Changes in macrophage infiltration and podocyte injury in lupus nephritis patients with repeated renal biopsy: Report of three cases

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.

Advances in Diagnosis and Treatment of Lupus Nephritis(Class V)

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.

Association of C-reactive protein and complement factor H gene polymorphisms with risk of lupus nephritis in Chinese population

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.

Network pharmacology and data analysis method to explore the traditional Chinese medicine regulates ferroptosis key genes in the occurrence and prognosis of lupus nephritis

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.

Effect of Rituximab Versus Mycophenolate Mofetil or Cyclophosphamide as Control in Lupus Nephritis:A Meta-Analysis

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.

Dan Bai Xiao Formula combined with glucocorticoids and cyclophosphamide for pediatric lupus nephritis:A pilot prospective study

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.

Alport syndrome combined with lupus nephritis in a Chinese family:A case report

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.

Pneumothorax during retroperitoneal laparoscopic partial nephrectomy in a lupus nephritis patient:A case report

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.

Outcome of Leflunomide in the Treatment of Proliferative Lupus Nephritis Compared to Cyclophosphamide

Background: 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. Objective: To evaluate the outcome of leflunomide in the treatment of proliferative lupus nephritis compared to cyclophosphamide. Method: 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. Result: 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). Conclusion: 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.

Lupus Nephritis Class II: A Challenging Entity

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.

Infectious Complications in Lupus Nephritis and Associated Factors: A Multicenter Study

Introduction: 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. Patients and method: 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. Results: 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 Escherichia coli (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). Conclusion: Infections were common during lupus nephritis. The presence of a proliferative class was risk factors for infection.

A Case Report of Lupus Panniculitis in a Hemodialysis Patient with Lupus Nephritis

Background: Systemic lupus erythematosus and lupus nephritis are relatively common autoimmune diseases that can cause damage to multiple systems. Aim: To investigate the lupus activity of patients with lupus nephritis on hemodialysis and the combined occurrence of lupus panniculitis. Case introduction: 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. Conclusion: 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.

Targeted therapies for lupus nephritis:Current perspectives and future directions

Lupus nephritis(LN),a severe manifestation of systemic lupus erythematosus,poses a substantial risk of progression to end-stage renal disease,with increased mortality.Conventional therapy for LN relies on broad-spectrum immunosuppressants such as glucocorticoids,mycophenolate mofetil,and calcineurin inhibitors.Although therapeutic regimens have evolved over the years,they have inherent limitations,including non-specific targeting,substantial adverse effects,high relapse rates,and prolonged maintenance and remission courses.These drawbacks underscore the need for targeted therapeutic strategies for LN.Recent advancements in our understanding of LN pathogenesis have led to the identification of novel therapeutic targets and the emergence of biological agents and small-molecule inhibitors with improved specificity and reduced toxicity.This review provides an overview of the current evidence on targeted therapies for LN,elucidates the biological mechanisms of responses and failure,highlights the challenges ahead,and outlines strategies for subsequent clinical trials and integrated immunomodulatory approaches.

B1-cell-produced anti-phosphatidylserine antibodies contribute to lupus nephritis development via TLR-mediated Syk activation

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.

Podocyte injury and death:New insights into lupus nephritis pathogenesis and therapy

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.

Immunophenotyping identifies distinct cellular signatures for systemic lupus erythematosus and lupus nephritis

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.

IL-17 induces autoantibody overproduction and peripheral blood mononuclear cell overexpression of IL-6 in lupus nephritis patients

To investigate the role of IL-17 in the overproduction of autoantibodies and IL-6 overexpression by peripheral blood mononuclear cells (PBMC) of lupus nephritis (LN) patients Methods Fifteen consecutively hospitalized LN patients were selected as subjects and 15 healthy adults as normal controls PBMC were obtained by Ficoll density gradient centrifugation IgG, anti-dsDNA antibody and IL-6 protein levels were assessed using enzyme-linked immunosorbent assays (ELISA) on the supernatant of cul tured PBMC of LN patients or normal controls IL-6 mRNA levels in PBMC were measured using reverse transcription-polymerase chain reaction (RT-PCR) Results In medium culture, IgG, anti-dsDNA and IL-6 protein levels of the supernatant of PBMC from LN patients were significantly higher than those from normal controls (1492 1±73 2 ng/ml vs 636 7±51 9 ng/ml for IgG, 306 6±53 7 IU/ml vs 95 8±11 6 IU/ml for anti-dsDNA and 50 92±15 92 ng/ml vs 1 77±0 73 ng/ml for IL-6, all P<0 001) In LN patients, IgG, anti-dsDNA and IL-6 protein levels were higher in the supernatants of PBMC in the IL-17-stimulated culture than the medium culture, but in normal controls, only the IL-6 protein levels were significantly higher The increase in IgG, anti-dsDNA and IL-6 protein levels induced by IL-17 was dose-dependent and could be completely blocked by IL-17 monoclonal antibody mIgG 28 and partially blocked by dexamethasone Similarly, IL-6 mRNA overexpression of PBMC in LN patients or normal controls induced by IL-17 was both dose- and time-dependent During medium culture, IL-6 mRNA levels in LN patients were significantly higher than those in normal controls (1 80±0 11 vs 0 36±0 07) During stimulation with IL-17, IL-6 mRNA levels in LN patients were higher than those in normal controls (3 21±0 24 vs 1 30±0 14, P<0 05) and also significantly higher when comparing the stimulated culture with the medium culture either in LN patients or normal control Conclusions IL-17 may play an important role in the pathogenesis of LN through the induction of IgG, anti-dsDNA overproduction and IL-6 overexpression of PBMC in LN patients

