Dan Luo; Jun Li; Manli Hu; You Wang; Pei Pi; Min Ning; Jun Wu
Abstract
Background: Lupus nephritis (LN) refers to the injury caused by systemic lupus erythematosus (SLE) involving the kidneys. A previous study identified angiopoietin-like protein 4 (ANGPTL4) as a novel urinary biomarker for tracking disease activity in LN.Objective: To investigate the detailed role and ...
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Background: Lupus nephritis (LN) refers to the injury caused by systemic lupus erythematosus (SLE) involving the kidneys. A previous study identified angiopoietin-like protein 4 (ANGPTL4) as a novel urinary biomarker for tracking disease activity in LN.Objective: To investigate the detailed role and regulatory mechanism of ANGPTL4 in experimental models of LN.Methods: MRL/lpr mice 11-week-old were injected with adeno-associated virus (AAV)-mediated ANGPTL4 short hairpin RNA (shRNA). At 16 and 20 weeks of age, 24-h urine samples were harvested to measure proteinuria levels. After the mice were sacrificed, blood and kidney tissues were harvested to examine serum creatinine (cr) and blood urea nitrogen (BUN) levels, kidney histological changes, and pro-inflammatory cytokine production. Additionally, the levels of NLRP3 inflammasome-associated molecules in mouse renal tissues were detected to clarify the underlying mechanism.Results: The AAV-sh-ANGPTL4 injection significantly reduced the proteinuria, cr, and BUN levels in MRL/lpr mice. ANGPTL4 silencing ameliorated glomerular, tubular, and interstitial damage in mice, mitigating the pathological alternations of LN. In addition, ANGPTL4 knockdown repressed pro-inflammatory cytokine production in the kidneys. Mechanically, ANGPTL4 suppression inhibited NLRP3 inflammasome expression in renal tissues of mice.Conclusion: ANGPTL4 silencing inhibits the NLRP3 inflammasome-mediated inflammatory response, thereby ameliorating LN in MRL/lpr mice.
Qiaoying Jiang; Caixia Qi; Liwei Yang
Abstract
Background: Systemic lupus erythematosus (SLE) is most likely to occur during the first and second trimesters of pregnancy. There were few studies focused on the new-onset SLE during the late pregnancy or puerperium. SLE has been considered an important cause of thrombocytopenia. However, lymphoma may ...
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Background: Systemic lupus erythematosus (SLE) is most likely to occur during the first and second trimesters of pregnancy. There were few studies focused on the new-onset SLE during the late pregnancy or puerperium. SLE has been considered an important cause of thrombocytopenia. However, lymphoma may also be a cause of thrombocytopenia. Here, we reported a challenging case of new-onset SLE occurred at the gestational age of 33 weeks, and the pregnant woman suffered lymphoma before. Case presentation: A 25-year-old primigravid Chinese woman with a medical history of non-Hodgkin lymphoma (NHL) suffered thrombocytopenia at 30+5 weeks of gestation. Her skin rashes occurred one week later. Her platelet count was decreased progressively. She had been misdiagnosed with the recrudescence of NHL. The final diagnosis of new-onset SLE was confirmed and a cesarean section was performed at the 34th week of pregnancy. Both the pregnant woman and the newborn were cured with good prognosis. Conclusion: SLE should be considered in a pregnant woman with a medical history of malignancy to rule out other diseases, especially the rheumatic immune diseases.
Dijiao Tang; Qi Tang; Long Zhang; Hongxu Wang
Abstract
Background: Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematosus (SLE).The neutrophil to lymphocyte ratio (NLR) is a promising predictor and prognostic factor. An increased NLR is associated with a poor prognosis of several inflammatory diseases. Objective: ...
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Background: Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematosus (SLE).The neutrophil to lymphocyte ratio (NLR) is a promising predictor and prognostic factor. An increased NLR is associated with a poor prognosis of several inflammatory diseases. Objective: To evaluate the value of NLR in the diagnosis and pre-assessment of the disease severity of LN. Methods: This retrospective study included 88 patients with LN, 51 SLE patients without kidney involvement, 79 patients with primary chronic nephritis (CN), and 52 healthy controls (HC). The differences among these four groups and diagnostic value of NLR for patients with LN were evaluated. Results: The NLR of patients with LN before treatment was significantly higher than that of the other three groups. NLR positively correlated with C-reactive protein (CRP), complement 3(C3), C4, and serum creatinine (SCr) (CRP: r=0.337, p=0.007; C3: r=0.222, p=0.042; C4: r=0.230, p=0.035; SCr: r=0.408, p <0.0001) but negatively correlated with total serum IgG (r=-0.226, p=0.041). The level of NLR increased with the severity of renal dysfunction NLR (area under the curve: 0.785, 95% CI: 0.708-0.862) was useful for the diagnosis of LN, and its optimal cut-off value was 5.44 (sensitivity: 65.9%, specificity: 86.3%). Conclusions: NLR would be useful for the diagnosis of LN and reflects the severity of renal dysfunction Therefore, evaluating NLR before treatment could help clinicians to identify potential renal involvement in patients with SLE and distinguish LN from CN.
Yousef Khanjari; Morteza Oladnabi; Nafiseh Abdollahi; Ahmad Heidari; Saeed Mohammadi; Alijan Tabarraei
Abstract
Background: Programmed cell death protein 1 (PD-1) is a negative costimulatory molecule with immunomodulatory properties. Recently, PD-1 gene defects have attracted attention in the pathogenesis of SLE. Objective: Here, we assessed the association of PD-1 gene polymorphisms in intron 4 and haplotypes ...
