BACKGROUND In this study,we retrospectively analysed macrophage infiltration and podocyte injury in three patients with diffuse proliferative lupus nephritis(LN)who un-derwent repeated renal biopsy.CASE SUMMARY Clinic...BACKGROUND In this study,we retrospectively analysed macrophage infiltration and podocyte injury in three patients with diffuse proliferative lupus nephritis(LN)who un-derwent repeated renal biopsy.CASE SUMMARY Clinical data of three diffuse proliferative LN patients with different pathological characteristics(case 1 was LN IV-G(A),case 2 was LN IV-G(A)+V,and case 3 was LN IV-G(A)+thrombotic microangiopathy)were reviewed.All patients underwent repeated renal biopsies 6 mo later,and renal biopsy specimens were studied.Macrophage infiltration was assessed by CD68 expression detected by immunohistochemical staining,and an immunofluorescence assay was used to detect podocin expression to assess podocyte damage.After treatment,Case 1 changed to LN III-(A),Case 2 remained as type V LN lesions,and Case 3,which changed to LN IV-S(A),had the worst prognosis.We observed reduced macro-phage infiltration after therapy.However,two of the patients with active lesions after treatment still showed macrophage infiltration in the renal interstitium.Before treatment,the three patients showed discontinuous expression of podocin.Notably,the integrity of podocin was restored after treatment in Case 1.CONCLUSION It may be possible to reverse podocyte damage and decrease the infiltrating ma-crophages in LN patients through effective treatment.展开更多
Membranous lupus nephritis(MLN),class V,is a distinct LN characterized by immune complex deposition on subepithelial kidney biopsy.MLN is often associated with nephrotic syndrome.The histology of MLN is very similar t...Membranous lupus nephritis(MLN),class V,is a distinct LN characterized by immune complex deposition on subepithelial kidney biopsy.MLN is often associated with nephrotic syndrome.The histology of MLN is very similar to idiopathic(primary)membranous nephropathy(pMN).However,MLN usually has abundant mesa-glomerular deposits absent in primary membranous nephropathy.The clinical manifestations,management,and prognosis of MLN differ from other types of LN(type III,IV,or mixed type III/IV+V).Although immunosuppressive therapy is often necessary for MLN,the optimal treatment regimen is yet to be determined.This review summarizes the progress in the diagnosis and treatment of MLN and discusses the selection of immunosuppressants for MLN.展开更多
BACKGROUND Complement overactivation is a major driver of lupus nephritis(LN).Impaired interactions of C-reactive protein(CRP)with complement factor H(CFH)have been shown as a pathogenic mechanism that contributes to ...BACKGROUND Complement overactivation is a major driver of lupus nephritis(LN).Impaired interactions of C-reactive protein(CRP)with complement factor H(CFH)have been shown as a pathogenic mechanism that contributes to the overactivation of complement in LN.However,genetic variations of neither CRP nor CFH show consistent influences on the risk of LN.AIM To examine whether genetic variations of CRP and CFH in combination can improve the risk stratification in Chinese population.METHODS We genotyped six CRP single nucleotide polymorphisms(SNPs)(rs1205,rs3093062,rs2794521,rs1800947,rs3093077,and rs1130864)and three CFH SNPs(rs482934,rs1061170,and rs1061147)in 270 LN patients and 303 healthy subjects.RESULTS No linkage was found among CRP and CFH SNPs,indicating lack of genetic interactions between the two genes.Moreover,CRP and CFH SNPs,neither individually nor in combination,are associated with the risk or clinical manifestations of LN.Given the unambiguous pathogenic roles of the two genes.CONCLUSION These findings suggest that the biological effects of most genetic variations of CRP and CFH on their expressions or activities are not sufficient to influence the disease course of LN.展开更多
Purpose:To explore the traditional Chinese medicine(TCM)regulates ferroptosis key genes in the occurrence and development of lupus nephritis(LN)based on biological information database.Patients and methods:Ferroptosis...Purpose:To explore the traditional Chinese medicine(TCM)regulates ferroptosis key genes in the occurrence and development of lupus nephritis(LN)based on biological information database.Patients and methods:Ferroptosis related genes were identified based on FerrDb database and literature retrieval.Used the OMIM,Gene Cards,Drug Bank to obtain the targets of LN.Cytoscapes 3.8.2 software and STRING database were used to analyze protein-protein interaction(PPI)network.Metacape software and Weishengxin were used to analyze the gene ontology(GO)classification and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.UniProt Database and Traditional Chinese Systems Pharmacology Database and Analysis Platform analysis platform were used to obtain the data table of key TCM and related targets.Cytoscapes 3.8.2 software was used to analyze the PPI network.Results:A total of 401 ferroptosis-related genes,361 LN related genes and 21“Ferroptosis-LN”intersection genes were obtained.Ferroptosis in the occurrence and prognosis of LN mainly involved the inflammatory response,cell activation,positive regulation of chemokine production and it was mainly involved in necroptosis,inflammatory bowel disease,ferroptosis and other pathways.A total of 412 TCMs containing key genes of“Ferroptosis-LN”were acquired.The most key genes were contained in Mahuang,Gehua,Baiguo,Chuanniuxi,Jinyinhua.15 key genes of“TCM-LN”were obtained.5 ferroptosis-related key genes in LN regulated by TCM were obtained,which were IL1β,TLR4,IFNG,STAT3 and HMOX1.Conclusion:TCM,such as Mahuang,Gehua,Baiguo,Chuanniuxi,Jinyinhua,may affect the occurrence and development of LN through the key ferroptosis genes,such as IL1B,TLR4,IFNG,STAT3 and HMOX1.展开更多
Objective:To evaluate the effects of rituximab versus mycophenolate mofetil or cyclophosphamide as control in lupus nephritis by meta-analysis.Methods:A systematic search was carried out up to January 2022,obtaining 7...Objective:To evaluate the effects of rituximab versus mycophenolate mofetil or cyclophosphamide as control in lupus nephritis by meta-analysis.Methods:A systematic search was carried out up to January 2022,obtaining 7 studies involving 645 participants with lupus nephritis at the commencement of the investigation;198 of them were treated with rituximab,while 447 were treated with mycophenolate mofetil or cyclophosphamide.We determined the odds ratio(OR)and mean difference(MD)with 95%confidence index(CI)to compare rituximab’s efficacy to that of mycophenolate mofetil or cyclophosphamide as control in lupus nephritis using random-or fixed-effects model by dichotomous or continuous techniques.Results:The rituximab group showed significantly higher complete renal remission rate(OR=2.52;95%CI 1.30-4.91,P=0.006)and total renal remission rates(OR=2.22;95%CI 1.36-3.63,P=0.001)than the control group.However,there was no significant difference in terms of end Systemic Lupus Erythematosus Disease Activity Index(SLEDAI)score(MD-1.16;95%CI-2.88-0.57,P=0.19),proteinuria(MD-0.31;95%CI-0.70-0.09,P=0.013),and serum creatinine(MD 0.01;95%CI-0.04-0.07,P=0.64)between the rituximab group and the control.Conclusion:Rituximab exhibited significantly greater complete renal remission rate and total renal remission rates,with no significant difference in terms of shorter-end SLEDAI,proteinuria,and serum creatinine,compared with the control in individuals with lupus nephritis.展开更多
