Lupus-prone B6.Nba2 male and female mice display anti-DWEYS reactivity and a neuropsychiatric phenotype

ObjectiveNeuropsychiatric lupus (NPSLE), a manifestation of the autoimmune disease systemic lupus erythematosus (SLE), is characterized by psychiatric symptoms including anxiety and depression and upregulated autoantibodies. The B6.Nba2 spontaneous mouse model develops SLE, but has not previously been tested for NPSLE.MethodsWe investigated the NPSLE phenotype in male and female B6.Nba2 mice (n = 12 each) and age- and sex-matched B6 controls (n = 10 each) via behavioral assessments for anxiety, depression, and memory deficits. Serum anti-dsDNA, anti-nRNP, anti-DWEYS peptide reactive IgG autoantibody levels and soluble TWEAK levels were determined by ELISA. Hippocampal regions were stained for activated microglia and neurons.ResultsBoth male and female B6.Nba2 mice showed elevated anti-dsDNA IgG, anti-nRNP IgG and anti-DWEYS reactive antibodies, elevated serum soluble TWEAK levels, and a strong anxiety and depression phenotype (p < 0.05–0.0001). Male B6.Nba2 mice developed this phenotype at a slightly older age than females. Female B6.Nba2 mice displayed reduced numbers of neurons in the hippocampal region compared to female B6 controls (p < 0.05).ConclusionThe B6.Nba2 mouse model recapitulates many known NPSLE phenotypes, making it a promising model to investigate the development of NPSLE in the context of SLE.     

Discovering novel lung cancer associated antigens and the utilization of their autoantibodies in detection of lung cancer

ObjectiveThe identification of tumor-associated antigens (TAAs) and their corresponding autoantibodies in lung cancer (LC) may expand our vision of cancer immunity. This study aims to screen novel TAAs to distinguish LC from the healthy population.MethodsIn our previous study, 35 genes encoding LC-associated TAAs were identified from the serological analysis of recombinant cDNA expression libraries (SEREX), and Oncomine database was further used to identify potential genes in cancer progression. Autoantibody to TAAs were tested by enzyme-linked immunosorbent assay (ELISA) in sera from 1379 participants in validation set and verification set.FindingsBased on analysis of three independent microarrays in Oncomine, ten genes were consistently dysregulated in LC. The sera level and positive frequency of the anti-TOP2A, anti-ACTR3, anti-RPS6KA5 and anti-PSIP1 from LC patients were higher than normal control in validation set. The area under curve (AUC) of anti-TOP2A, anti-ACTR3, anti-RPS6KA5 and anti-PSIP1 was respectively 0.758, 0.787, 0.707, 0.668. The sensitivity of these four autoantibodies for LC detection ranged from 26.63 % to 32.07 % with the specificity over 90 %. Data from the verification set confirmed the results. Except that, the frequency of serum autoantibody against TOP2A (43.3 %) and ACTR3 (50.0 %) was significantly higher in early stage LC than late stage (23.6 % and 22.3 %, respectively).ConclusionTOP2A, ACTR3, RPS6KA5 and PSIP1 can elicit humoral immune response in LC and their autoantibodies have relationship with the tumorigenesis of LC. Anti-TOP2A and anti-ACTR3 have the potential to serve as a serological biomarkers in early stage LC.     

自身免疫疾病相关检测试剂注册技术要点分析

XIE Yi(Center for Medical Device Evaluation,NMPA,Beijing 100081,China)     

