Anti-alpha-actinin antibodies are part of the anti-cell membrane antibody spectrum that characterize patients with lupus nephritis

Anti-membrane autoantibodies (MbA) have been reported in sera from patients with lupus nephritis (LN) but the targets of the MbA remain to be explored, which is the aim of the current study. Sera were collected from 40 patients with LN determined by renal biopsy, and from 30 systemic lupus erythematosus (SLE) patients without clinical evidence of LN. Thirty autoimmune disease control patients (rheumatoid arthritis, Sjögren's syndrome and systemic sclerosis), and 30 healthy controls were also included. Using flow cytometry, the presence of anti-MbA was explored revealing that IgG anti-MbA positivity was associated with LN (62.5% vs 13.3%) when compared to non-LN SLE patients, autoimmune disease patients (6.7%) and healthy controls (0%). Next, using purified plasma membrane fractions from human embryonic kidney (HEK) cells, the more prominent targets and their occurrence rates were located at 50 kDa, 60/65 kDa, 90 kDa, 110 kDa, 180 kDa and 220 kDa. Alpha-actinin (110 kDa) autoAb was characterized as a major target in LN patients positive for anti-MbA, and anti-MbA binding activity was reduced (36.9 ± 13.7%) in the presence of α-actinin. Laminin (200 kDa) was also characterized as a minor target, which was not the case for annexin A2 (36 kDa). Finally, anti-MbA IgG subclass analysis indicated a predominance of IgG2. In conclusion, IgG anti-MbA were detected at high levels in LN patients supporting a primary pathogenic role for anti-MbA and anti-MbA/α-actinin+ in LN that needs further research.     

Deleting the BAFF receptor TACI protects against systemic lupus erythematosus without extensive reduction of B cell numbers

B cell-activating factor of the TNF family (BAFF) is an essential B cell survival factor. However, high levels of BAFF promote systemic lupus erythematosus (SLE) in mice and humans. Belimumab (anti-human BAFF) limits B cell survival and is approved for use in patients with SLE. Surprisingly, the efficacy of rituximab (anti-human CD20) in SLE remains controversial, despite depleting B cells more potently than belimumab. This raises the question of whether B cell depletion is really the mechanism of action of belimumab. In BAFF transgenic mice, SLE development is T cell-independent but relies on innate activation of B cells via TLRs, and TLR expression is modulated by the BAFF receptor TACI. Here, we show that loss of TACI on B cells protected against BAFF-mediated autoimmune manifestations while preserving B cells, suggesting that loss of BAFF signaling through TACI rather than loss of B cells may underpin the effect of belimumab in the clinic. Therefore, B cell-sparing blockade of TACI may offer a more specific and safer therapeutic alternative to broad B cell depletion in SLE.     

Lupus arthropathy: historical evolution from deforming arthritis to rhupus

Systemic lupus erythematosus is an autoimmune and inflammatory disease with multiple clinical manifestations, including arthropathy. The clinical presentation of articular involvement is variable, ranging from arthralgia without erosions or deformity to an erosive arthropathy and severe functional disability. A subset of patients with this articular involvement have Jaccouds arthropathy, and others have an arthropathy with clinical findings similar to rheumatoid arthritis that has been called rhupus. In this paper we review the historical evolution of concepts of lupus arthropathy, from deforming arthritis to rhupus, and conclude that rhupus is not a combination of rheumatoid arthritis and lupus. Instead, rhupus arthropathy should be regarded as a variant of the arthropathy of systemic lupus erythematosus.     