Imbalance of Interleukin 18 and Interleukin 18 Binding Protein in Patients with Lupus Nephritis

To evaluate the balance status of interleukin 18 （IL-18） and interleukin 18 binding protein （IL-18BP） in circulation in patients with lupus nephritis （LN） and primary nephrotic syndrome （PNS）, plasma levels as well as mRNA expression in peripheral blood mononuclear cells （PBMCs） of IL-18 and IL-18BP were measured by ELISA and RT-PCR respectively. The ratio of IL-18/IL-18BP was also calculated. Both plasma IL-18 and IL-18BP increased significantly in LN patients while only IL-18BP increased in PNS, which resulted in an elevated ratio of IL-18/IL-18BP in LN but not in PNS patients when compared with normal controls. In contrast, increased level of IL-18 mRNA was only detected in LN but not in PNS group, although IL-18BP mRNA expressions in PBMCs in both groups were higher than that in control. The imbalance of IL-18 and IL-18BP might be involved in the pathogenesis of LN, based on which a therapeutic approach is valuable to be developed for LN.

Effect of Artemisinin Combined with Glucocorticoid on the Expressions of Glucocorticoid Receptor α mRNA,Glucocorticoid Receptor β mRNA and P300/CBP Protein in Lupus Nephritis Mice

Objective：To investigate the therapeutic effects and mechanisms of using artemisinin（Art） combined with glucocorticoid（GC） to treat lupus nephritis（LN） mice.Methods：Forty hybrid female mice were randomly and equally divided into four groups with the method of random number table：control group,model group,prednisone group administrated with 6.45 mg/（kg·d） prednisone suspension,and Art＋prednisone group administrated with 150 mg/（kg·d） Art suspension and 3.225 mg/（kg·d） prednisone suspension.A mice model of LN was established by injection with living lymph cell suspension.The changes of urine protein/24h,the expressions of GC receptorα（GRα） mRNA,GC receptorβ（GRβ） mRNA in peripheral blood mononuclear cells（PBMCs）,and transcriptional coactivator P300/CBP protein in renal tissue were measured.Results： Compared with the model group,the treatment groups had significant decrease in urine protein/24 h,and renal pathological lesion（P0.01）.In the same groups,the expression of transcriptional coactivator P300/CBP protein in renal tissue and GRαmRNA were significantly increased,and GRβmRNA expression was significantly decreased（P0.01）.And the Art＋prednisone group has a better therapeutic effect than the prednisone group （P0.01）.Conclusions：Art has therapeutic sensitization effects on GC in the LN mice.The underlying mechanism could be correlated with the effect of Art on the increase of the expressions of GRαmRNA and transcriptional coactivator P300/CBP protein in renal tissue and on the decrease of the expression of GRβmRNA in PBMCs.

Mizoribine versus mycophenolate mofetil or intravenous cyclophosphamide for induction treatment of active lupus nephritis

Background Lupus nephritis （LN） is one of the most serious manifestations of systemic lupus erythematosus.Although there have been substantial improvements in LN treatment over the last decade,the outcome remains unoptimistic in a considerable percentage of patients.The aim of this study was to evaluate the efficacy and safety of mizoribine （MZR）,a novel selective inhibitor of inosine monophosphate dehydrogenase,as induction treatment for active LN in comparison with mycophenolate mofetil （MMF） and intravenous cyclophosphamide （CYC）.Methods Ninety patients with active LN were observed.Thirty patients were given MZR orally at the dose of 300 mg every other day.Thirty patients took MMF at 2 g per day in two divided doses.Thirty patients received CYC intravenously 0.5 g every 2 weeks.Therapeutic effects and adverse events （AEs） were evaluated at the end of 24-week treatment.Oneway analysis of variance （ANOVA） followed by Dunn＇s test was applied to compare the difference among the groups.For comparing categorical data between two groups,χ^2 test was employed.Results Early responses at week 12 were achieved by 73.3%,90.0%,and 96.7% in MZR,MMF,and CYC groups,respectively.There was no significant difference in the complete remission rates （22.7%,24.0%,and 25.0%,respectively） or overall response rates （68.2%,72.0%,and 75.0%,respectively） among the three groups at week 24.The most prominent drop-down of Systemic Lupus Erythematosus Disease Activity Index scores was observed in MMF or CYC group,and the decline of health assessment questionnaire scores in MZR or MMF group was more prominent than that in the CYC group at week 12.Serum complement 3 （C3） or C4 levels were elevated in all groups after the treatments.CYC was more effective in inhibiting anti-double-stranded DNA antibody,while MZR was more effective in inhibiting antinuclear antibody.The incidences of AEs in patients treated with CYC were significantly higher than those in patients treated with MZR or MMF （24.2% for CYC vs.3.3% for MZR,and 2.6% for MMF,P=0.01）.Conclusions MZR is well tolerated and has an effect similar to MMF in the induction therapy of active LN.MZR may serve as an alternative approach for LN patients.