自体外周血纯化造血干细胞移植治疗系统性红斑狼疮

目的 探讨自体外周血纯化造血干细胞移植治疗系统性红斑狼疮(SLE)的疗效和安全性。方法 对9例SLE患者进行自体外周血纯化造血干细胞移植。采集的干细胞的计数为(2.37～9.9)×10⁸/kg。预处理方案是环磷酰胺50 mg·kg^-1·d^-1静脉滴注,连用4 d(造血干细胞回输前2～5d)。抗胸腺球蛋白抗体2.5 mg·kg^-1·d^-1静脉滴注,连用4d。同时碱化和水化尿液,保护心、肝和肾功能。从移植后临床表现、SLE相关的免疫学指标的变化,移植后造血重建情况,移植的并发症等方面进行评价。结果 9例患者均获得成功植入,外周血白细胞总数>1.0×10>/L的时间为移植后7～15 d,血小板>20×10⁹/L时间为移植后0～21d。所有患者均于移植后面部红斑等临床症状完全消失,大部分患者自身抗体转阴。9例患者均出现轻重不一的血清病样反应,1例出现严重的肾衰和心衰,3例有出血性膀胱炎,1例出现心因性精神障碍,1例发生会阴部念珠菌感染。结论 随访1年结果表明,自体外周血纯化造血干细胞移植治疗SLE的近期疗效显著,且相对安全。     

自体外周血造血干细胞移植治疗难治性寻常型天疱疮1例

目的观察自体外周血造血干细胞移植治疗难治性寻常型天疱疮1例的效果。方法患者男,45岁。口腔、头面部、躯干、四肢水疱、糜烂6年。诊断为寻常型天疱疮。经糖皮质激素和免疫抑制剂及抗CD20单克隆抗体治疗,疾病反复发作。同时合并糖尿病和高血压。半年前,全身水疱加重,行自体外周血造血干细胞移植。应用环磷酰胺、粒细胞集落刺激因子（G-CSF）进行动员。用环磷酰胺（CTX）＋磷酸氟达拉滨（Flud）＋抗胸腺细胞球蛋白（ATG）进行预处理。结果患者移植结束后,皮疹消退,自身抗体滴度明显降低。移植2个月后皮疹轻度反复,小量糖皮质激素联合甲氨蝶呤可以控制。目前移植后6个月,病情稳定。结论自体外周血造血干细胞移植治疗难治性寻常天疱疮疗效显著。可作为治疗难治性寻常型天疱疮的一种新方法。但其远期治疗效果需进一步观察。     

自体外周血造血干细胞移植治疗重症天疱疮三例

目的 探讨自体外周血造血干细胞移植治疗天疱疮的疗效及安全性.方法 选择经糖皮质激素、免疫抑制剂等治疗6个月以上病情仍难以控制或病情进展、且出现治疗相关并发症的3例寻常型天疱疮患者进行自体外周血造血干细胞移植治疗,并随访5年以上.3例中男1例,女2例,平均年龄27.3(21～39)岁.造血干细胞的动员方案为环磷酰胺4g/m2、重组人粒细胞集落刺激因子(G-CSF)、利妥昔单抗375 mg/m2;预处理方案为环磷酰胺50 mg·kg-1·d-1连用4d(移植前第6天到移植前第3天)、抗胸腺细胞球蛋白2.5 mg·kg-1·d-1连用4d(移植前第3天至移植当天)、利妥昔单抗600 mg/d于移植当天和移植后第7天静脉滴注.结果 3例天疱疮患者均获得成功植入,平均植活时间白细胞13.3 d(11 ～ 16d),血小板16.3 d(16～ 17d).监测各项免疫指标及相关抗体未见异常,免疫重建良好.随访期间,所有患者无严重并发症,生活质量较前明显提高.结论 自体外周血造血干细胞移植可能是治疗天疱疮有效且安全的新方法之一.     