BACKGROUND Patients with lupus nephritis(LN)typically undergo long-term treatment with glucocorticoids(GCs)and immunosuppressants.There is a growing demand for optimal therapy with better remission results and fewer s...BACKGROUND Patients with lupus nephritis(LN)typically undergo long-term treatment with glucocorticoids(GCs)and immunosuppressants.There is a growing demand for optimal therapy with better remission results and fewer side effects.Sustained traditional Chinese medicine(TCM)might be quite valuable for multitarget therapy,reducing the total dosage of GCs and minimizing the side effects of immunosuppressants.AIM To evaluate whether Dan Bai Xiao Formula(DBXF)can reduce the exposure to GCs and cyclophosphamide(CYC)and to assess the efficacy and safety of DBXF for the resolution of proteinuria and hematuria in children with LN.METHODS A 24-wk pilot study was conducted at Beijing Children’s Hospital.Children with active LN were divided into either a TCM group or a control group.Children in the TCM group received DBXF combined with GCs and CYC,and the ones in the control group received GCs and CYC every 4 wk for 24 wk.The primary endpoints of this trial were urinary protein excretion of<150 mg/d and normal serum albumin concentration and renal function.RESULTS The trial included 78 children,of whom 38 received GCs and CYC treatment(control group)and the remaining 40 received DBXF combined with GCs and CYC treatment(TCM group).At week 24,the TCM group showed a better rate of complete remission(42.5%);however,there was no significant difference compared with the control group(31.5%,P>0.05).The urine red blood cell count and urine protein level were significantly lower in the TCM group than in the control group at weeks 4,12,and 24(P<0.05).Furthermore,patients in the TCM group had a lower proportion of methylprednisolone pulses than those in the control group(1.30±1.41 vs 3.05±2.02,P<0.0001).The ending GC dose was significantly lower in the TCM group than in the control group(P<0.001).Moreover,more hepatic function damage,gastrointestinal adverse effects,and hypertension were observed in the control group than in the TCM group(P<0.05).CONCLUSION The findings suggest that DBXF treatment is effective and safe as a supplementary therapy for LN and is superior to routine GC and CYC therapy.DBXF containing combination treatment possibly results in a faster resolution of proteinuria and hematuria,smoother GC reduction,fewer methylprednisolone pulses,and fewer adverse events.展开更多
BACKGROUND Alport syndrome(ATS)is a rare hereditary disease caused by mutations in genes such as COL4A3,COL4A4,and COL4A5.ATS involves a spectrum of phenotypes ranging from isolated hematuria that is nonprogressive to...BACKGROUND Alport syndrome(ATS)is a rare hereditary disease caused by mutations in genes such as COL4A3,COL4A4,and COL4A5.ATS involves a spectrum of phenotypes ranging from isolated hematuria that is nonprogressive to progressive renal disease with extrarenal abnormalities.Although ATS can be combined with other diseases or syndromes,ATS combined with lupus nephritis has not been reported before.CASE SUMMARY A Chinese family with ATS was recruited for the current study.Clinical characteristics(including findings from renal biopsy)of ATS patients were collected from medical records,and potential causative genes were explored by whole-exome sequencing.A heterozygous substitution in intron 22 of COL4A3(NM_000091 c.2657-1G>A)was found in the patients,which was further confirmed by quantitative polymerase chain reaction.CONCLUSION Heterozygous substitution of a COL4A3 gene splice site was identified by wholeexome sequencing,revealing the molecular pathogenic basis of this disorder.In general,identification of pathogenic genes can help to fully understand the molecular mechanism of disease and facilitate precise treatment.展开更多
BACKGROUND Downgrading target treatment and laparoscopic partial nephrectomy have become increasingly popular in patients with renal cell carcinomas.Rare as it is,pneumothorax is one of the most severe intraoperative ...BACKGROUND Downgrading target treatment and laparoscopic partial nephrectomy have become increasingly popular in patients with renal cell carcinomas.Rare as it is,pneumothorax is one of the most severe intraoperative complications which needs immediate recognition.On the other hand,as a rheumatological disease,lupus nephritis requires a long period of hormone therapy.Cases of pneumothorax in hormone-consuming renal cancer patients are even fewer.CASE SUMMARY A 39-year-old woman was admitted to our department to take a laparoscopic partial nephrectomy.The patient had a medical history of lupus nephritis and renal clear cell carcinoma with hormone and target treatment.Her blood oxygen saturation dropped to 92%during the operation,and pneumothorax was detected by ultrasound.O2 inhalation and lung dilation were performed.Her vital signs were monitored closely throughout the operation.The operation was accomplished,and she regained consciousness smoothly.A postoperative bedside chest X-ray was conducted after she was transferred to the urosurgery ward,while no evidence of further pneumothorax or lib injury was observed.CONCLUSION Pneumothorax is a severe complication in laparoscopic or robotic-assisted laparoscopic operations,especially in retroperitoneal ones.It is easily neglected unless the injury of the diaphragm is found.Low insufflation pressure and shorter operation time are necessary for patients with a history of long-term hormone consumption or chronic immune system disease.展开更多
<strong>Background: </strong>Lupus nephritis (LN) is one of the most common presentations of Systemic lupus erythematosus (SLE). Cyclophosphamide is one of the key immunosuppressive agents for the manageme...<strong>Background: </strong>Lupus nephritis (LN) is one of the most common presentations of Systemic lupus erythematosus (SLE). Cyclophosphamide is one of the key immunosuppressive agents for the management of LN. Leflunomide is an isoxazole immunomodulatory agent has been shown to be safe, well tolerated and effective in SLE and LN. <strong>Objective: </strong>To evaluate the outcome of leflunomide in the treatment of proliferative lupus nephritis compared to cyclophosphamide. <strong>Method: </strong>This randomized clinical trial was held in Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from July 2017 to August 2019. A total of 66 patients of proliferative lupus nephritis who need induction therapy were enrolled in this study. Leflunomide 100 mg/day for consecutive 3 days followed by 0.5 mg/kg/day in divided dose was given in experimental group (n = 32) and intravenous cyclophosphamide 0.5 gm/m2 of body surface area monthly pulse was given in control group (n = 34). All study patients have received prednisolone and hydroxychloroquine according to KDIGO guideline then followed up monthly for 6 months. Outcomes were measured at 6th month by renal function [S. Creatinine, 24 hours urinary total protein (24-hr UTP)], changes in SELENA-SLEDAI score, anti-ds DNA level, serum complement levels (serum C3 & C4), remission (complete/partial) and adverse drug responses.<strong> Result:</strong> In experimental group, remission occurred in 18 (56.3%) patients and no remission in 14 (43.7%) patients. In control group, remission occurred in 24 (70.6%) patients and no remission in 10 (29.4%) patients. Adverse effects in experimental group were: elevated ALT (6.3%), hypertension (12.5%), infection (6.3%) and amenorrhea (12.5%). In control group, adverse effects were mainly leucopenia (5.9%), infection (17.7%) and amenorrhea (29.4%). Intergroup analysis for treatment responses and adverse effects showed no significant difference (p > 0.05). <strong>Conclusion:</strong> Leflunomide combined with prednisolone is effective in the induction treatment of proliferative lupus nephritis in Bangladeshi patients in terms of response rate and adverse effects.展开更多
Most of the literature focused on the proliferative forms of the lupic Glomerulonephritis. Clinicians are increasingly confronted with cases of lupic nephropathy purely mesangial (class II). The aim of our study is to...Most of the literature focused on the proliferative forms of the lupic Glomerulonephritis. Clinicians are increasingly confronted with cases of lupic nephropathy purely mesangial (class II). The aim of our study is to describe the mode of presentation of the class II Lupus nephropathy, evaluate its evolutionary profile, and investigate possible risk factors for therapeutic misresponse, relapse or histological transformation. This is a retrospective descriptive and analytical study conducted in nephrology depratement at the Hassan II university hospital Fez from January 2009 until September 2018. We included 20 patients. The average age was 33.8 ± 7.25 years [22 - 50 years]. Nephropathy was inaugurated in half of the cases. The mean time of onset of nephropathy in relation to the lupic disease was 36.7 ± 45.4 months [1 - 144 months]. The main reason for consultation was non-nephrotic proteinuria (65%). Renal failure revealed diagnosis in three patients. All patients had a positive immunologic assessment. 90% of our patients received oral corticosteroid therapy with immunosuppressive therapy in 3 cases. Remission has been noted in all of our patients. After an average follow-up period of 39 ± 23 months [6 - 92 months], 45% relapsed. A second biopsy was performed in 80% of patients showing histologic transformation in four patients, requiring immunosuppressive therapy. The analytical study showed that the occurrence of relapse was significantly related to the presence of a known Lupus and its seniority. Proteinuria at 12 months was also significantly higher in the relapsed group. One patient died as a result of neurological complications. Another has Evolved into chronic end stage renal failure and has been put on hemodialysis.展开更多
