BCD020 rituximab bioanalog compared to standard treatment in juvenile systemic lupus erythematosus: The data of 12 months casecontrol study

BACKGROUND Systemic lupus erythematosus(SLE)is the most frequent and serious systemic connective tissue disease.Nowadays there is no clear guidance on its treatment in childhood.There are a lot of negative effects of standard-of-care treatment(SOCT),including steroid toxicity.Rituximab(RTX)is the biological B-lymphocyte-depleting agent suggested as a basic therapy in pediatric SLE.AIM To compare the benefits of RTX above SOCT.METHODS The data from case histories of 79 children from the Saint-Petersburg State Pediatric Medical University from 2012 to 2022 years,were analyzed.The diagnosis of SLE was established with SLICC criteria.We compared the outcomes of treatment of SLE in children treated with and without RTX.Laboratory data,doses of glucocorticosteroids,disease activity measured with SELENA-SLEDAI,RESULTS Patients,treated with RTX initially had a higher degree of disease activity with prevalence of central nervous system and kidney involvement,compared to patients with SOCT.One year later the disease characteristics became similar between groups with a more marked reduction of disease activity(SELENA-SLEDAI activity index)in the children who received RTX[-19 points(17;23)since baseline]compared to children with SOCT[-10(5;15.5)points since baseline,P=0.001],the number of patients with active lupus nephritis,and daily proteinuria.During RTX therapy,infectious diseases had three patients;one patient developed a bi-cytopenia.CONCLUSION RTX can be considered as the option in the treatment of severe forms of SLE,due to its ability to arrest disease activity compared to SOCT.

Impact of systemic steroids combined with immunosuppressive treatment on glaucomatous features in patients with systemic lupus erythematosus

AIM:To evaluate the incidence of increased intraocular pressure(IOP)and glaucomatous changes in systemic lupus erythematosus(SLE)patients in comparison with systemic steroids and immunosuppressive treatment.METHODS:Sixty-two women with SLE were divided into two groups:treated(n=47,94 eyes)and not treated(n=15,30 eyes)with systemic glucocorticosteroids(GC;GC-free).Twenty-one individuals in GC group were treated with immunosuppressive agents(immunomodulating and biologic).The visual acuity and IOP with ocular pulsatile amplitude(OPA)measurements,as well as scanning laser polarimetry(GDx)with nerve fiber index(NFI)measurement,spectral domain optical coherence tomography(SD-OCT)of the optic disk with retinal nerve fiber layer(RNFL)analysis and the macular region with ganglion cell analysis(GCA)were performed.RESULTS:Mean IOP values in group with combined GC and immunosuppressive therapy was 15.8±2.56 mm Hg and was significantly lower than in individuals with exclusive GC treatment(17.63±4.38 mm Hg,P=0.043).Contrary,no dif ferences in mean IOP values between GC-free group and individuals treated with combined GC and immunosuppressive therapy were detected(P=0.563).Similarly,mean IOP in GC was 17.14±3.94 mm Hg and in GC-free patients was equal to 16.67±3.45 mm Hg(P=0.671).According to treatment regimen no statistical differences in optic disk SD-OCT for RNFL thickness,RNFL symmetry,cupping volume and the C/D ratio were observed.Similarly,no statistical differences for the mean and minimal ganglion cell layer(GCL)thickness measured in macular SD-OCT or NFI in GDx were detected.CONCLUSION:Combined immunosuppressive and systemic GC therapy in SLE patients may lower the risk of iatrogenic ocular hypertension.No relationship between treatment regimen and glaucomatous damage of optic nerve fibers in analyzed groups with SLE is detected.

A rationally designed CD19 monoclonal antibody-triptolide conjugate for the treatment of systemic lupus erythematosus

Tripterygium wilfordii Hook F(TWHF)is a traditional Chinese medicine widely used in the treatment of systemic lupus erythematosus(SLE),with triptolide(TP)as its main active ingredient.However,its side effects also induced by TP,especially hepatotoxicity and reproductive toxicity,largely limit its application in a subset of patients.Monoclonal antibodies(mAbs)developed for the treatment of SLE that deplete B cells by targeting B cell-expressing antigens,such as CD19,have failed in clinical trials,partly due to their poor efficacy in consuming B cells.Here,we report the development of a rationally designed antibody‒drug conjugate(ADC),CD19 mAb-TP conjugate,to alleviate the side effects of TWHF and simultaneously improve the therapeutic efficacy of CD19 mAb.The CD19 mAb-TP conjugate,which was named ADC-TP,selectively depleted B cell subsets both in vitro and in vivo and effectively alleviated disease symptoms in mouse lupus models with enhanced therapeutic efficacy than CD19 mAb and fewer side effects than TP.Our present study proposes a CD19 mAb‒TP conjugate strategy to mitigate the toxicity of TWHF while also enhancing the therapeutical efficacy of CD19 mAbs for the treatment of SLE,providing a feasible method for improving the current agents used for treating SLE.