免疫吸附联合非清髓性CD34+细胞自身移植治疗难治性SLE三例

目的 观察免疫吸附联合非清髓性化疗结合CD34+细胞分选的自体外周血干细胞移植治疗难治性SLE的疗效。方法 难治性SLE 3例，均经肾活检确诊为狼疮性肾炎Ⅳ型，狼疮处于活动期，病情进展，常规治疗无效；应用以葡萄球菌A蛋白作为免疫吸附剂的吸附柱进行免疫吸附，一个疗程共6次，每次吸附血浆3 L；随后采用异环磷酰胺加重组人粒细胞集落刺激因子动员、Baxter CS-3000血细胞分离机采集外周血，获取单一核细胞，通过CD34+细胞分选仪分别得到2.6 × 106/kg、2.1 × 106/kg、2.4 × 106/kg CD34+细胞，采集物中分别含3 × 105/kg、2.1 × 105/kg、2.0 × 105/kg CD3+细胞，预处理为回输前6 d，每日应用氟达拉滨50 mg/d 共5 d，回输前3 d始每日应用抗胸腺细胞球蛋白90 mg/kg共5 d。 结果 ①3例患者吸附后血浆中抗dsDNA、ANA抗体、IgG均明显下降，补体C3明显上升。②3例患者均于移植后2 ~ 3 d获得造血重建。③移植后3例患者临床症状均明显缓解，SLEDAI评分均 < 3分。④移植后6个月，患者血浆中抗dsDNA、ANA抗体均转阴性，补体C3升至正常，尿蛋白转阴性，肾功能恢复正常。结论 移植治疗难治性SLE近期疗效满意。     

在体内具有斑点型抗核抗体染色的患者中抗核基质抗体的意义

结缔组织病患者皮肤病理标本的荧光染色有时表现为表皮细胞的核染色,通常认为是体内结合抗核抗体(ANA)。在体内ANA与高滴度的血清抗-U1 RNP相关,但并不是所有具有抗-U1 RNP抗体的患者都表现有体内ANA现象。在混合结缔组织病(MCTD)、系统性红斑狼疮(SLE)和类风湿性关节炎患者的血清中可检测到抗核基质(nuclear matrix)成分的自身     

自体外周血纯化造血干细胞移植治疗系统性红斑狼疮概况

自体外周血纯化造血干细胞移植为系统性红斑狼疮的治疗开辟了一条新的途径并取得了很好的效果,但尚处于临床研究阶段,对其适应症、干细胞动员、预处理及去除T淋巴细胞方案及远期疗效等仍有争议。但只要我们抓住治疗中的主要矛盾就能有效治疗SLE。     

自体外周造血干细胞移植治疗成人皮肌炎一例

目的 探讨自体外周造血干细胞移植治疗成人皮肌炎的疗效.方法 1例21岁皮肌炎患者接受自体外周造血干细胞移植,随访6年.采用重组人粒细胞集落刺激因子动员外周造血干细胞后,予以环磷酰胺、甲泼尼龙、环孢素预处理,干细胞回输第3天开始使用兔抗人T淋巴细胞免疫球蛋白.观察症状体征、生化指标、造血重建及免疫恢复情况.结果 出院时皮疹明显好转,后逐渐消退;四肢肌力由移植前Ⅳ级转为Ⅴ级并持续至今;移植后肌酸激酶显著下降,但又逐渐恢复到移植前水平;回输当天开始出现白细胞下降,第8天恢复正常造血功能.移植前后免疫功能均正常.结论 对复杂难治性重症皮肌炎,可选择白体外周造血干细胞移植治疗.     

自体造血干细胞移植对SLE患者生活质量的影响

目的探讨自体外周血造血干细胞移植(APBSCT)对系统性红斑狼疮(SLE)患者生活质量的影响。方法对21例住院的SLE患者进行APBSCT治疗。动员方案为环磷酰胺(CTX)4 g/m2,粒细胞集落刺激因子(G-CSF)5μg/(kg.d),4~5天。预处理方案为CTX 50 mg/(kg.d),4天;抗胸腺球蛋白(ATG)15~25 mg/(kg.d),3天。预处理结束后回输采集到的CD34+造血干细胞。采用WHOQOL-BREF中文版,观察并评价移植前后患者的生活质量评分。结果21例患者造血干细胞均成功植入。移植相关的死亡率为0%。WHOQOL-BREF表的五个方面,包括生理、心理、社会关系、环境、总体感觉等在移植后均有明显改善(P<0.05或P<0.01)。结论APBSCT治疗SLE有良好的疗效,患者在移植后生活质量明显改善。     

获得性大疱性表皮松解症先发于SLE

作者报道3例及其他作者报告的2例确诊为获得性大疱性表皮松解症(EBA)之后发生SLE的病例,并检查了另外15例无SLE临床表现的EBA患者的血清狼疮相关抗体.结果提示SLE和EBA之间有明显的关系.在观察和检查的20例确诊为EBA的病例中,9例有狼疮相关抗体,其中5例在EBA确诊后出现SLE的临床表现和自身免疫血清学特征(抗dsDNA抗体、循环抗U1RNP抗体和ANA的阳性率均为100%,抗Ro/SSA抗体为20%;抗Sm抗体为20%),1例在诊断为EBA时即有U1RNP抗体,5例在SLE发病时均出现这种抗体.5例伴有SLE的EBA病人最终均出现了抗     