<strong>Introduction:</strong> The prevalence of infections in patients with systemic lupus erythematosus ranges from 26% to 78%. Patients with systemic lupus erythematosus are particularly susceptible to ...<strong>Introduction:</strong> The prevalence of infections in patients with systemic lupus erythematosus ranges from 26% to 78%. Patients with systemic lupus erythematosus are particularly susceptible to infections due to a dysfunction of immune response and the immunosuppressive therapy. <strong>Patients and method:</strong> We carried out this study with the aim of describing the prevalence of infections in lupus nephritis and determining the associated risk factors. This was a multi-center, observational, retrospective, descriptive and analytical study over a 10-year period from November 1, 2010 to October 31, 2020. The study was carried out in the nephrology departments of six hospitals in Dakar. <strong>Results:</strong> During the study period, 98 patients were included. The mean age was 32.32 ± 11.33 years with a sex ratio of 0.21. Among the included patients, fifty-four (55.1%) had at least one infectious episode, of which 53.7% had 1 infection, 24.1% had 2 infectious episodes and 22.2% had 3 infectious episodes. The overall incidence was 55.1 infections per 100 patient-years. 57.2% of these infectious episodes occurred within the first six months after the lupus was diagnosed. The main sites of infection were urinary (30.7%), gastrointestinal (22.0%) and pleuropulmonary (16.5%). The incriminated germ was a bacterium in 78.18% of cases, a virus in 5.46%, a parasite in 9.09 and a fungus in 7.27. The most frequently germ found was <i>Escherichia coli</i> (29.09%). The evolution was marked by recovery in 93.4% of cases. Deaths occurred in 15 patients of which 33.3% were related to infections. Factor significantly associated with the onset of infection in multivariate analysis was the presence of a proliferative class of lupus nephritis (p = 0.013). <strong>Conclusion:</strong> Infections were common during lupus nephritis. The presence of a proliferative class was risk factors for infection.展开更多
<strong>Background: </strong>Systemic lupus erythematosus and lupus nephritis are relatively common autoimmune diseases that can cause damage to multiple systems. <strong>Aim:</strong> To inves...<strong>Background: </strong>Systemic lupus erythematosus and lupus nephritis are relatively common autoimmune diseases that can cause damage to multiple systems. <strong>Aim:</strong> To investigate the lupus activity of patients with lupus nephritis on hemodialysis and the combined occurrence of lupus panniculitis. <strong>Case introduction: </strong>A patient with lupus nephritis on regular hemodialysis had a symmetrical hard mass under the skin of his abdomen. After surgical resection and pathological examination, she was diagnosed with lupus panniculitis and was treated with glucocorticoids and hydroxychloroquine. After that, no new subcutaneous masses appeared, and the unresectable part of the masses did not increase.<strong> Conclusion:</strong> 1) Lupus activities in patients with lupus nephritis entering end-stage renal disease still need to be paid attention to. 2) Lupus panniculitis can occur on the skin of the abdomen, and it needs to be differentiated from connective tissue panniculitis, sclerosing panniculitis and other diseases.展开更多
Lupus nephritis(LN),an immune complex-mediated glomerulonephritis,is one of the most severe complications of systemic lupus erythematosus.Current therapeutic regimens for LN mainly involve nonspecific immunosuppressan...Lupus nephritis(LN),an immune complex-mediated glomerulonephritis,is one of the most severe complications of systemic lupus erythematosus.Current therapeutic regimens for LN mainly involve nonspecific immunosuppressants and biologics targeting immune cells,but these treatments are not always effective and some patients are nonresponsive and susceptible to recurrence.Podocytes are essential for maintaining the glomerular filtration barrier.Injury to and loss of podocytes lead to proteinuria,a hallmark of renal involvement and LN.Podocytes are,therefore,emerging as prospective therapeutic targets for LN.There are numerous mechanisms underlying podocyte malfunction in LN,with autophagy,mitochondrial dysregulation,and programmed cell death being the main processes behind podocyte loss.This review summarizes recent advances in understanding podocyte dysfunction in LN pathogenesis and discusses potential therapeutic interventions targeting podocytes in LN.展开更多
Autoantibodies produced by B cells play a pivotal role in the pathogenesis of systemic lupus erythematosus (SLE). However, both the cellular source of antiphospholipid antibodies and their contributions to the develop...Autoantibodies produced by B cells play a pivotal role in the pathogenesis of systemic lupus erythematosus (SLE). However, both the cellular source of antiphospholipid antibodies and their contributions to the development of lupus nephritis (LN) remain largely unclear. Here, we report a pathogenic role of anti-phosphatidylserine (PS) autoantibodies in the development of LN. Elevated serum PS-specific IgG levels were measured in model mice and SLE patients, especially in those with LN. PS-specific IgG accumulation was found in the kidney biopsies of LN patients. Both transfer of SLE PS-specific IgG and PS immunization triggered lupus-like glomerular immune complex deposition in recipient mice. ELISPOT analysis identified B1a cells as the main cell type that secretes PS-specific IgG in both lupus model mice and patients. Adoptive transfer of PS-specific B1a cells accelerated the PS-specific autoimmune response and renal damage in recipient lupus model mice, whereas depletion of B1a cells attenuated lupus progression. In culture, PS-specific B1a cells were significantly expanded upon treatment with chromatin components, while blockade of TLR signal cascades by DNase I digestion and inhibitory ODN 2088 or R406 treatment profoundly abrogated chromatin-induced PS-specific IgG secretion by lupus B1a cells. Thus, our study has demonstrated that the anti-PS autoantibodies produced by B1 cells contribute to lupus nephritis development. Our findings that blockade of the TLR/Syk signaling cascade inhibits PS-specific B1-cell expansion provide new insights into lupus pathogenesis and may facilitate the development of novel therapeutic targets for the treatment of LN in SLE.展开更多
Background:Systemic lupus erythematosus(SLE)is a complex systemic autoimmune disease characterized by development of autoantibodies and multiorgan involvement.Kidney involvement,termed lupus nephritis,has major impact...Background:Systemic lupus erythematosus(SLE)is a complex systemic autoimmune disease characterized by development of autoantibodies and multiorgan involvement.Kidney involvement,termed lupus nephritis,has major impact on life expectancy.It is increasingly recognized that SLE is likely a common clinical manifestation of pathophysiologically diverse processes,and lupus nephritis has similarly been associated with several distinct immunological processes.We compared the immune cell phenotypes of individuals with SLE in the presence or absence of nephritis.Methods:Cryopreserved peripheral blood mononuclear cells from SLE patients with and without kidney involvement underwent flow cytometric analysis to identify major populations in T cells,B cells and myeloid lineages.Results:We compared the frequencies of lymphocyte populations in 69 SLE patients without nephritis,20 SLE patients with nephritis,and 92 healthy blood donors.Patients with SLE and lupus nephritis(LN)had reduced marginal zone B cells(P<0.0001 in SLE;P=0.001 in LN),memory B cells(P=0.002 in SLE;P=0.001 in LN)and circulating T follicular helper(Tfh)memory cells(P<0.0001 in SLE and LN)compared to healthy donors.Patients with lupus nephritis had increase Th2(P<0.0001)and T regulatory cells(P<0.0001)compared to both SLE patients without nephritis and healthy donors.Conclusion:SLE patients with and without lupus nephritis have distinct immunologic differences that may reflect the unique pathophysiological processes contributing to disease manifestations.展开更多
