Cartilage oligomeric matrix protein in serum in systemic lupus erythematosus and knee osteoarthritis. Preliminary communication

The cartilage oligomeric matrix protein (COMP) is a glycoprotein, which occurs mainly in an articular cartilage. The amount of this protein increases under the influence of cytokines and growth factors. As a result of various diseases that cause damage to cartilage, fragments of matrix protein are released into synovial fluid and then into blood. The assessment of matrix protein level in serum, for example COMP, permits the establishment of the degree of cartilage damage in inflammatory joint diseases, and permits observation of the effectiveness of the treatment. Blood was collected from 30 systemic lupus erythematosus (SLE) patients, and from 30 patients with knee osteoarthritis (OA) who constituted the control group. Serum COMP level was determined using an inhibition enzyme-linked immunosorbent assay (ELISA). The average value of the serum COMP level in SLE patients was 11.3±3.7 U/l. According to correlation coefficients, serum COMP level is independent of patients age, disease duration and the clinical picture of SLE. No correlation was found between serum COMP level and bone mass density (BMD) changes. In SLE patients with decreased haemoglobin levels (<11.0 g/dl) values compared with patients with normal haemoglobin level, the serum COMP level was observed to be significantly higher (P<0.05). Both in SLE patients with erythrocyte sedimentation rate (ESR) values over 60 mm/h and in patients with ESR values below 60 mm/h, the serum COMP level was observed to be significantly higher (P<0.05). A significant positive correlation was found between serum COMP level and ESR value, as well as a number of thrombocytes. Negative correlation occurred between the serum COMP level and the value of haemoglobin. The average value of COMP in OA patients was 10.4±2.7 U/l. No correlation was found between serum COMP level and patients age and disease duration. There was correlation between the serum COMP level and the T-score value of densitometry examinations in OA patients. No statistical differences were found between the average serum COMP levels for SLE and OA patients.     

Systemic lupus erythematosus associated with recurrent lupus enteritis and peritonitis

We describe the case of a 41-year-old woman with systemic lupus erythematosus (SLE) who suffered from repeated reversible lupus enteritis characterized by marked edematous thickening of the small intestine. Ultrasonography (US) and computed tomography (CT) manifested as an accordion-like appearance and a target-like appearance, respectively. Resolution of gastrointestinal tract wall thickening was observed on follow-up US performed a week after the increase in predinosolone (PSL). We conclude that careful evaluation of sonographic and radiographic findings helps to establish the diagnosis of lupus enteritis.Abbreviations CT Computed tomography - FANA Fluorescent antinuclear antibody - GI Gastrointestinal - SLE Systemic lupus erythematosus - US Ultrasound     

Systemic lupus erythematosus after coronavirus disease-2019 (COVID-19) infection: Case-based review

BackgroundCoronavirus disease-2019 (COVID-19) is a novel infectious disease, which presents with various clinical manifestations. There is growing evidence of an association between COVID-19 infection and autoimmune diseases. The aim of this case report was to demonstrate the association of COVID-19 infection and the development of systemic lupus erythematosus (SLE).Case presentationA 38 year old Iranian woman presented with progressive icterus, pleuritic chest pain, palpitation, dyspnea, photosensitivity and arthralgia 18-days after COVID-19 symptoms proved by a positive polymerized chain reaction (PCR). The chest and abdomen computerized tomography (CT) scan showed pericardial and pleural effusion and enlarged liver and abdominal lymph nodes. Antinuclear antibody (ANA), anti-double stranded deoxyribonucleic acid (anti-ds DNA) antibody and perinuclear anti-neutrophil cytoplasmic antibody (P-ANCA) were positive. She was diagnosed as SLE and was successfully treated with prednisolone 30 mg daily, hydroxychloroquine 200 mg daily and azathioprine 150 mg daily and she remarkably improved. Repeated anti-ds DNA antibody was positive. Due to nausea and abdominal discomfort, azathioprine was discontinued and replaced with mycophenolate mofetil 1500 mg daily. In the article, similar cases were presented; the mean interval between COVID symptoms and SLE presentations was 24.86 days. Pulmonary and renal involvements were the most common presentations of SLE triggered by COVID-19. The most frequently reported autoantibody was ANAConclusionIt is necessary to be aware of the development of lupus disease in COVID-19 infected patients, because prompt diagnosis and treatment is very important to improve their outcome.     