Unveiling the nexus:Decoding interactions between regulated cell death and systemic lupus erythematosus pathogenesis for innovative therapeutic avenues

Systemic lupus erythematosus(SLE)is characterized by disruptions in cell death pathways and impaired clearance of apoptotic cells,resulting in immune dysregulation and tissue damage.This review explores the complex interplay of regulated cell death(RCD)mechanisms,including apoptosis,necroptosis,pyroptosis,NETosis,autophagy,and ferroptosis,in the pathogenesis of SLE.These pathways release autoantigens and danger signals,triggering autoimmune reactions and inflammation.Six various RCDs have mutual associates to support immune dysregulation and are associated with SLE.Apoptosis intrinsically induces immune tolerance by packaging dying cells into immunologically inert fragments.Deficiencies in apoptotic clearance will result in impaired tolerance.Necroptosis,pyroptosis,NETosis,and ferroptosis lead to cell membrane destruction,production of intracellular immunostimulatory components,and triggering a strong inflammatory immune reaction.Abnormal autophagic activity affects the development,differentiation,function,and metabolism of many immune cell subpopulations.Investigating the interconnections between cell death pathways and SLE sheds light on the disease's underlying mechanisms and provides opportunities for novel therapeutic interventions.The convergence of precision medicine and innovative strategies targeting these intricate pathways holds promise for expanding the landscape of SLE treatment.

B-cell-targeted therapies in systemic lupus erythematosus

Autoreactive B cells are one of the key immune cells that have been implicated in the pathogenesis of systemic lupus erythematosus （SLE）. In addition to the production of harmful auto-antibodies （auto-Abs）, B cells prime autoreactive T cells as antigen-presenting cells and secrete a wide range of pro-inflammatory cytokines that have both autocrine and paracrine effects. Agents that modulate B cells may therefore be of potential therapeutic value. Current strategies include targeting B-cell surface antigens, cytokines that promote B-cell growth and functions, and B- and T-cell interactions. In this article, we review the role of B cells in SLE in animal and human studies, and we examine previous reports that support B-cell modulation as a promising strategy for the treatment of this condition. In addition, we present an update on the clinical trials that have evaluated the therapeutic efficacy and safety of agents that antagonize CD20, CD22 and B-lymphocyte stimulator （BLyS） in human SLE. While the results of many of these studies remain inconclusive, belimumab, a human monoclonal antibody against BLyS, has shown promise and has recently been approved by the US Food and Drug Administration as an indicated therapy for patients with mild to moderate SLE. Undoubtedly, advances in B-cell immunology will continue to lead us to a better understanding of SLE pathogenesis and the development of novel specific therapies that target B cells.

B cells biology in systemic lupus erythematosus—from bench to bedside

Systemic lupus erythematosus(SLE) is a debilitating autoimmune disease that can involve multi-organs. B cells play a central role in the immunopathogenesis via antibody-dependent and antibody-independent ways. Excessive autoantibodies production, hyperresponsiveness and prolonged survival of autoreactive B cells are characteristics of SLE. In this article, mechanisms of self-tolerance loss of B cells and promising B cell-targeting therapies in lupus are reviewed and discussed.

Effect of Detoxification,Removing Stasis and Nourishing Yin Method on Corticosteroid-induced Hyperlipidemia in Patients with Systemic Lupus Erythematosus