To evaluate apoptosis in lupus nephritis and the relationship between the existence of apoptotic cells in renal tissue and histopathological or clinical changes Methods Apoptosis was detected by in situ nick end label...To evaluate apoptosis in lupus nephritis and the relationship between the existence of apoptotic cells in renal tissue and histopathological or clinical changes Methods Apoptosis was detected by in situ nick end labeling techniques (TUNEL) in renal biopsies from 25 patients with type Ⅳ lupus nephritis (LN), 12 patients with IgA nephropathy IgAN, 4 patients with idiopathic mesangioproliferative glomerulonephritis (MsPGN) and 3 patients with acute poststreptococcal glomerulonephritis (APGN) Normal renal tissue obtained at nephrectomy for hypernephroma in 4 adults was used as control Proliferating cells were identified by proliferating cell nuclear antigen (PCNA) in these patients Results Compared to other proliferative glomerulo^nephritis and controls, the patients with lupus nephritis had less apoptotic cells, a higher ratio of PCNA+ cells/TdT+ cells (P/T) in renal tissues; and their P/T ratio in glomeruli and tubulointerstitium correlated with the chronicity index, r =0 4983 ( P =0 0132), r =0 8399 ( P <0 001), r =0 6614 ( P =0 0033), respectively P/T ratios in the glomerulus and tubule had a positive correlation with 24 hour urinary protein, r =0 8554 ( P <0 001) and r =0 7134 ( P =0 001); and a negative correlation with creatinine clearance (Ccr), r =-0 4880 ( P =0 0133) and r =-0 7229 ( P =0 001), which in tubules positively correlated with serum creatinine (Scr), r =0 4107 ( P =0 0414) Conclusions Apoptosis is reduced in proliferative lupus nephritis Intense proliferation without a commensurate increase in apoptosis is a possible mechanism that leads to chronic progressive renal histopathological展开更多
OBJECTIVE:To investigate the effectiveness and safety of tripterygium glycosides(TG)tablet(雷公藤多苷片)for the treatment of Lupus nephritis(LN).METHODS:Several databases were systematically searched including Pub Med...OBJECTIVE:To investigate the effectiveness and safety of tripterygium glycosides(TG)tablet(雷公藤多苷片)for the treatment of Lupus nephritis(LN).METHODS:Several databases were systematically searched including Pub Med,Embase,Cochrane,Wiley,China National Knowledge Infrastructure Database,Sino Med and Wanfang Library till June 20,2020.Revman5.3 was utilized to analyze the data according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement.RESULTS:In total,8 randomized controlled trials involving 583 participants were identified.Meta-analyses showed that,compared with glucocorticoids(GC)alone,the combination with TG tablet provided a statistically significant improvement in total remission(TR)(RR=1.27,95%CI:1.08–1.50,P=0.004),complete remission(CR)(RR=1.61,95%CI:1.05–2.47,P=0.03)and C3 levels(WMD=0.27,95%CI:0.14–0.39,P<0.0001),C4 levels(WMD=0.12,95%CI:0.07–0.17,P<0.00001).No significant differences were seen in TR,CR,proteinuria,serum creatinine,C3 and C4(TR:RR=1.00,95%CI:0.87–1.16,P=0.95;CR:RR=1.10,95%CI:0.78–1.56,P=0.58;proteinuria levels:WMD=-0.06,95%CI:-0.13 to 0.01,P=0.10;serum creatinine levels:WMD=-0.01,95%CI:-7.36 to 7.35,P=1.00;C3 levels:WMD=0.01,95%CI:-0.06 to 0.07,P=0.84;C4 levels:WMD=-0.01,95%CI:-0.03 to 0.01,P=0.49)between azathioprine(AZA)/leflomit(LEF)+GC and TG tablet+GC.Adverse events(hepatic dysfunction,nausea,vomitting)showed no statistical differences between the TG tablet+GC group and the GC group.There were more new onset of irregular menstruation in the TG tablet+GC group than those in the AZA+GC(RR=3.57,95%CI:1.40–9.11,P=0.008)/LEF+GC(RR=6.69,95%CI:2.42-18.46,P=0.0002)group,but leucopenia lower than those in AZA+GC group(RR=0.38,95%CI:0.17-0.85,P=0.02)and alopecia(RR=0.14,95%CI:0.03-0.77,P=0.02)and rash(RR=0.09,95%CI:0.01-0.69,P=0.02)lower than those in LEF+GC group.Conclusions:This review indicates that TG tablet maybe effective in LN treatment.Nevertheless,adverse events cannot be ignored.Large sample,multi-center,highquality clinical studies are needed to verify the exact effects and safety of TG tablet in treatment of LN.展开更多
This study aimed to evaluate the efficacy and safety of mycophenolate mofetil(MMF)or tacrolimus(TAC)compared with azathioprine(AZA)as maintenance therapy for active lupus nephritis(ALN).Patients with ALN who responded...This study aimed to evaluate the efficacy and safety of mycophenolate mofetil(MMF)or tacrolimus(TAC)compared with azathioprine(AZA)as maintenance therapy for active lupus nephritis(ALN).Patients with ALN who responded to 24 weeks of induction treatment were enrolled.Patients who received MMF or TAC as induction therapy continued MMF or TAC treatment during the maintenance period,whereas those who received intravenous cyclophosphamide were subjected to AZA treatment.The primary endpoint was the incidence of renal relapse.Secondary endpoints included extrarenal flares and composite endpoints(deaths,end-stage renal disease,or doubling of serum creatinine levels).A total of 123 ALN patients(47 in the MMF group,37 in the TAC group,and 39 in the AZA group)were enrolled.The median follow-up time was 60 months.Ten MMF-treated patients,ten TAC-treated patients,and eight AZA-treated patients experienced renal relapses(P=0.844).The cumulative renal relapse rates in the MMF group(P=0.934)and TAC group(P=0.673)were similar to the renal relapse rate in the AZA group.No significant difference in the incidence of severe adverse event was observed among the groups.Long-term maintenance therapies with MMF or TAC might have similarly low rates of renal relapse and similar safety profiles compared with AZA.展开更多
Lupus nephritis(LN) has a high incidence in systemic lupus erythematosus(SLE) patients, but there is a lack of sensitive predictive markers. The purpose of the study was to investigate the association between the CD4^...Lupus nephritis(LN) has a high incidence in systemic lupus erythematosus(SLE) patients, but there is a lack of sensitive predictive markers. The purpose of the study was to investigate the association between the CD4^(+)CD8^(+)double positive T(DPT) lymphocytes and LN. The study included patients with SLE without renal impairment(SLE-NRI), LN, nephritic syndrome(NS), or nephritis. Peripheral blood lymphocyte subsets were analyzed by flow cytometry. Biochemical measurements were performed with peripheral blood in accordance with the recommendations proposed by the National Center for Clinical Laboratories. The proportions of DPT cells in the LN group were significantly higher than that in the SLE-NRI group(t=4.012, P<0.001), NS group(t=3.240,P=0.001), and nephritis group(t=2.57, P=0.011). In the LN group, the risk of renal impairment increased significantly in a DPT cells proportion-dependent manner. The risk of LN was 5.136 times(95% confidence interval, 2.115–12.473) higher in cases with a high proportion of DPT cells than those whose proportion of DPT cells within the normal range. These findings indicated that the proportion of DPT cells could be a potential marker to evaluate LN susceptibility, and the interference of NS and nephritis could be effectively excluded when assessing the risk of renal impairment during SLE with DPT cell proportion.展开更多
Background:Systemic lupus erythematosus(SLE)is a complex chronic autoimmune disease with no known cure.However,the regulatory mechanism of immunity-related genes is not fully understood in SLE.In order to explore new ...Background:Systemic lupus erythematosus(SLE)is a complex chronic autoimmune disease with no known cure.However,the regulatory mechanism of immunity-related genes is not fully understood in SLE.In order to explore new therapeutic targets,we used bioinformatical methods to analyze a series of data.Methods:After downloading and processing the data from Gene Expression Omnibus database,the differentially expressed genes of SLE were analyzed.CIBERSORT algorithm was used to analyze the immune infiltration of SLE.Based on single-cell RNA-sequencing data,the role of immune-related genes in SLE and its target organ(kidney)were analyzed.Key transcription factors affecting immune-related genes were identified.Cell-cell communication networks in SLE were analyzed.Results:In total,15 hub genes and 4 transcription factors were found in the bulk data.Monocytes and macrophages in GSE81622(SLE)showed more infiltration.There were four cell types were annotated in scRNA sequencing dataset(GSE135779),as follows T cells,monocyte,NK cells and B cells.Immunity-related genes were overexpressed in monocytes.Conclusion:The present study shows that immune-related genes affect SLE through monocytes and play an important role in target organ renal injury.展开更多
基金Supported by National Natural Science Foundation of China,No.81960136the Science and Technology Department of Yunnan Province,No.202101AT070243.
