time. To conclude, we report favorable therapeutic effects of BTZ used in combination with corticosteroids in a majority of patients with severe SLE manifestations irresponsive to conventional immunosuppressive agents. Reduction of proteinuria was observed over time as well as seroconversion of some autoantibody specificities. In most patients, tolerance was acceptable but mild adverse events was not uncommon. Special attention should be paid to infections and hypogammaglobinemia.

show abstract

The Main Challenges in Systemic Lupus Erythematosus: Where Do We Stand?

Cited by 61 publications

References 82 publications

Cellular Response against Oxidative Stress, a Novel Insight into Lupus Nephritis Pathogenesis

Cellular Response against Oxidative Stress, a Novel Insight into Lupus Nephritis Pathogenesis

Total Glucosides of Paeonia lactiflora for Safely Reducing Disease Activity in Systemic Lupus Erythematosus: A Systematic Review and Meta-Analysis

Clinical Experience of Proteasome Inhibitor Bortezomib Regarding Efficacy and Safety in Severe Systemic Lupus Erythematosus: A Nationwide Study

Contact Info

Product

Resources

About