Objective： To observe the effect of TCM therapy for detoxification, removing stasis, and nourishing yin on corticosteroid-induced hyperlipemia in patients with systemic lupus erythematosus （SLE）, and to investigate its mechanism. Methods： One hundred and seventy patients with SLE were randomly assigned to the integrative medicine group （IM group） and the Western medicine group （WM group）, 85 in each group. Also, 30 healthy subjects selected from blood donors were enrolled in the normal control （NC） group. All patients were treated mainly with prednisone, while those in the IM group were given TCM therapy additionally, and the therapeutic course for both groups was 6 successive months. The changes of serum total cholesterol （TC）, triglyceride （TG）, high density lipoprotein cholesterol （HDL-C）, low density lipoprotein cholesterol （LDL-C）, very low density lipoprotein cholesterol （VLDL-C） and apolipoprotein A （ApoA） were determined and observed. A 2-year follow-up study was carried out in 16 patients of the WM group and 25 of the IM group. Results： Before treatment, no significant difference had been found among the three groups in the serum levels of lipids and lipoproteins. After the 6-month treatment, as compared with the WM group, the IM group showed lower levels of TC, TG, LDL-C, and VLDL-C （P〈0.05 or P〈0.01） and higher levels of HDL-C and ApoA （P〈0.05）. A similar effect was also shown by the follow-up study in the IM group （P〈0.05 or P〈0.01）. Conclusion： TCM therapy for detoxification, removing stasis, and nourishing yin can effectively regulate the levels of serum lipids and lipoproteins in preventing and treating SLE patients with corticosteroid-induced hyperlipemia.

Phenotypic characterization of patients with activated PI3Kδ syndrome 1 presenting with features of systemic lupus erythematosus

Activated phosphoinositide 3-kinase d syndrome 1(APDS1)is a primary immunode-ficiency disease caused by gain-of-function mutations in PIK3CD.Clinical features of autoimmune disease have been reported in patients with APDS1.In this study,we reported three patients with APDS1 presenting with systemic lupus erythematosus(SLE)phenotype.The clinical manifestations included recurrent respiratory tract infection,lymphoproliferation,Coombs-positive hemolytic anemia,decreased complement fractions,positive antinuclear antibodies,renal complications related to SLE associated diseases,which met the clinical spectrum of APDS1 and the classification criteria of SLE.The immunological phenotype included an inversion in the CD4:CD8 ratio,an increase in both non-circulating Tfh CD4^(+)memory T and circulating Tfh populations,a low level of recent thymic emigrant T cells,overexpression of CD57 on T cells,and a decrease in B cells with fewer antibody class switch recombination.These phenotypes detected in patients with APDS1 presenting with SLE were resemble that in patients with APDS1 presenting without SLE.Meanwhile,we described the effect of glucocorticoids and rapamycin therapy on patients with APDS1.The phosphorylation of S6 at Ser235/236 was inhibited in patients with APDS1 who underwent glucocorticoids therapy,including two who presented with SLE phenotype.The phosphorylation of AKT at Ser473 and phosphorylation of S6 at Ser235/236 were inhibited in other patients with APDS1 who underwent rapamycin therapy.Here,we showed the coexistence of immunodeficiency and SLE phenotype in APDS1,and the inhibition of rapamycin in activated Akt-mTOR signaling pathway.

Surgery and antibiotics for the treatment of lupus nephritis with cerebral abscesses:A case report

BACKGROUND Systemic lupus erythematosus(SLE)patients are extremely susceptible to opportunistic infections due to glucocorticoid and immunosuppressive treatments,which often occur in the respiratory system,the urinary system and the skin.However,multiple cerebral infections are rarely reported and their treatment is not standardized,especially when induced by a rare pathogen.CASE SUMMARY A 46-year-old woman was treated with glucocorticoid and immunosuppressant for SLE involving the hematologic system and kidneys(class IV-G lupus nephritis)for more than one year.She was admitted to hospital due to headache and fever,and was diagnosed with multiple cerebral abscesses.Brain enhanced magnetic resonance imaging showed multiple nodular abnormal signals in both frontal lobes,left parietal and temporal lobes,left masseteric space(left temporalis and masseter region).The initial surgical plan was only to remove the large abscesses in the left parietal lobe and right frontal lobe.After surgery,based on the drug susceptibility test results(a rare pathogen Nocardia asteroides was found)and taking into consideration the patient’s renal dysfunction,a multi-antibiotic regimen was selected for the treatment.The immunosuppressant mycophenolate mofetil was discontinued on admission and the dose of prednisone was reduced from 20 mg/d to 10 mg/d.Re-examination at 3 mo post-surgery showed that the intracranial lesions were reduced,the edema around the lesions was absorbed and dissipated,and her neurological symptoms had disappeared.The patient had no headaches or other neurological symptoms and lupus nephritis was stable during the 2-year follow-up period.CONCLUSION In this report,we provide reasonable indications for immunosuppression,anti-infective therapy and individualized surgery for an SLE patient complicated with multiple cerebral abscesses caused by a rare pathogen,which may help improve the diagnosis and treatment of similar cases.