文摘BACKGROUND In this study,we retrospectively analysed macrophage infiltration and podocyte injury in three patients with diffuse proliferative lupus nephritis(LN)who un-derwent repeated renal biopsy.CASE SUMMARY Clinical data of three diffuse proliferative LN patients with different pathological characteristics(case 1 was LN IV-G(A),case 2 was LN IV-G(A)+V,and case 3 was LN IV-G(A)+thrombotic microangiopathy)were reviewed.All patients underwent repeated renal biopsies 6 mo later,and renal biopsy specimens were studied.Macrophage infiltration was assessed by CD68 expression detected by immunohistochemical staining,and an immunofluorescence assay was used to detect podocin expression to assess podocyte damage.After treatment,Case 1 changed to LN III-(A),Case 2 remained as type V LN lesions,and Case 3,which changed to LN IV-S(A),had the worst prognosis.We observed reduced macro-phage infiltration after therapy.However,two of the patients with active lesions after treatment still showed macrophage infiltration in the renal interstitium.Before treatment,the three patients showed discontinuous expression of podocin.Notably,the integrity of podocin was restored after treatment in Case 1.CONCLUSION It may be possible to reverse podocyte damage and decrease the infiltrating ma-crophages in LN patients through effective treatment.
文摘Membranous lupus nephritis(MLN),class V,is a distinct LN characterized by immune complex deposition on subepithelial kidney biopsy.MLN is often associated with nephrotic syndrome.The histology of MLN is very similar to idiopathic(primary)membranous nephropathy(pMN).However,MLN usually has abundant mesa-glomerular deposits absent in primary membranous nephropathy.The clinical manifestations,management,and prognosis of MLN differ from other types of LN(type III,IV,or mixed type III/IV+V).Although immunosuppressive therapy is often necessary for MLN,the optimal treatment regimen is yet to be determined.This review summarizes the progress in the diagnosis and treatment of MLN and discusses the selection of immunosuppressants for MLN.
文摘BACKGROUND Complement overactivation is a major driver of lupus nephritis(LN).Impaired interactions of C-reactive protein(CRP)with complement factor H(CFH)have been shown as a pathogenic mechanism that contributes to the overactivation of complement in LN.However,genetic variations of neither CRP nor CFH show consistent influences on the risk of LN.AIM To examine whether genetic variations of CRP and CFH in combination can improve the risk stratification in Chinese population.METHODS We genotyped six CRP single nucleotide polymorphisms(SNPs)(rs1205,rs3093062,rs2794521,rs1800947,rs3093077,and rs1130864)and three CFH SNPs(rs482934,rs1061170,and rs1061147)in 270 LN patients and 303 healthy subjects.RESULTS No linkage was found among CRP and CFH SNPs,indicating lack of genetic interactions between the two genes.Moreover,CRP and CFH SNPs,neither individually nor in combination,are associated with the risk or clinical manifestations of LN.Given the unambiguous pathogenic roles of the two genes.CONCLUSION These findings suggest that the biological effects of most genetic variations of CRP and CFH on their expressions or activities are not sufficient to influence the disease course of LN.
基金supported by National Natural Science Foundation of China[grant numbers 8216087881960866].
文摘Purpose:To explore the traditional Chinese medicine(TCM)regulates ferroptosis key genes in the occurrence and development of lupus nephritis(LN)based on biological information database.Patients and methods:Ferroptosis related genes were identified based on FerrDb database and literature retrieval.Used the OMIM,Gene Cards,Drug Bank to obtain the targets of LN.Cytoscapes 3.8.2 software and STRING database were used to analyze protein-protein interaction(PPI)network.Metacape software and Weishengxin were used to analyze the gene ontology(GO)classification and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.UniProt Database and Traditional Chinese Systems Pharmacology Database and Analysis Platform analysis platform were used to obtain the data table of key TCM and related targets.Cytoscapes 3.8.2 software was used to analyze the PPI network.Results:A total of 401 ferroptosis-related genes,361 LN related genes and 21“Ferroptosis-LN”intersection genes were obtained.Ferroptosis in the occurrence and prognosis of LN mainly involved the inflammatory response,cell activation,positive regulation of chemokine production and it was mainly involved in necroptosis,inflammatory bowel disease,ferroptosis and other pathways.A total of 412 TCMs containing key genes of“Ferroptosis-LN”were acquired.The most key genes were contained in Mahuang,Gehua,Baiguo,Chuanniuxi,Jinyinhua.15 key genes of“TCM-LN”were obtained.5 ferroptosis-related key genes in LN regulated by TCM were obtained,which were IL1β,TLR4,IFNG,STAT3 and HMOX1.Conclusion:TCM,such as Mahuang,Gehua,Baiguo,Chuanniuxi,Jinyinhua,may affect the occurrence and development of LN through the key ferroptosis genes,such as IL1B,TLR4,IFNG,STAT3 and HMOX1.
文摘Objective:To evaluate the effects of rituximab versus mycophenolate mofetil or cyclophosphamide as control in lupus nephritis by meta-analysis.Methods:A systematic search was carried out up to January 2022,obtaining 7 studies involving 645 participants with lupus nephritis at the commencement of the investigation;198 of them were treated with rituximab,while 447 were treated with mycophenolate mofetil or cyclophosphamide.We determined the odds ratio(OR)and mean difference(MD)with 95%confidence index(CI)to compare rituximab’s efficacy to that of mycophenolate mofetil or cyclophosphamide as control in lupus nephritis using random-or fixed-effects model by dichotomous or continuous techniques.Results:The rituximab group showed significantly higher complete renal remission rate(OR=2.52;95%CI 1.30-4.91,P=0.006)and total renal remission rates(OR=2.22;95%CI 1.36-3.63,P=0.001)than the control group.However,there was no significant difference in terms of end Systemic Lupus Erythematosus Disease Activity Index(SLEDAI)score(MD-1.16;95%CI-2.88-0.57,P=0.19),proteinuria(MD-0.31;95%CI-0.70-0.09,P=0.013),and serum creatinine(MD 0.01;95%CI-0.04-0.07,P=0.64)between the rituximab group and the control.Conclusion:Rituximab exhibited significantly greater complete renal remission rate and total renal remission rates,with no significant difference in terms of shorter-end SLEDAI,proteinuria,and serum creatinine,compared with the control in individuals with lupus nephritis.
基金Supported by the Capital Health Research and Development of Special,No.CH2018-2-2092.