难治性狼疮性肾炎多靶点治疗前瞻性临床研究

目的以静脉环磷酰胺(CTX)冲击后续硫唑嘌呤(Aza)维持治疗为对照,前瞻性研究普乐可复(FK506)、霉酚酸酯(MMF)联合激素治疗狼疮性肾炎(LN)的疗效和安全性. 方法经肾活检诊断为Ⅳ、Ⅳ+Ⅴ、Ⅲ+Ⅴ型和Ⅴ型活动性LN 92例,男女比例为1676,年龄在12～60岁,随机分为多靶点治疗组(诱导期FK506剂量为3～4 mg/d,MMF剂量为0.75～1.0 g/d;维持期剂量FK506剂量为1.5～2.0 mg/d,MMF剂量为0.5～0.75 g/d)和CTX-Aza组[诱导期采用IVC治疗0.5～1.0 g/m2BSA,1/月,维持期予Aza治疗1～2 mg/(kg·d)].总疗程18个月,诱导期初定6个月;若6个月内未达完全缓解(CR),诱导期延长至9个月.两组患者均采用静脉甲基泼尼松龙冲击治疗后口服泼尼松[起始剂量0.6 mg/(kg·d)]治疗.主要评价指标为诱导治疗期完全缓解率(CR,定义为尿蛋白定量＜0.4 g/24h,尿红细胞＜10万/ml,无管型尿和白细胞尿,血白蛋白≥35 g/L,SCr正常或上升不超过基础值的15%. 结果(1)多靶点治疗组Ⅳ型LN诱导治疗期CR率与CTX-Aza组差异无统计学意义(75.0% vs 60.0%,P＞0.05).(2)多靶点治疗组Ⅳ+Ⅴ型LN诱导治疗期CR率显著高于CTX-Aza组(75.0% vs 16.7%.P＜0.05).并且治疗9个月时多靶点治疗组尿蛋白正常的患者比例也显著高于CTX-Aza组(72.7% vs 16.7%,P＜0.05).(3)多靶点治疗组,Ⅳ型、Ⅳ+Ⅴ型LN患者诱导治疗期CR率都较高,均为75.0%,其次是Ⅲ+Ⅴ型(66.7%).Ⅴ型LN诱导治疗期CR率最低,仅16.7%,显著低于Ⅳ型、Ⅳ+Ⅴ型LN(P＜0.05).(4)诱导治疗期由6个月延长至9个月后,多靶点治疗组Ⅳ+Ⅴ型LN、CTX-Aza组Ⅳ型和Ⅳ+Ⅴ型LN的CR率有所增加.(5)多靶点治疗组24例患者在诱导治疗完成后接受重复肾活检,结果显示肾组织AI评分均值由9.0±4.0降至2.1±1.7(P＜0.01),AI≥8分的患者比例也由75%降至4.2%(P＜0.01).同时肾组织CI评分均值由0.7±1.0增至2.2±1.3(P＜0.01),CI≥3分的患者比例从12.5%增加至37.5%(P＜0.05).(6)多靶点治疗组的不良反应包括肝酶升高、胃肠道症状、白细胞减少、感染、脱发、血压升高、糖代谢异常等,未见月经紊乱和停经报告.多靶点治疗组胃肠道症状、WBC减少、上呼吸道感染的发生率显著低于CTX-Aza组(P＜0.05);血压升高发生率则高于CTX-Aza组(17.74% vs 0%,P＜0.05). 结论多靶点诱导治疗对Ⅳ型、Ⅳ+Ⅴ型和Ⅲ+Ⅴ型LN均有显著疗效,并且不良反应较少,安全性较高.     

抗嗜中性粒细胞胞浆抗体与狼疮性肾炎的关系

目的探讨抗嗜中性粒细胞胞浆抗体（ANCA）与狼疮性肾炎（LN）临床相关表现和发病机制的关系。方法分别应用间接免疫荧光法和酶联免疫吸附分析的方法,检测81例LN患者血清中的ANCA,并分析ANCA与LN临床表现和其它实验室检查结果之间的关系。结果单用间接免疫荧光法检测时,ANCA在LN中的阳性率是30.9％（25／81）。对间接免疫荧光法检测为阳性的血清,用酶联免疫吸附分析法进行验证,结果仅有72.0％（18／25）仍为阳性,全部是核周型ANCA（p-ANCA）,未见中央型ANCA（c-ANCA）出现。ANCA阳性组LN患者合并浆膜炎、神经系统累及、贫血、抗ds-DNA抗体阳性和低补体的频率均显著高于ANCA阴性组LN患者。结论ANCA在LN中的阳性率为30.9％,并与LN特定的临床表现相关,提示ANCA可能参与了LN的发病过程。     