重症监护病房系统性红斑狼疮患者预后因素分析

Objective To analyze the outcomes and prognostic factors associated with the death of systemic lupus erythematosus (SLE) patients admitted to the intensive care unit (ICU). Methods During June 1996 to June 2007, all SLE patients admitted to the ICU were included. Patients were excluded if the diagnosis of SLE was established at or after ICU admission. A multivariate logistic regression model was applied using variables that were associated with death in the univariate analysis. Results A total of 101 patients meeting the criteria were included. The mortality rate was 48.6%. The most common causes of admission was lung disorder with acute respiratory distress syndrome (ARDS). Multivariate logistic regression analysis suggested that SLICC/ACR DI>7.7 (OR=6.87), APACHE Ⅲ≥21 (OR=29.8), lung disorders with ARDS (OR =55.81 ), septic shock (OR =32.22 ), intracranial haemorrhage (OR =57.35 ), hypocytopenia (OR = 5.89), mean equivalent prednisone dose>25 mg/d (OR=7.65) and prolonged tracheal intubation (OR=5.98) were signi-ficantly associated with death. Whereas sex, age, SLEDAI >27, gastrointestinal bleeding, the cumulative dosage of CTX higher than 1.0 g, pulse intravenous methylprednisolone therapy were not associated with death. Conclusion The mortality rate of critically ill SLE patients in ICU is very high. SLICC/ACR DI> 7.7, APACHE Ⅲ≥21, lung disorders with ARDS, septic shock, intracraniai haemorrhage, average prednisone equivalent dosage higher than 25mg/d and prolonged tracheal intubation (longer than 4 days) are negative prognostic factors in SLE patients admitted to the ICU.     

系统性红斑狼疮合并结核感染临床特征及外周血淋巴细胞亚群分析

目的: 探讨系统性红斑狼疮(systemic lupus erythematosus,SLE)合并结核感染患者的临床特征及其外周血淋巴细胞亚群的特点。方法: 采用回顾性研究方法,搜集2015年1月至2021年12月深圳市人民医院收治并同时完成γ-干扰素释放试验及淋巴细胞亚群检测的287例SLE患者作为研究对象。其中,SLE合并活动性结核病者30例(结核病组),SLE合并结核分枝杆菌潜伏感染(latent tuberculosis infection,LTBI)者16例(LTBI组)。按SLE合并活动性结核病组1∶2的比例,选取同时期性别、年龄匹配的未合并结核分枝杆菌及其他病原体感染的SLE患者60例,作为未感染组。同时,从本院体检中心纳入性别、年龄与SLE合并活动性结核病组相匹配,并完成淋巴细胞亚群检测的健康成年人40名,作为对照组。收集研究对象临床特征、实验室检测结果及临床治疗资料等进行分析。结果: 结核病组的结核病病程为4.0(1.0,8.0)周,以合并单纯肺结核为主[17例(56.7%)]。结核病组的SLE病程为54.0(7.5,96.0)月,明显短于LTBI组[96.0(72.0,180.0)月],而出现间质性肺炎的比例[23.3%,7例]明显多于LTBI组(0.0%),差异均有统计学意义(Z=-2.832,P=0.005;χ²=4.403,P=0.036)。与未感染组相比,结核病组的CD3⁺ T细胞计数[(766±480)个/μl vs. (1146±636)个/μl]、CD4⁺ T细胞计数[(370±278)个/μl vs.(517±291)个/μl]和CD8⁺ T细胞计数[376(244,421)个/μl vs.420(322,742)个/μl]明显降低,差异均有统计学意义(t=-2.875,P=0.005;t=-2.298,P=0.024;Z=-2.842,P=0.004)。3组SLE患者的淋巴细胞亚群比例均无明显差异。结论: SLE患者合并的结核感染多累及肺部;SLE合并活动性结核病患者发生间质性肺炎的比例较高。临床治疗中,如SLE患者出现T淋巴细胞减少,尤其CD8⁺ T细胞严重减少时,应警惕结核感染。     