文摘BACKGROUND Patients with lupus nephritis(LN)typically undergo long-term treatment with glucocorticoids(GCs)and immunosuppressants.There is a growing demand for optimal therapy with better remission results and fewer side effects.Sustained traditional Chinese medicine(TCM)might be quite valuable for multitarget therapy,reducing the total dosage of GCs and minimizing the side effects of immunosuppressants.AIM To evaluate whether Dan Bai Xiao Formula(DBXF)can reduce the exposure to GCs and cyclophosphamide(CYC)and to assess the efficacy and safety of DBXF for the resolution of proteinuria and hematuria in children with LN.METHODS A 24-wk pilot study was conducted at Beijing Children’s Hospital.Children with active LN were divided into either a TCM group or a control group.Children in the TCM group received DBXF combined with GCs and CYC,and the ones in the control group received GCs and CYC every 4 wk for 24 wk.The primary endpoints of this trial were urinary protein excretion of<150 mg/d and normal serum albumin concentration and renal function.RESULTS The trial included 78 children,of whom 38 received GCs and CYC treatment(control group)and the remaining 40 received DBXF combined with GCs and CYC treatment(TCM group).At week 24,the TCM group showed a better rate of complete remission(42.5%);however,there was no significant difference compared with the control group(31.5%,P>0.05).The urine red blood cell count and urine protein level were significantly lower in the TCM group than in the control group at weeks 4,12,and 24(P<0.05).Furthermore,patients in the TCM group had a lower proportion of methylprednisolone pulses than those in the control group(1.30±1.41 vs 3.05±2.02,P<0.0001).The ending GC dose was significantly lower in the TCM group than in the control group(P<0.001).Moreover,more hepatic function damage,gastrointestinal adverse effects,and hypertension were observed in the control group than in the TCM group(P<0.05).CONCLUSION The findings suggest that DBXF treatment is effective and safe as a supplementary therapy for LN and is superior to routine GC and CYC therapy.DBXF containing combination treatment possibly results in a faster resolution of proteinuria and hematuria,smoother GC reduction,fewer methylprednisolone pulses,and fewer adverse events.
基金Supported by the Science and Technology Bureau of Jiulongpo District in Chongqing,No.2019-02-027-D.
文摘BACKGROUND Alport syndrome(ATS)is a rare hereditary disease caused by mutations in genes such as COL4A3,COL4A4,and COL4A5.ATS involves a spectrum of phenotypes ranging from isolated hematuria that is nonprogressive to progressive renal disease with extrarenal abnormalities.Although ATS can be combined with other diseases or syndromes,ATS combined with lupus nephritis has not been reported before.CASE SUMMARY A Chinese family with ATS was recruited for the current study.Clinical characteristics(including findings from renal biopsy)of ATS patients were collected from medical records,and potential causative genes were explored by whole-exome sequencing.A heterozygous substitution in intron 22 of COL4A3(NM_000091 c.2657-1G>A)was found in the patients,which was further confirmed by quantitative polymerase chain reaction.CONCLUSION Heterozygous substitution of a COL4A3 gene splice site was identified by wholeexome sequencing,revealing the molecular pathogenic basis of this disorder.In general,identification of pathogenic genes can help to fully understand the molecular mechanism of disease and facilitate precise treatment.
文摘BACKGROUND Downgrading target treatment and laparoscopic partial nephrectomy have become increasingly popular in patients with renal cell carcinomas.Rare as it is,pneumothorax is one of the most severe intraoperative complications which needs immediate recognition.On the other hand,as a rheumatological disease,lupus nephritis requires a long period of hormone therapy.Cases of pneumothorax in hormone-consuming renal cancer patients are even fewer.CASE SUMMARY A 39-year-old woman was admitted to our department to take a laparoscopic partial nephrectomy.The patient had a medical history of lupus nephritis and renal clear cell carcinoma with hormone and target treatment.Her blood oxygen saturation dropped to 92%during the operation,and pneumothorax was detected by ultrasound.O2 inhalation and lung dilation were performed.Her vital signs were monitored closely throughout the operation.The operation was accomplished,and she regained consciousness smoothly.A postoperative bedside chest X-ray was conducted after she was transferred to the urosurgery ward,while no evidence of further pneumothorax or lib injury was observed.CONCLUSION Pneumothorax is a severe complication in laparoscopic or robotic-assisted laparoscopic operations,especially in retroperitoneal ones.It is easily neglected unless the injury of the diaphragm is found.Low insufflation pressure and shorter operation time are necessary for patients with a history of long-term hormone consumption or chronic immune system disease.
文摘<strong>Background: </strong>Lupus nephritis (LN) is one of the most common presentations of Systemic lupus erythematosus (SLE). Cyclophosphamide is one of the key immunosuppressive agents for the management of LN. Leflunomide is an isoxazole immunomodulatory agent has been shown to be safe, well tolerated and effective in SLE and LN. <strong>Objective: </strong>To evaluate the outcome of leflunomide in the treatment of proliferative lupus nephritis compared to cyclophosphamide. <strong>Method: </strong>This randomized clinical trial was held in Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from July 2017 to August 2019. A total of 66 patients of proliferative lupus nephritis who need induction therapy were enrolled in this study. Leflunomide 100 mg/day for consecutive 3 days followed by 0.5 mg/kg/day in divided dose was given in experimental group (n = 32) and intravenous cyclophosphamide 0.5 gm/m2 of body surface area monthly pulse was given in control group (n = 34). All study patients have received prednisolone and hydroxychloroquine according to KDIGO guideline then followed up monthly for 6 months. Outcomes were measured at 6th month by renal function [S. Creatinine, 24 hours urinary total protein (24-hr UTP)], changes in SELENA-SLEDAI score, anti-ds DNA level, serum complement levels (serum C3 & C4), remission (complete/partial) and adverse drug responses.<strong> Result:</strong> In experimental group, remission occurred in 18 (56.3%) patients and no remission in 14 (43.7%) patients. In control group, remission occurred in 24 (70.6%) patients and no remission in 10 (29.4%) patients. Adverse effects in experimental group were: elevated ALT (6.3%), hypertension (12.5%), infection (6.3%) and amenorrhea (12.5%). In control group, adverse effects were mainly leucopenia (5.9%), infection (17.7%) and amenorrhea (29.4%). Intergroup analysis for treatment responses and adverse effects showed no significant difference (p > 0.05). <strong>Conclusion:</strong> Leflunomide combined with prednisolone is effective in the induction treatment of proliferative lupus nephritis in Bangladeshi patients in terms of response rate and adverse effects.
文摘Most of the literature focused on the proliferative forms of the lupic Glomerulonephritis. Clinicians are increasingly confronted with cases of lupic nephropathy purely mesangial (class II). The aim of our study is to describe the mode of presentation of the class II Lupus nephropathy, evaluate its evolutionary profile, and investigate possible risk factors for therapeutic misresponse, relapse or histological transformation. This is a retrospective descriptive and analytical study conducted in nephrology depratement at the Hassan II university hospital Fez from January 2009 until September 2018. We included 20 patients. The average age was 33.8 ± 7.25 years [22 - 50 years]. Nephropathy was inaugurated in half of the cases. The mean time of onset of nephropathy in relation to the lupic disease was 36.7 ± 45.4 months [1 - 144 months]. The main reason for consultation was non-nephrotic proteinuria (65%). Renal failure revealed diagnosis in three patients. All patients had a positive immunologic assessment. 90% of our patients received oral corticosteroid therapy with immunosuppressive therapy in 3 cases. Remission has been noted in all of our patients. After an average follow-up period of 39 ± 23 months [6 - 92 months], 45% relapsed. A second biopsy was performed in 80% of patients showing histologic transformation in four patients, requiring immunosuppressive therapy. The analytical study showed that the occurrence of relapse was significantly related to the presence of a known Lupus and its seniority. Proteinuria at 12 months was also significantly higher in the relapsed group. One patient died as a result of neurological complications. Another has Evolved into chronic end stage renal failure and has been put on hemodialysis.
