儿童系统性红斑狼疮与肾炎慢病管理及治疗进展

儿童系统性红斑狼疮（childhood-onset systemic lupus erythematosus，cSLE）是特指在18岁之前发病的系统性红斑狼疮。可累积全身多脏器、多系统，有多达60%的患儿会出现狼疮性肾炎（lupus nephritis，LN），其中19%的患儿进展为终末期肾病。感染和终末期肾病是导致发展中国家cSLE死亡的常见原因。由于疾病本身和治疗都会影响患儿的身心和生长发育，做好cSLE与LN的慢病管理对控制病情、提高长期生存率极为重要。本文总结了近年来国内外系统性红斑狼疮慢病管理的经验，并对cSLE与LN慢病管理和治疗进展进行综述，旨在提高治疗达标率，减少疾病复发及并发症的发生，使患儿获益。     

Instability of the extensor digitorum tendons in Jaccoud arthropathy assessed by semi-dynamic MRI of the metacarpophalangeal joints

PurposeThe purpose of this study was to test the hypothesis that Jaccoud arthropathy (JA) in patients with systemic lupus erythematosus (SLE) is associated with instability of the extensor digitorum (ED) tendons during flexion of the metacarpophalangeal (MCP) joints by comparing the position of the ED tendons between SLE patients with JA and control subjects on hand MRI obtained with flexed and extended MCP joints.Materials and methodsThirty-two hands of SLE patients with JA (13 women and 3 men; mean age, 50.0 ± 12.2 [SD] years; age range: 26–68 years) and 24 hands of sex- and age-matched control subjects (20 women and 4 men; mean age, 50.1 ± 13.0 [SD] years; age range: 24–68 years) were included in the study. Axial spin echo T1-weighted MRI images of the second to fifth MCP joints in flexion and in extension were obtained. Two radiologists (R1 and R2) separately measured the amplitude and assessed the direction of the displacement of the ED tendons with respect to the midline at the level of each MCP joint. Statistical analysis included two-way ANOVA with random effects to assess differences in amplitude and Fisher–Freeman–Halton exact test to assess differences in direction with P-values < 0.0083 and < 0.0063 considered as statistically significant respectively.ResultsAmplitude of the displacement of the ED tendons was statistically significantly greater in SLE patients with JA than in control subjects in flexion for both readers (median 58°, 95% confidence interval [CI]: 50°–65° vs. 20°, 95% CI: 16°–24°; P < 0.0001 for R1 and 54°, 95% CI: 47°–61° vs. 25°, 95% CI: 22°–28°; P < 0.0001 for R2) and in extension for one reader (17°, 95% CI: 15°–20° vs. 14°, 95% CI: 11°–16°; P = 0.0048 for R1 and 20°, 95% CI: 15°–25° vs. 16°, 95% CI: 12°–18°; P = 0.0292 for R2). Ulnar deviation of the ED tendons was statistically significantly more frequent in SLE patients with JA than in control subjects in flexion and in extension for both readers (P < 0.0001).ConclusionJA is associated with instability of the ED tendons in patients with SLE best depicted when MCP joints are flexed.     

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.     

狼疮肾炎合并抗磷脂抗体综合征的中西医结合诊疗

抗磷脂抗体综合征(APS)是系统性红斑狼疮(SLE)常见继发病症。以循环中出现抗磷脂抗体、血栓形成和病态妊娠为特征性表现。合并APS的狼疮肾炎(LN)患者易出现更多并发症，预后较差，对治疗的敏感性降低。抗凝和(或)抗血小板是治疗LN合并APS的关键，血浆置换则对重症APS患者有一定疗效。近年来，新型药物与治疗方法如利伐沙班、美罗华及干细胞移植展现出了巨大的治疗潜力。中西医结合治疗是另一种极有希望的治疗方法，多位中医大家均认为活血化瘀法可有效治疗LN合并APS患者。现代临床与药理研究也发现了中药治疗LN合并APS的价值。     

过敏性紫癜性肾炎方药规律及中医证候分析

目的：通过对1993年1月至2019年12月CNKI、VIP、WanFang收录的中医治疗过敏性紫癜性肾炎的文献进行整理分析，探讨中医辨证论治本病的证候和方药规律。方法：采用SPSS 25.0统计软件，对文献中证候、方剂以及药物进行统计归类，总结各证候、方剂、药物出现的频次和所占比例，对药物和临床症状进行聚类分析。结果：共纳入文献93篇，通过整理分析得出39个中医证候，其中脾肾两虚、风盛血热、气不摄血、阴虚火旺、气阴两虚等为中医常见证候；证候要素分析：血热、风热、瘀血、湿热为常见实性病机；肾虚、脾虚、阴虚、气虚为常见虚性病机；病位主要在肾、脾、肺、肝四脏；共得方剂145首，其中自拟方53首，成方92首，二者以补益剂、清热剂、理血剂、祛风剂为主；中药206味，分为13类，以生地黄、牡丹皮、赤芍、当归、茯苓等为常用药。结论：过敏性紫癜性肾炎的病位在肾、脾、肺、肝；风、热、湿、毒、瘀、虚为本病的主要病机。在临床用药中以补虚药、活血药、清热解毒药、利水渗湿药为主，兼以应用祛风药；治疗中应采用中医辨证与辨病相结合的方式。     