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Background: Programmed cell death protein 1 (PD-1) is a negative costimulatory molecule with immunomodulatory properties. Recently, PD-1 gene defects have attracted attention in the pathogenesis of SLE. Objective: Here, we assessed the association of PD-1 gene polymorphisms in intron 4 and haplotypes with the susceptibility to SLE. Method: Seventy-six SLE patients and 159 healthy controls were included. We screened the polymorphisms by amplifying the intron 4 of the PD-1 gene with the specific primers followed by sequencing. Results: Two distinct SNPs were identified (rs6705653 and rs41386439) within the intron 4 of the PD-1 gene. The AA genotype of +7499 (G/A) SNP was associated with the higher risk of SLE [OR=3.31, 95% CI (1.25-8.76), p-value=0.045], while A allele was identified as a risk allele [OR=1.75, 95% CI (1.10-2.76), p-value=0.015]. However, no significant association was observed between the allele and the genotype frequencies of +7209 (C/T) polymorphic region of the PD-1 gene and susceptibility to SLE. Haplotype analysis showed the significantly higher presence of H2 haplotype (AC; +7499/+7209) [OR=1.70, 95% CI (1.24-2.33), p-value=0.0012] in SLE patients. Conclusion: To the best of our knowledge, this is the first report of the significant association of PD-1 +7499 (G/A) SNP with the SLE susceptibility and the first detection of both polymorphic loci in a population from Iran. However, more investigations are necessary to confirm these findings.
Jian-Ping Xiao; Xue-Rong Wang; Sen Zhang; Jun Wang; Chao Zhang; De-Guang Wang
Hadi Reihani; Maryam Rastin; Mahmoud Mahmoudi; Mohsen Ghoryani; Nafiseh Abdollahi; Nafiseh Sadat Tabasi; Shahrzad Zamani Taghizadeh Rabe; Maryam Sahebari
Volume 12, Issue 2 , June 2015, , Pages 82-93
Abstract
Background: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease. Emerging data suggests that T helper 17 (Th17) cells play a pathogenic role in SLE and the increased number of these cells correlates with disease activity. In recent years, 1α, 25-dihydroxyvitamin D3 (1,25VitD3) ...
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Background: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease. Emerging data suggests that T helper 17 (Th17) cells play a pathogenic role in SLE and the increased number of these cells correlates with disease activity. In recent years, 1α, 25-dihydroxyvitamin D3 (1,25VitD3) has been considered as an immunomodulatory factor. Objective: To investigate the effect of 1,25VitD3 on Th17 cells and on the expression of related cytokines in SLE patients. Method: Thirty SLE patients (newly diagnosed or in remission) were sampled for 10 ml whole blood to isolate peripheral blood mononuclear cells (PBMCs) using Ficoll-Hypaque density gradient centrifugation. Isolated cells were cultured in the presence and absence of 50 nM 1,25VitD3. After incubation, cells were harvested and stimulated for 4-5 hours with phorbol myristate acetate (PMA) and ionomycin in the presence of brefeldin A. IL-17 secreting cells were analyzed by flowcytometry. RNA was extracted from cultured cells, cDNA was synthesized, and the expression levels of IL-6, IL-17, IL-23 and TGF- β genes were assessed by real-time PCR. Results: The percentage of Th17 cells (CD3+ CD8- IL-17+ T cells) decreased significantly in 1,25VitD3-treated cells (3.67 ± 2.43%) compared to untreated cells (4.65 ± 2.75%) ( p=0.003). The expression of TGF- β up regulated (1.38-fold) and the expression of IL-6 (50%), IL-17 (27%) and IL-23 (64%) down regulated after 1,25VitD3 treatment. Conclusion: This study showed that 1,25VitD3 modulates Th17 related pathways in SLE patients and revealed the immunomodulatory effect of 1,25VitD3 on the Th17 mediated autoimmunity.
Sara Kashef; Reza Amin; Maryam Ayatollahi; Abbas Ghaderi
Volume 1, Issue 2 , September 2004, , Pages 117-123
Abstract
Background: Antiphospholipid antibody syndrome (APS) can either occur as a primary syndrome or associated with other autoimmune diseases such as systemic lupus erythematosus (SLE). Anticardiolipin antibody (aCL) of IgG and/or IgM isotype in blood, measured by a standardized ELISA is the most acceptable ...
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Background: Antiphospholipid antibody syndrome (APS) can either occur as a primary syndrome or associated with other autoimmune diseases such as systemic lupus erythematosus (SLE). Anticardiolipin antibody (aCL) of IgG and/or IgM isotype in blood, measured by a standardized ELISA is the most acceptable laboratory criteria. APS IgG isotype, particularly IgG2 subclass is more strongly associated with thrombosis. Objectives: This study was done to determine the prevalence of IgG aCL and its subclasses in relation to APS symptoms, in a group of juvenile rheumatoid arthritis (JRA) and juvenile systemic lupus erythematosus (SLE) patients. Methods: In this prospective study, 28 JRA and 16 SLE patients, aged 3-18 years, were enrolled. IgG aCL was assayed by standard aCL ELISA. IgG subclasses were also assayed by ELISA on sera with medium to high titers of aCL. ACL assay was performed on at least two occasions for each patient, over 3-6 months period of follow up. Results: 29% (8/28) of JRA patients and 44% (7/16) of SLE patients had aCL. Six of SLE patients displayed APS related manifestations: hemolytic anemia, thrombocytopenia, arterial occlusion, valvular heart disease, livedo reticularis and pulmonary hypertension, but none of them had persistant medium or high titer of aCL. The lack of association of high titer of aCL with APS related symptoms was observed in two patients. The IgG subclasses were primarily IgG1 and IgG3. Conclusion: The prevalence of IgG aCL in this group of pediatric SLE and JRA is not uncommon but it’s relation to clinical manifestations is not clear. IgG1 and IgG3 subclasses were not associated with thrombosis, which is in agreement with previous studies.