文摘<strong>Introduction:</strong> The prevalence of infections in patients with systemic lupus erythematosus ranges from 26% to 78%. Patients with systemic lupus erythematosus are particularly susceptible to infections due to a dysfunction of immune response and the immunosuppressive therapy. <strong>Patients and method:</strong> We carried out this study with the aim of describing the prevalence of infections in lupus nephritis and determining the associated risk factors. This was a multi-center, observational, retrospective, descriptive and analytical study over a 10-year period from November 1, 2010 to October 31, 2020. The study was carried out in the nephrology departments of six hospitals in Dakar. <strong>Results:</strong> During the study period, 98 patients were included. The mean age was 32.32 ± 11.33 years with a sex ratio of 0.21. Among the included patients, fifty-four (55.1%) had at least one infectious episode, of which 53.7% had 1 infection, 24.1% had 2 infectious episodes and 22.2% had 3 infectious episodes. The overall incidence was 55.1 infections per 100 patient-years. 57.2% of these infectious episodes occurred within the first six months after the lupus was diagnosed. The main sites of infection were urinary (30.7%), gastrointestinal (22.0%) and pleuropulmonary (16.5%). The incriminated germ was a bacterium in 78.18% of cases, a virus in 5.46%, a parasite in 9.09 and a fungus in 7.27. The most frequently germ found was <i>Escherichia coli</i> (29.09%). The evolution was marked by recovery in 93.4% of cases. Deaths occurred in 15 patients of which 33.3% were related to infections. Factor significantly associated with the onset of infection in multivariate analysis was the presence of a proliferative class of lupus nephritis (p = 0.013). <strong>Conclusion:</strong> Infections were common during lupus nephritis. The presence of a proliferative class was risk factors for infection.
文摘<strong>Background: </strong>Systemic lupus erythematosus and lupus nephritis are relatively common autoimmune diseases that can cause damage to multiple systems. <strong>Aim:</strong> To investigate the lupus activity of patients with lupus nephritis on hemodialysis and the combined occurrence of lupus panniculitis. <strong>Case introduction: </strong>A patient with lupus nephritis on regular hemodialysis had a symmetrical hard mass under the skin of his abdomen. After surgical resection and pathological examination, she was diagnosed with lupus panniculitis and was treated with glucocorticoids and hydroxychloroquine. After that, no new subcutaneous masses appeared, and the unresectable part of the masses did not increase.<strong> Conclusion:</strong> 1) Lupus activities in patients with lupus nephritis entering end-stage renal disease still need to be paid attention to. 2) Lupus panniculitis can occur on the skin of the abdomen, and it needs to be differentiated from connective tissue panniculitis, sclerosing panniculitis and other diseases.
基金Key Laboratory of National Health Commission,and Key Laboratory of Nephrology,Guangdong Province,Guangzhou,China,Grant/Award Numbers:2002B60118,2020B1212060028National Natural Science Foundation of China,Grant/Award Numbers:81970599,82170737。
文摘Lupus nephritis(LN),an immune complex-mediated glomerulonephritis,is one of the most severe complications of systemic lupus erythematosus.Current therapeutic regimens for LN mainly involve nonspecific immunosuppressants and biologics targeting immune cells,but these treatments are not always effective and some patients are nonresponsive and susceptible to recurrence.Podocytes are essential for maintaining the glomerular filtration barrier.Injury to and loss of podocytes lead to proteinuria,a hallmark of renal involvement and LN.Podocytes are,therefore,emerging as prospective therapeutic targets for LN.There are numerous mechanisms underlying podocyte malfunction in LN,with autophagy,mitochondrial dysregulation,and programmed cell death being the main processes behind podocyte loss.This review summarizes recent advances in understanding podocyte dysfunction in LN pathogenesis and discusses potential therapeutic interventions targeting podocytes in LN.
基金supported by funding for Chongqing International Institute for Immunology(2020YJC10)National Natural Science Foundation of China(81901635,82171782,82260326,81971464)+2 种基金Shenzhen Science and Technology Program(CYJ20210324114602008)Hong Kong Research Grants Council Theme-Based Research Scheme(T12-703/19 R)the Centre for Oncology and Immunology under the Health@InnoHK Initiative by the Innovation and Technology Commission,Hong Kong,China.
文摘Autoantibodies produced by B cells play a pivotal role in the pathogenesis of systemic lupus erythematosus (SLE). However, both the cellular source of antiphospholipid antibodies and their contributions to the development of lupus nephritis (LN) remain largely unclear. Here, we report a pathogenic role of anti-phosphatidylserine (PS) autoantibodies in the development of LN. Elevated serum PS-specific IgG levels were measured in model mice and SLE patients, especially in those with LN. PS-specific IgG accumulation was found in the kidney biopsies of LN patients. Both transfer of SLE PS-specific IgG and PS immunization triggered lupus-like glomerular immune complex deposition in recipient mice. ELISPOT analysis identified B1a cells as the main cell type that secretes PS-specific IgG in both lupus model mice and patients. Adoptive transfer of PS-specific B1a cells accelerated the PS-specific autoimmune response and renal damage in recipient lupus model mice, whereas depletion of B1a cells attenuated lupus progression. In culture, PS-specific B1a cells were significantly expanded upon treatment with chromatin components, while blockade of TLR signal cascades by DNase I digestion and inhibitory ODN 2088 or R406 treatment profoundly abrogated chromatin-induced PS-specific IgG secretion by lupus B1a cells. Thus, our study has demonstrated that the anti-PS autoantibodies produced by B1 cells contribute to lupus nephritis development. Our findings that blockade of the TLR/Syk signaling cascade inhibits PS-specific B1-cell expansion provide new insights into lupus pathogenesis and may facilitate the development of novel therapeutic targets for the treatment of LN in SLE.
基金The Canberra Hospital Private Practice FundNational Health and Medical Research CouncilThe Jacquot Foundation。
文摘Background:Systemic lupus erythematosus(SLE)is a complex systemic autoimmune disease characterized by development of autoantibodies and multiorgan involvement.Kidney involvement,termed lupus nephritis,has major impact on life expectancy.It is increasingly recognized that SLE is likely a common clinical manifestation of pathophysiologically diverse processes,and lupus nephritis has similarly been associated with several distinct immunological processes.We compared the immune cell phenotypes of individuals with SLE in the presence or absence of nephritis.Methods:Cryopreserved peripheral blood mononuclear cells from SLE patients with and without kidney involvement underwent flow cytometric analysis to identify major populations in T cells,B cells and myeloid lineages.Results:We compared the frequencies of lymphocyte populations in 69 SLE patients without nephritis,20 SLE patients with nephritis,and 92 healthy blood donors.Patients with SLE and lupus nephritis(LN)had reduced marginal zone B cells(P<0.0001 in SLE;P=0.001 in LN),memory B cells(P=0.002 in SLE;P=0.001 in LN)and circulating T follicular helper(Tfh)memory cells(P<0.0001 in SLE and LN)compared to healthy donors.Patients with lupus nephritis had increase Th2(P<0.0001)and T regulatory cells(P<0.0001)compared to both SLE patients without nephritis and healthy donors.Conclusion:SLE patients with and without lupus nephritis have distinct immunologic differences that may reflect the unique pathophysiological processes contributing to disease manifestations.
基金This work was supported by a grant from Shanghai Scientific Technologi cal Committee(No 954119005).