中医药治疗系统性红斑狼疮的研究进展

中医药治疗系统性红斑狼疮的方法如分证论治、分期论治、经典方剂、中成药及自拟方等,可明显改善系统性红斑狼疮患者临床症状与体征,疗效显著,不良反应少。该文采用文献检索,归纳近年来中医药治疗系统性红斑狼疮及其系统病变的研究进展,为中医药更好地治疗系统性红斑狼疮及其全身病变提供参考。

系统性红斑狼疮患者应用靶向B细胞治疗后发生中枢神经系统病变文献病例分析

目的探讨系统性红斑狼疮(SLE)患者经靶向B淋巴细胞生物制剂治疗后发生中枢神经系统不良反应的临床特征。方法检索国内外相关数据库(截至2023年5月),收集系统性红斑狼疮患者经贝利尤单抗、利妥昔单抗治疗后发生中枢神经系统病变的病例报告类文献,提取患者的基本信息、贝利尤单抗或利妥昔单抗用药情况(用法用量、单用或联用、联用方案等)、中枢神经系统病变发生时间、临床表现、影像学特征、临床治疗及转归等,并进行描述统计分析。结果检索到进行性多灶性脑白质病(PML)患者14例,发病年龄(50.71±11.45)岁;可逆性后部脑病综合征(PRES)患者24例,发病年龄(30.67±14.93)岁。纳入有详细病例报道的患者共7例,7例患者均未合并HIV感染、恶性肿瘤及其他自身免疫性疾病。7例患者均经磁共振检查确诊,均未行脑组织活检。临床表现:癫痫5例,视物模糊或视力丧失3例,构音障碍或失语2例,头痛2例,昏迷1例,血压升高4例。最终7例患者中1例死亡。结论应用靶向B细胞治疗后,SLE患者中枢神经系统副作用多发生在疾病活动期且合并使用其他免疫抑制剂时。患者的临床表现容易与神经精神狼疮混淆,导致病情延误,提示在使用靶向B细胞生物制剂治疗时,应评估SLE患者发生中枢神经系统副作用的潜在风险。

狼疮肾炎靶向B细胞治疗研究新进展

狼疮肾炎(lupus nephritis,LN)是系统性红斑狼疮严重的并发症之一,也是中国常见的继发性肾小球肾炎。目前临床上无法治愈LN,只能通过激素联合免疫抑制剂来缓解症状,延缓肾功能衰退。然而现有的治疗方案对LN的完全肾脏缓解率偏低,而且疾病容易复发。近年来,随着LN发病机制的深入研究,以B细胞为靶点的各种生物制剂、治疗手段以及抗细胞因子活化的生物制剂不断被研发。因此,本文就目前靶向生物制剂和治疗手段在LN的临床研究现状做一综述,旨在为临床医生提供治疗新思路。

克罗恩病合并系统性红斑狼疮1例

克罗恩病(Crohn′s disease,CD)合并系统性红斑狼疮(systemic lupus erythematosus,SLE)临床上十分少见,患者的临床表现和治疗手段均与普通CD有所不同。本文报告1例CD合并SLE病例,介绍其临床表现和诊疗经过,以期为临床医师提供参考。