雷公藤多苷辅助治疗狼疮性肾炎的Meta分析

目的:系统评价雷公藤多苷联合西药治疗狼疮性肾炎（LN）的疗效。方法:计算机检索2009—2019年中国知网、维普数据库、万方数据库、PubMed数据库及Springer电子期刊,查找以雷公藤多苷联合西药治疗LN的随机对照试验(RCT),按纳入标准和排除标准筛选文献、提取资料和评价纳入研究的方法学质量后,采用Revman5.3软件进行Meta分析。结果:1)共纳入8篇文章,657例患者,其中观察组330例,对照组327例,各研究均明确指出基线均衡,具有可比性。2)Meta分析结果显示:雷公藤多苷辅助治疗LN在提高缓解率(OR=1.58,95%CI［1.08,2.32］,P=0.02),降低血尿素氮(MD=-1.14,95%CI［-2.13,-0.14］,P=0.03),降低血肌酐(MD=-9.93,95%CI［-17.94,-1.93］,P=0.02),提升血清白蛋白(MD=3.99,95%CI［0.82,7.17］,P=0.01),增加补体C3(MD=0.16,95%CI［0.05,0.27］,P=0.003),增加补体C4(MD=0.09,95%CI［-0.03,0.15］,P=0.003)等方面明显优于单用激素或免疫抑制剂等西药治疗,其差异有统计学意义。在降低24 h尿蛋白及发生不良反应等方面无统计学意义。结论:本次Meta分析显示雷公藤多苷辅助治疗LN对比单纯使用西药(激素、免疫抑制剂、细胞毒性药物),在提高缓解率,升高血清白蛋白,降低血尿素氮、血肌酐及提高补体C3、C4方面疗效突出,差异均有统计学意义。但由于此次收录的文献质量相对不高,样本数量较少,未来更需要更多高质量,大样本,研究设计方案更严谨的随机对照试验,对雷公藤多苷辅助治疗LN有更精确的评估。     

狼疮肾炎患者自噬水平及其对足细胞相关蛋白表达水平的影响

目的探讨狼疮肾炎(lupus nephritis,LN)患者自噬水平及其对足细胞相关蛋白表达水平的影响。方法选择2017年5月至2019年5月于榆林市第一医院收治的69例LN患者为LN组,50例系统性红斑狼疮(systemic lupus erythematosus,SLE)患者为SLE组,50例肾切除手术患者为对照组,观察3组肾脏足细胞内自噬体数量,比较3组肾脏组织中自噬相关蛋白、微管相关蛋白轻链3(LC3)、B淋巴细胞瘤蛋白质-2-相互作用蛋白(Beclin1)的表达,以及足细胞相关蛋白,肾病蛋白(Nephrin)、足突蛋白(Podocin)的表达。分离狼疮肾炎患者肾脏足细胞,将足细胞分为自噬抑制组和自噬诱导组,自噬抑制组加入100 nmol/L 3-甲基腺嘌呤(3-MA),自噬诱导组加入100 nmol/L雷帕霉素(RAPA),比较3组足细胞内自噬体数量及LC3、Beclin-1、Podocin、Nephrin等蛋白的表达。结果LN组、SLE组肾脏足细胞内自噬体数量及LC3、Beclin-1、Podocin、Nephrin蛋白表达量显著高于对照组(P<0.05);SLE组肾脏足细胞内自噬体数量及LC3、Beclin-1、Podocin、Nephrin蛋白表达量显著高于LN组(P<0.05);自噬诱导组足细胞内自噬体数量及LC3、Beclin-1、Podocin、Nephrin蛋白表达量显著高于正常对照组、自噬抑制组(P<0.05);正常对照组足细胞内自噬体数量及LC3、Beclin-1、Podocin、Nephrin蛋白表达量显著高于自噬抑制组(P<0.05)。结论LN患者自噬水平呈升高状态,自噬水平升高可能通过上调足细胞相关蛋白Podocin、Nephrin水平而减轻足细胞损伤,抑制LN病情进展。     

2018年系统性红斑狼疮研究新进展

【摘要】 系统性红斑狼疮是一种主要累及中青年女性的复杂自身免疫疾病，临床表现多样，发病机制复杂。对于系统性红斑狼疮的研究一直是国内外自身免疫疾病领域的热点，本文主要综述2018年系统性红斑狼疮的基因组学与临床研究取得的新成果和进展。