文摘To evaluate apoptosis in lupus nephritis and the relationship between the existence of apoptotic cells in renal tissue and histopathological or clinical changes Methods Apoptosis was detected by in situ nick end labeling techniques (TUNEL) in renal biopsies from 25 patients with type Ⅳ lupus nephritis (LN), 12 patients with IgA nephropathy IgAN, 4 patients with idiopathic mesangioproliferative glomerulonephritis (MsPGN) and 3 patients with acute poststreptococcal glomerulonephritis (APGN) Normal renal tissue obtained at nephrectomy for hypernephroma in 4 adults was used as control Proliferating cells were identified by proliferating cell nuclear antigen (PCNA) in these patients Results Compared to other proliferative glomerulo^nephritis and controls, the patients with lupus nephritis had less apoptotic cells, a higher ratio of PCNA+ cells/TdT+ cells (P/T) in renal tissues; and their P/T ratio in glomeruli and tubulointerstitium correlated with the chronicity index, r =0 4983 ( P =0 0132), r =0 8399 ( P <0 001), r =0 6614 ( P =0 0033), respectively P/T ratios in the glomerulus and tubule had a positive correlation with 24 hour urinary protein, r =0 8554 ( P <0 001) and r =0 7134 ( P =0 001); and a negative correlation with creatinine clearance (Ccr), r =-0 4880 ( P =0 0133) and r =-0 7229 ( P =0 001), which in tubules positively correlated with serum creatinine (Scr), r =0 4107 ( P =0 0414) Conclusions Apoptosis is reduced in proliferative lupus nephritis Intense proliferation without a commensurate increase in apoptosis is a possible mechanism that leads to chronic progressive renal histopathological
基金Supported by Department of Education of Guangdong Province:Study of Biomarkers Discovery for Patients with Relapsed Lupus Nephritis from the Perspective of Urinary Exosomal Microrna and Analysis of the Correlation with Pathogenic Dampness(2018KQNCX051)Guangdong Provincial Hospital of Traditional Chinese Medicine:Study of Biomarkers Discovery for Patients with Relapsed Lupus Nephritis from the Perspective of Urinary Exosomal Microrna and Analysis of the Correlation with Pathogenic Dampness(YN2019QL19)State Key Laboratory of Dampness Syndrome of Chinese Medicine:Early Warning and Intervention(SZ2021ZZ3204)。
文摘OBJECTIVE:To investigate the effectiveness and safety of tripterygium glycosides(TG)tablet(雷公藤多苷片)for the treatment of Lupus nephritis(LN).METHODS:Several databases were systematically searched including Pub Med,Embase,Cochrane,Wiley,China National Knowledge Infrastructure Database,Sino Med and Wanfang Library till June 20,2020.Revman5.3 was utilized to analyze the data according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement.RESULTS:In total,8 randomized controlled trials involving 583 participants were identified.Meta-analyses showed that,compared with glucocorticoids(GC)alone,the combination with TG tablet provided a statistically significant improvement in total remission(TR)(RR=1.27,95%CI:1.08–1.50,P=0.004),complete remission(CR)(RR=1.61,95%CI:1.05–2.47,P=0.03)and C3 levels(WMD=0.27,95%CI:0.14–0.39,P<0.0001),C4 levels(WMD=0.12,95%CI:0.07–0.17,P<0.00001).No significant differences were seen in TR,CR,proteinuria,serum creatinine,C3 and C4(TR:RR=1.00,95%CI:0.87–1.16,P=0.95;CR:RR=1.10,95%CI:0.78–1.56,P=0.58;proteinuria levels:WMD=-0.06,95%CI:-0.13 to 0.01,P=0.10;serum creatinine levels:WMD=-0.01,95%CI:-7.36 to 7.35,P=1.00;C3 levels:WMD=0.01,95%CI:-0.06 to 0.07,P=0.84;C4 levels:WMD=-0.01,95%CI:-0.03 to 0.01,P=0.49)between azathioprine(AZA)/leflomit(LEF)+GC and TG tablet+GC.Adverse events(hepatic dysfunction,nausea,vomitting)showed no statistical differences between the TG tablet+GC group and the GC group.There were more new onset of irregular menstruation in the TG tablet+GC group than those in the AZA+GC(RR=3.57,95%CI:1.40–9.11,P=0.008)/LEF+GC(RR=6.69,95%CI:2.42-18.46,P=0.0002)group,but leucopenia lower than those in AZA+GC group(RR=0.38,95%CI:0.17-0.85,P=0.02)and alopecia(RR=0.14,95%CI:0.03-0.77,P=0.02)and rash(RR=0.09,95%CI:0.01-0.69,P=0.02)lower than those in LEF+GC group.Conclusions:This review indicates that TG tablet maybe effective in LN treatment.Nevertheless,adverse events cannot be ignored.Large sample,multi-center,highquality clinical studies are needed to verify the exact effects and safety of TG tablet in treatment of LN.
基金The present study was supported by the National Natural Science Foundation of China(No.81170671)Shanghai Health and Family Planning Committee Hundred Talents Program(No.2018BR37).
文摘This study aimed to evaluate the efficacy and safety of mycophenolate mofetil(MMF)or tacrolimus(TAC)compared with azathioprine(AZA)as maintenance therapy for active lupus nephritis(ALN).Patients with ALN who responded to 24 weeks of induction treatment were enrolled.Patients who received MMF or TAC as induction therapy continued MMF or TAC treatment during the maintenance period,whereas those who received intravenous cyclophosphamide were subjected to AZA treatment.The primary endpoint was the incidence of renal relapse.Secondary endpoints included extrarenal flares and composite endpoints(deaths,end-stage renal disease,or doubling of serum creatinine levels).A total of 123 ALN patients(47 in the MMF group,37 in the TAC group,and 39 in the AZA group)were enrolled.The median follow-up time was 60 months.Ten MMF-treated patients,ten TAC-treated patients,and eight AZA-treated patients experienced renal relapses(P=0.844).The cumulative renal relapse rates in the MMF group(P=0.934)and TAC group(P=0.673)were similar to the renal relapse rate in the AZA group.No significant difference in the incidence of severe adverse event was observed among the groups.Long-term maintenance therapies with MMF or TAC might have similarly low rates of renal relapse and similar safety profiles compared with AZA.
基金supported by the Natural Science Foundation of Sichuan Province (Grant No.2022NSFSC1415)the Special Project of Sichuan Province Traditional Chinese Medicine Administration (Grant No. 2020JC0124)+1 种基金the Management Project of General Hospital of Western Theater Command (Grants No. 2021-XZYG-C22 and 2021-XZYG-C21)the Spark Young Innovative Talent Project of General Hospital of Western Theater Command。
文摘Lupus nephritis(LN) has a high incidence in systemic lupus erythematosus(SLE) patients, but there is a lack of sensitive predictive markers. The purpose of the study was to investigate the association between the CD4^(+)CD8^(+)double positive T(DPT) lymphocytes and LN. The study included patients with SLE without renal impairment(SLE-NRI), LN, nephritic syndrome(NS), or nephritis. Peripheral blood lymphocyte subsets were analyzed by flow cytometry. Biochemical measurements were performed with peripheral blood in accordance with the recommendations proposed by the National Center for Clinical Laboratories. The proportions of DPT cells in the LN group were significantly higher than that in the SLE-NRI group(t=4.012, P<0.001), NS group(t=3.240,P=0.001), and nephritis group(t=2.57, P=0.011). In the LN group, the risk of renal impairment increased significantly in a DPT cells proportion-dependent manner. The risk of LN was 5.136 times(95% confidence interval, 2.115–12.473) higher in cases with a high proportion of DPT cells than those whose proportion of DPT cells within the normal range. These findings indicated that the proportion of DPT cells could be a potential marker to evaluate LN susceptibility, and the interference of NS and nephritis could be effectively excluded when assessing the risk of renal impairment during SLE with DPT cell proportion.
文摘Background:Systemic lupus erythematosus(SLE)is a complex chronic autoimmune disease with no known cure.However,the regulatory mechanism of immunity-related genes is not fully understood in SLE.In order to explore new therapeutic targets,we used bioinformatical methods to analyze a series of data.Methods:After downloading and processing the data from Gene Expression Omnibus database,the differentially expressed genes of SLE were analyzed.CIBERSORT algorithm was used to analyze the immune infiltration of SLE.Based on single-cell RNA-sequencing data,the role of immune-related genes in SLE and its target organ(kidney)were analyzed.Key transcription factors affecting immune-related genes were identified.Cell-cell communication networks in SLE were analyzed.Results:In total,15 hub genes and 4 transcription factors were found in the bulk data.Monocytes and macrophages in GSE81622(SLE)showed more infiltration.There were four cell types were annotated in scRNA sequencing dataset(GSE135779),as follows T cells,monocyte,NK cells and B cells.Immunity-related genes were overexpressed in monocytes.Conclusion:The present study shows that immune-related genes affect SLE through monocytes and play an important role in target organ renal injury.