系统性红斑狼疮CAR T细胞治疗疗效预测及安全性评估的潜在生物标志物

系统性红斑狼疮(systemic lupus erythematosus,SLE)是一种复杂的自身免疫疾病,传统治疗在部分重度和难治性患者中效果有限。近期研究显示,嵌合抗原受体(chimeric antigen receptor,CAR)T细胞疗法在SLE治疗中展现出了具有前景的疗效。生物标志物在精准评估治疗效果和安全性方面至关重要,CAR T细胞治疗与安全性评估标志物包括传统标志物和与CAR T细胞疗法相关的标志物。传统的SLE病情监测标志物,仍可用于CAR T细胞治疗基线随访和病情监测,如血清抗双链DNA、抗单链DNA和抗核小体等自身抗体的滴度下降,血清补体水平恢复正常,以及尿蛋白/肌酐比值的改善,均提示病情得到有效控制。CAR T细胞疗效监测标志物分为B细胞和T细胞标志物。输注后,B细胞数量下降,B细胞表型以初始B细胞为主,记忆B细胞和浆母细胞的比例显著降低,表明治疗取得了疗效。输注前,初始T细胞(CD45RA+CD27+)和中央记忆型T细胞(CD45RA-CD62L+CD27+)的高比例则提示更强的抗肿瘤效应;患者的CAR T细胞表达与早期记忆分化相关的转录因子,如T细胞因子7和淋巴增强子结合因子1,提示这些患者对CAR T细胞疗法更为敏感。输注后,CD25、CD69和CD137等T细胞激活标志物,以及CD57、PD-1和Tim-3等耗竭标志物的高表达,提示T细胞的杀伤能力受到限制。CAR T细胞治疗安全性标志物不仅包括CAR T细胞分泌的效应细胞因子(如白细胞介素-2和IFN-γ),还包括单核细胞和巨噬细胞产生的细胞因子(如IL-1和IL-8),其水平可用于评估CAR T细胞疗法最常见的毒副反应[细胞因子释放综合征(cytokine release syndrome,CRS)和免疫效应细胞相关神经毒性综合征(immune effector cell-associated neurotoxicity syndrome,ICANS)]。高水平的血清巨噬细胞炎性蛋白1α对于预测CAR T细胞治疗后发生严重CRS和ICANS的风险具有较高的价值。此外,基线血小板计数和中性粒细胞绝对值可预测血液毒性,由IL-8、IFN-γ和IL-1β组成的感染相关预测模型,能够有效预测患者输注后出现严重感染的风险。CAR受体结构设计、清除淋巴细胞的化疗方式,患者曾接受的治疗选择及自身免疫状态等都会影响CAR T细胞治疗的疗效及安全性。在当前及未来将开启的相关临床研究中,应纳入全面、规范的检测和评估体系,为CAR T细胞疗法在SLE等自身免疫疾病的应用,提供比较标准。

cGAS-STING信号通路在系统性红斑狼疮中的研究进展

cGAS-STING信号通路在免疫反应调控中发挥着至关重要的作用,其通过感知细胞质内DNA的存在,激活下游一系列分子,导致Ⅰ型干扰素等炎症细胞因子的释放,最终参与和调控免疫反应的发生。SLE发病机制复杂,免疫功能紊乱及Ⅰ型干扰素等细胞因子参与SLE的发生发展。本文将就cGAS-STING信号通路在SLE中的研究进展进行综述,以期为SLE的诊断及靶向治疗提供新方向。

阶段性正念减压疗法联合八段锦对系统性红斑狼疮患者自尊水平及自护能力的影响

目的探究阶段性正念减压疗法联合八段锦对系统性红斑狼疮(Systemic Lupus Erythematosus,SLE)患者自尊水平及自护能力的影响。方法选取2021年7月—2023年6月梧州市工人医院收治的120例系统性红斑狼疮患者作为研究对象。采用不同的护理模式分为对照组和干预组,每组60例。对照组实施常规护理模式,干预组实施阶段性正念减压疗法联合八段锦护理模式,两组患者在干预前、干预3个月、6个月分别采用自尊水平量表(Self-esteem Scale,SES)、日常生活活动能力(Activities of Daily Living,ADL)量表、系统性红斑狼疮疾病活动度量表(Systemic Lupus Erythematosus Disease Activity Index,SLEDAI)进行总体康复效果评定。结果干预3个月、6个月后,两组患者SES评分、ADL评分明显上升,SLEDAI评分明显下降;干预6个月后,干预组SES评分(34.83±2.93)分、ADL评分(89.58±13.60)分显著高于对照组,SLEDAI评分(2.77±2.19)分低于对照组,差异有统计学意义(t=4.765、3.442、3.576,P均<0.05)。结论正念减压疗法联合八段锦增强了SLE患者自信心及自我护理能力。