霉酚酸酯治疗35例Ⅳ型狼疮性肾炎的长期随访

目的回顾性总结霉酚酸酯(MMF)治疗Ⅳ型狼疮性肾炎(LN)的临床疗效,探讨MMF的剂量,了解复发情况.方法35例活动性LN患者(其中10例为初治,25例已经使用大剂量激素或联合间断环磷酰胺静脉冲击疗法),采用MMF联合激素治疗6个月以上.所有患者治疗前尿蛋白＞2.0g/24h,有明显血尿或管型尿,肾活检显示活动性Ⅳ型LN.MMF起始剂量1.0～1.5g/d,初治患者同时给予足量激素诱导治疗,对已经使用大剂量激素者继续口服中、小剂量强的松.疗效标准分为缓解、部分缓解及无效.在患者病情明显好转后MMF逐步减至0.5～0.75g/d维持.结果①MMF治疗时间6～36个月(平均12.7±6.8月).在治疗期间共有27例(占77.1%)获得缓解(尿蛋白＜1.0g/d,无活动性尿沉渣、肾功能稳定、血清A-dsDNA阴性,无肾外活动),6例获部分缓解,2例无效.获得缓解的时间为3～15个月(平均6.5±4.7月).随着MMF治疗时间延长,缓解率逐步增高MMF治疗3、6、12、24个月的缓解率分别为25.7%、60%、72.7%及83.3%.18例患者减量或停药前行重复肾活检,肾组织活动性指数显著下降.②30例患者在治疗3～6个月,临床获得缓解或部分缓解后开始减量.在MMF维持治疗3～9个月间12.5%患者复发,7例患者停用MMF3～9个月后3例复发.③治疗过程中各有2例患者并发肺炎及疱疹病毒感染,未见肝功能异常及白细胞减少.结论MMF1.0～1.5g/d剂量联合激素治疗能有效控制狼疮性肾炎活动,诱导治疗时间应6个月以上.在获得缓解或部分缓解后MMF可逐步减量,但维持剂量不宜太小.停止MMF治疗后复发率高,因此必须有替代药物治疗以降低MMF停药后的高复发率.     

Prospective study of low-dose cyclosporine A in patients with refractory lupus nephritis

We evaluated the efficacy and safety of low-dose cyclosporine A (CsA) in patients with refractory lupus nephritis. Nine patients with systemic lupus erythematosus who had lupus nephritis resistant to previous treatment with glucocorticoids and immunosuppressants other than CsA were enrolled in a prospective, open-label study. All patients initially received 2.5 mg/kg per day of CsA; the dosage was adjusted to reach a blood trough level of 80–150 ng/ml. The urinary protein concentration decreased significantly 2 weeks after the initiation of treatment. After 30 weeks of CsA treatment, the mean urinary protein concentration was more than 50% lower than the baseline value, and urinary casts had decreased significantly. There were no significant changes in the levels of serum creatinine, serum anti-double-stranded DNA antibodies, or CH50 during any part of the study. The dose of glucocorticoids was significantly tapered by approximately 50%, without any disease flare. Hypertension developed in one patient, but was controlled with antihypertensive agents. Our results suggest that low-dose CsA therapy is an effective and less toxic alternative to conventional cyclophosphamide therapy for the management of refractory lupus nephritis.     

Estrogen receptor expression by peripheral blood mononuclear cells of patients with systemic lupus erythematosus

To investigate the influence of sex hormones on the development of systemic lupus erythematosus (SLE), we examined the estrogen receptor (ER) expression by peripheral blood mononuclear cells (PBMC) in patients with SLE using the real-time quantitative polymerase chain reaction (TaqMan) method. The expression of messenger RNA (mRNA) for ER alpha (ERa) was increased and expression of ER beta (ERb) mRNA was decreased in PBMC from SLE patients compared with PBMC from normal controls. These findings may be useful for elucidation of the pathophysiology of SLE.     

A multicenter phase I/II trial of rituximab for refractory systemic lupus erythematosus

Although corticosteroids and immunosuppressants are widely used for the treatments of systemic lupus erythematosus (SLE), safer and more effective therapies are prerequisite. We and others have reported that anti-CD20 antibody rituximab targeting B cells are effective for refractory SLE and, therefore, safety and clinical efficacy of rituximab in SLE was evaluated by a multicenter phase I/II clinical trial. An open-label, multicenter study of 15 patients with active and refractory SLE (total British Isles Lupus Assessment Group [BILAG] score 8 to 17) was conducted. Rituximab was administered to 5 SLE patients as 4 infusions of 500 mg/body every week and to 10 SLE patients as 2 infusions of 1000 mg/body every other week. Assessment of safety, infusion reactions and adverse effects was used as the primary outcome for clinical tolerability and was evaluated by 28 weeks. Rituximab was well tolerated, with most experiencing no significant adverse effects. B cells rapidly reduced in all patients and remained low until 6 months post-treatment. Four patients developed human antichimeric antibodies without affecting efficacy of rituximab. Changes in routine safety laboratory tests clearly related to rituximab were not observed. Nine among 14 evaluable patients achieved the major or partial clinical response of BILAG score and prednisolone dose significantly decreased at the 28 weeks. Rituximab therapy appears to be safe for the treatment of active SLE patients and holds significant therapeutic promise, at least for the majority of patients experiencing profound B-cell depletion.