泼尼松联合霉酚酸酯对比环磷酰胺治疗狼疮性肾炎的系统评价

目的系统评价泼尼松联合霉酚酸酯与环磷酰胺治疗狼疮性肾炎的疗效及安全性。方法检索Pub Med、MEDLINE、Embase、Cochrance图书馆临床对照试验资料库、中国期刊全文数据库(CNKI)、中文科技期刊全文数据库(维普)和万方数字化期刊全文库等,检索泼尼松联合霉酚酸酯(MMF)与环磷酰胺(CTX)治疗狼疮性肾炎的随机对照临床试验(检索时间均从建库至2013年12月),对完全缓解率、部分缓解率、总缓解率、感染、白细胞减少、胃肠道反应进行Meta分析。结果共纳入22篇文献(共1 641例),Meta分析结果显示,与泼尼松+CTX组比较,泼尼松+MMF组的完全缓解率及总缓解率高(P<0.01),而感染率、白细胞减少发生率低(P<0.01),两组间部分缓解率及胃肠道反应比较差异无统计学意义(P>0.05)。结论泼尼松联合MMF治疗狼疮性肾炎的缓解率较泼尼松联合CTX高,感染及白细胞减少的风险较小。     

Clinical utility of urinary soluble CD163 in evaluation of lupus nephritis patients

Aim of the workTo assess urinary soluble CD163 (sCD136) in systemic lupus erythematosus (SLE) patients compared to healthy controls. In addition to determine its association with different SLE clinical features, laboratory investigations and pathological indices focusing on those suggest renal disease activity.Patients and methodsThe study included 58 SLE patients and 30 controls. SLE disease activity index (SLEDAI) was assessed and patients subdivided into active lupus nephritis (ALN) (renal SLEDAI ≥ 4) and no-renal activity (NRA) SLE patients (renal SLEDAI = 0). Urinary sCD163 was measured by Enzyme-Linked Immunosorbent Assay (ELISA). Urine values were normalized to urinary creatinine excretion. Renal biopsies were performed in 21 ALN patients.ResultsThey were 54 females and 4 males with a mean age 31.8 ± 9.1 years and disease duration 6.2 ± 4.8 years. They were 31 with ALN and 27 NRA SLE patients. Urinary sCD163 level was significantly higher in SLE patients (1.85 ± 0.3) than controls (0.5 ± 0.36, p < 0.001). In ALN, it was significantly higher (2.91 ± 2.52) compared to NRA SLE patients (0.64 ± 0.38) and controls (p < 0.001 in both). The optimum cut-off value above which normalized urinary sCD136 can predict renal activity was > 0.82 with sensitivity of 90.3%, specificity of 88.89%, p < 0.001. Urinary sCD163 significantly correlated with renal (r = 0.75, p < 0.001) but not with extra-renal SLEDAI. It correlated with activity index of renal biopsy (r = 0.46, p = 0.038).ConclusionUrinary sCD163 is a potential biomarker for LN activity. Its level is associated with clinical features, laboratory investigations and pathological indices that indicate renal disease activity.     

血清B淋巴细胞刺激因子在系统性红斑狼疮中的意义

目的 研究血清B淋巴细胞刺激因子（Blys）在系统性红斑狼疮（SEE）中的意义。方法 酶联免疫吸附试验（ELISA）法检测125例SLE患者血清Blys水平，并与狼疮活动程度和临床表现进行相关性分析。结果 125例SLE患者血清平均Blys水平显著高于正常对照组[（0．72±0．18）ng／ml vs（0．34±0．10）ng／ml，P=0．0031]；SLE患者血清平均Blys水平与SLE疾病活动指数（SLEDAI）积分呈一定程度相关性（r=0．73，P=0．018）；SLE患者血清Blys水平与抗dsDNA抗体滴度呈正相关，而与血清IgG、补体、蛋白尿、白细胞、血小板计数，以及皮疹、关节痛、口腔溃疡、脱发、发热等临床表现等均无显著相关性（P〉0．05）。结论 SLE患者血清Blys水平升高，与狼疮活动呈一定相关性，但不能准确反映病变部位及严重程度。     

Drug-related lupus in a patient with rheumatoid arthritis under sulfasalazine treatment

Summary The induction of lupus-like syndromes with the appearance of single-stranded DNA antibodies is a well-known complication of drug therapy. In this report we present a patient with an erosive seropositive rheumatoid arthritis developing the clinical and serological features of systemic lupus erythematosus including the occurrence of double-stranded DNA antibodies under sulfasalazine treatment.