针灸联合健脾滋肾汤治疗系统性红斑狼疮临床观察

目的 探讨针灸联合健脾滋肾汤治疗系统性红斑狼疮的效果。方法 回顾性分析于都县中医院于2020年6月—2022年6月收治的66例系统性红斑狼疮患者,以治疗方案的不同作为分组依据,将32例采用常规西药(泼尼松+硫酸羟氯喹)治疗的患者纳入常规组,34例应用常规治疗+针灸联合健脾滋肾汤治疗的患者则归为研究组。治疗3个月后,比较两组C反应蛋白(CRP)、红细胞沉降率(ESR)以及补体C_(3)、C_(4)水平,同时对比中医证候积分,对临床疗效开展评估。结果 治疗后,研究组CRP、ESR水平低于常规组,补体C_(3)、C_(4)水平高于常规组(P<0.05);研究组高热面赤、斑疹鲜红、肌肉关节酸痛评分均较常规组低(P<0.05)。研究组治疗总有效率为97.06%(33/34),高于常规组的81.25%(26/32)(P<0.05)。结论 针灸联合健脾滋肾汤治疗系统性红斑狼疮,可实现生化指标的改善,有助于缓解机体炎症状态,改善免疫功能,对中医证候积分的降低有重要意义,效果确切。

营养治疗对超重/肥胖系统性红斑狼疮患儿体成分的影响

目的 探讨营养治疗对正在应用激素治疗的超重/肥胖系统性红斑狼疮(systemic lupus erythematosus,SLE)患儿体成分的影响。方法 招募2018年12月至2022年6月北京儿童医院应用糖皮质激素(glucocorticoid,GC)治疗的7~18岁超重/肥胖SLE患儿。符合纳入、排除标准并签署知情同意书后,首先全部纳入观察组。观察组给予营养治疗,能量目标为身高对应50百分位数年龄的轻度体力活动推荐摄入量的基础上减少10%;随访24周后,为防止患儿间信息交流对研究的影响,暂中断入组6个月以上。后续按照纳入、排除标准继续完成对照组入组,对照组给予营养教育。各组均在入组后4、12、24周进行门诊随访,主要监测指标:人体学测量、实验室检查,并记录糖皮质激素用量。结果 最终纳入60例患儿,其中观察组40例,对照组20例。两组间基线数据(性别、年龄、体质量指数、GC用量等)差异均无统计学意义。两组患儿基线时的体脂率(body fat percentage,BFP)与内脏脂肪面积(visceral fat area,VFA)差异无统计学意义;随访12、24周后,观察组BFP和VFA均较基线时显著降低(P<0.05),对照组BFP和VFA均较基线时显著升高(P<0.05);两组患儿12、24周时GC用量均较基线显著减少(P<0.05),但两组间差异无统计学意义(P>0.05)。结论 营养治疗可改善激素治疗过程中超重/肥胖SLE患儿的体脂率和内脏脂肪面积。

Dawn of CAR-T cell therapy in autoimmune diseases

Chimeric antigen receptor(CAR)-T cell therapy has achieved remarkable success in the treatment of hematological malignancies.Based on the immunomodulatory capability of CAR-T cells,efforts have turned toward exploring their potential in treating autoimmune diseases.Bibliometric analysis of 210 records from 128 academic journals published by 372 institutions in 40 countries/regions indicates a growing number of publications on CAR-T therapy for autoimmune diseases,covering a range of subtypes such as systemic lupus erythematosus,multiple sclerosis,among others.CAR-T therapy holds promise in mitigating several shortcomings,including the indiscriminate suppression of the immune system by traditional immunosuppressants,and non-sustaining therapeutic levels of monoclonal antibodies due to inherent pharmacokinetic constraints.By persisting and proliferating in vivo,CAR-T cells can offer a tailored and precise therapeutics.This paper reviewed preclinical experiments and clinical trials involving CAR-T and CAR-related therapies in various autoimmune diseases,incorporating innovations well-studied in the field of hematological tumors,aiming to explore a safe and effective therapeutic option for relapsed/refractory autoimmune diseases.

系统性红斑狼疮:从发病机制到新型靶向治疗

系统性红斑狼疮(systemic lupus erythematosus, SLE)是一种累及多器官/系统的自身免疫性疾病,其病因复杂,涉及分子遗传、表观遗传、先天性免疫、获得性免疫、种族、激素和环境因素等多个方面。近年来,随着免疫细胞的精细分型、全基因组关联研究、单细胞测序、多组学分析、基因编辑等技术的推广应用,人们对SLE的发病机制有了越来越深入的认识,同时也推动了各种靶向免疫细胞、共刺激分子、细胞因子/信号转导通路的单克隆抗体或小分子药物以及嵌合抗原受体T细胞免疫治疗的开发及临床研究。贝利尤单抗、泰它西普、阿尼鲁单抗以及伏环孢素获批临床应用,为中重度SLE患者尤其是难治性SLE患者提供了更多选择。