百令胶囊治疗自身免疫性甲状腺疾病对患者甲状腺功能及自身抗体水平的影响

目的探究百令胶囊治疗自身免疫性甲状腺疾病对患者甲状腺功能及自身抗体水平的影响。方法选取2019年6月至2020年1月本院收治的98例自身免疫性甲状腺疾病患者,采用随机数字表法分为对照组和观察组,各49例。对照组行甲巯咪唑片治疗,观察组采用百令胶囊治疗,比较两组治疗前后甲状腺功能、自身抗体水平变化情况等。结果治疗后,两组游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)指标均低于治疗前,血清促甲状腺素(TSH)水平明显高于治疗前(P<0.05);治疗后,观察组FT4水平上升程度明显高于对照组,差异有统计学意义(P<0.05)。两组促甲状腺受体抗体(TRAb)、甲状腺过氧化物酶抗体(TPOAb)、抗甲状腺球蛋白抗体(TGAb)均明显低于治疗前,差异有统计学意义(P<0.05);观察组TRAb(1.67±0.36)U/L,TPOAb(25.91±6.94)U/ml,TGAb(22.91±6.83)IU/ml,明显低于对照组的(2.39±0.59)U/L、(34.54±7.38)U/ml、(39.27±5.80)IU/ml(P<0.05)。结论采用百令胶囊治疗自身免疫性甲状腺疾病能有效提高患者的自身抗体水平,改善患者甲状腺功能,且无其他明显不良反应,值得临床推广应用。     

抗ENO1抗体与狼疮性视网膜病变的相关性

目的: 研究抗α烯醇化酶抗体[抗ENO1(enolase 1)抗体]水平与狼疮性视网膜病变及系统性红斑狼疮(systemic lupus erythematosus,SLE)活动性的相关性。方法: 选择2017年4月至2022年5月北京大学人民医院风湿免疫科住院的活动性SLE患者,分为SLE合并和不合并狼疮性视网膜病变两组,同时以年龄匹配且不合并视网膜病变的健康志愿者作为阴性对照组,应用酶联免疫吸附试验(enzyme-linked immunosorbent assay, ELISA)检测各组血清中抗ENO1抗体水平和阳性率,同时收集前两组SLE患者活动性相关的临床特征和实验室结果,分析抗ENO1抗体水平与其他SLE临床资料与实验室指标之间的相关性。结果: SLE合并狼疮性视网膜病变患者眼底出现了多种视网膜病变,占比排名前三的是视网膜出血(14/32,43.75%)、棉絮斑(8/32,25.00%)和视网膜静脉阻塞(3/32,9.38%)。在32例SLE合并狼疮性视网膜病变患者中,有13例(40.63%)出现了两种及以上的视网膜病变。SLE合并狼疮性视网膜病变患者的血清抗ENO1抗体水平和阳性率显著高于不合并狼疮性视网膜病变组(P < 0.05),狼疮性视网膜病变患者具有更高的SLE疾病活动度评分(P < 0.001)。将SLE患者分为抗ENO1抗体阳性和阴性两组进行研究发现,在临床表现上,抗ENO1抗体阳性与发热和尿潜血有关的可能性大(P=0.011,P=0.042);在实验室指标上,与抗ENO1抗体阴性的SLE患者相比,抗ENO1抗体阳性的SLE患者具有更高的红细胞沉降率(erythrocyte sedimentation rate, ESR)、免疫球蛋白G(immunoglobulin G, IgG)和血小板计数(blood platelet count, PLT,P < 0.01),此外,抗ENO1抗体阳性患者还具有更高的免疫球蛋白A(immunoglobulin A, IgA,P < 0.05)。结论: 合并狼疮性视网膜病变的SLE患者血清中抗ENO1抗体的水平和阳性率明显升高,且具有更高的疾病活动性。     

Bicaudal D2 is a novel autoantibody target in systemic sclerosis that shares a key epitope with CENP-A but has a distinct clinical phenotype

We studied the clinical correlations and epitopes of autoantibodies directed to a novel autoantigen, Bicaudal D (BICD2), in systemic sclerosis (SSc) and reviewed its relationship to centromere protein A (CENP-A). 451 SSc sera were tested for anti-BICD2 using a paramagnetic bead immunoassay and then univariate and multivariate logistic regression was used to study the association between anti-BICD2 and demographic and clinical parameters as well as other SSc-related autoantibodies. Epitope mapping was performed on solid phase matrices. 25.7% (116/451) SSc sera were anti-BICD2 positive, of which 19.0% had single specificity anti-BICD2 and 81.0% had other autoantibodies, notably anti-CENP (83/94; 88.3%). Compared to anti-BICD2 negative subjects (335/451), single specificity anti-BICD2 subjects were more likely to have an inflammatory myopathy (IM; 31.8% vs. 9.6%, p = .004) and interstitial lung disease (ILD; 52.4% vs. 29.0%, p = .024). Epitope mapping revealed a serine- and proline-rich nonapeptide SPSPGSSLP comprising amino acids 606–614 of BICD2, shared with CENP-A but not CENP-B. We observed that autoantibodies to BICD2 represent a new biomarker as they were detected in patients without other SSc-specific autoantibodies and were the second most common autoantibody identified in this SSc cohort. Our data indicate that the major cross-reactive epitope is associated with anti-CENP-A but, unlike anti-CENP, single specificity anti-BICD2 antibodies associate with ILD and IM.     

Cobalt hip prosthesis intoxication mimicking an autoimmune disease

Cobalt-containing hip prosthesis may cause systemic toxicity due to the release of cobalt from metal-on-metal (MoM) joint arthroplasty into the bloodstream. High cobalt blood levels can lead to a variety of clinical manifestations, mimicking other disorders, especially autoimmune, hematologic, and infectious diseases. Our purpose is to describe a clinical case of cobalt hip prosthesis intoxication mimicking an autoimmune disease, with systemic inflammation signs, arthro-myalgias unrelated to overt synovitis, and multiple autoantibody positivity. A 69-years-old woman presented with a 1-year history of right coxalgia, recurrent fever, arthro-myalgias, mediastinal and right iliac reactive lymphadenopathy. She underwent hip replacement surgery seven years earlier. The physical examination was unremarkable except for right hip pain. Laboratory tests showed markedly increased inflammatory indices and microbiological tests were all negative. Ultrasound-guided arthrocentesis of right hip yielded limpid fluid with negative cultures. Increased cobalt levels in plasma and urine showed metal intoxication. Magnetic resonance imaging with metal artifact reduction sequence (MARS) confirmed a periprosthetic mass as usually seen in reaction to metal debris. Prosthesis substitution was performed with a resolution of the clinical picture and normalization of cobalt levels.     

甲状腺过氧化物酶抗体对酶活性的影响

观察ＴＰＯＡｂ阳性的ＡＩＴＤ血清与免疫亲和层析纯化的ＴＰＯ制剂反应后的酶活性变化。结果表明ＴＰＯＡｂ阳性血清（ｎ＝３２）与ＴＰＯ反应后酶活性较正常对照（ｎ＝３４）低（Ｐ＜０．０５），但ＴＰＯＡｂ或ＴＭＡｂ结合率与酶活性抑制程度无显著性相关。Ｇｒａｖｅｓ病（ｎ＝１３）、桥本甲状腺炎（ｎ＝１２）、原发性甲减（ｎ＝７）血清对酶活性的抑制程度差异无显著性。提示ＴＰＯＡｂ对酶活性的直接抑制作用与抗体的生物学特性有关，而与甲状腺功能或病理状态无关。     

M2抗体人源靶抗原三联体的克隆表达及其在原发性胆汁性肝硬化中的应用

目的 设计克隆表达抗原蛋白三联体BPO，利用纯化的重组BPO，建立原发性胆汁性肝硬化(primary biliary cirrhosis，PBC)特异性免疫学诊断方法。方法 利用基因工程方法克隆表达M2抗原及其三联体BP0，并加以鉴定。纯化BPO，建立ELISA法。应用ELISA法检测17例PBC患血清M2抗体，以167例非PBC患和1225例健康人作对照。结果 17例临床诊断为PBC的患，M2抗体均为阳性，而对照组M2抗体均为阴性。结论 本法检测M2抗体有较好的敏感性及特异性，为PBC的临床诊断提供了有效手段。