银屑病患者抗肿瘤坏死因子α治疗前后血清抗核抗体、抗dsDNA抗体及抗ENA抗体的变化

目的：观察银屑病患者接受抗肿瘤坏死因子α制剂治疗后抗核抗体（ANA）、抗dsDNA抗体和抗可提取性核抗原（ENA）抗体的变化。方法回顾分析32例银屑病患者,其中13例使用英夫利西单抗治疗,19例使用依那西普治疗。英夫利西单抗组第0、2、6周各用药1次,此后每隔8周用药,于每次用药前检测患者ANA、抗dsDNA抗体及ENA的情况和临床症状的变化。依那西普组每周用药2次,每3~6个月检测患者ANA、抗dsDNA抗体及ENA的情况和临床症状的变化。采用银屑病皮损面积和严重度指数（PASI）75、疾病活动评分（DAS）28评估临床疗效,间接免疫荧光法检测血清ANA水平,免疫印迹法和ELISA法检测抗dsDNA抗体水平,免疫印迹法检测抗ENA抗体水平。结果32例银屑病患者临床症状有不同程度缓解。32例抗TNF?α治疗的患者中有7例（21.9%）出现自身抗体,其中英夫利西单抗组中4例治疗（8.3±5.1）个月后出现自身抗体,3例ANA阳性,3例ENA阳性;依那西普组中3例治疗（9.0±3.0）个月后出现自身抗体,3例ANA阳性,1例ENA阳性。结论部分银屑病患者接受抗肿瘤坏死因子α制剂治疗后可出现自身抗体。     

Lupus erythematosus and other autoimmune diseases related to statin therapy: a systematic review

BACKGROUND: Statins have been increasingly associated with drug-induced autoimmune reactions, including lupus erythematosus. OBJECTIVE: To identify and determine the clinical and biological characteristics of statin-induced autoimmune reactions. MATERIAL AND METHODS: The MEDLINE database (1966 to September 2005) was used to identify all reported cases of statin-induced autoimmune diseases. The keywords used were statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, adverse effects, autoimmune disease, lupus erythematosus, dermatomyositis and polymyositis. RESULTS: Twenty-eight cases of statin-induced autoimmune diseases have been published so far. Systemic lupus erythematosus was reported in 10 cases, subacute cutaneous lupus erythematosus in three cases, dermatomyositis and polymyositis in 14 cases and lichen planus pemphigoides in one case. Autoimmune hepatitis was observed in two patients with systemic lupus erythematosus. The mean time of exposure before disease onset was 12.8+/-18 months; range 1 month-6 years. Systemic immunosuppressive therapy was required in the majority of cases. In many patients, antinuclear antibodies were still positive many months after clinical recovery. A lethal outcome has been recorded in two patients despite aggressive immunosuppressive therapy. CONCLUSION: Long-term exposure to statins may be associated with drug-induced lupus erythematosus and other autoimmune disorders. Fatal cases have been reported despite early drug discontinuation and aggressive systemic immunosuppressive therapy.     

合并系统性红斑狼疮的尖锐湿疣患者细胞免疫功能检测

目的　研究合并系统性红斑狼疮 (SLE)的尖锐湿疣 (CA)患者细胞免疫功能状态。方法　运用流式细胞术 ,分析了 2 1例合并SLE的CA患者的外周血中T淋巴细胞免疫表型的特点。同时用ELISA法测定了血清中白介素 2(IL 2 )和白介素 12 (IL 12 )的水平变化。结果　 2 1例合并SLE的CA患者外周血中总T(CD3 + ) ,Th(CD4+ )细胞及Th/Ts(CD4+ /CD8+ )均低于正常对照组和单纯CA患者对照组 (P <0 .0 1或P <0 .0 5 ) ,而Ts(CD8+ )的比例显著高于正常对照组和单纯CA患者对照组 (P <0 .0 1)。 2 1例合并SLE的CA患者血清中IL 2和IL 12水平均低于正常对照组和单纯CA患者对照组 (P <0 .0 1)。结论　合并SLE的CA患者的细胞免疫功能受到不同程度的损害 ,并且较单纯CA患者的细胞免疫功能受到更严重的损害。     

Serum levels of BAFF are increased in bullous pemphigoid but not in pemphigus vulgaris

Background BAFF [B‐cell activating factor belonging to the tumour necrosis factor (TNF) family] is a member of the TNF superfamily that regulates B‐lymphocyte proliferation and survival. It has been demonstrated that increased levels of soluble BAFF are associated with systemic autoimmunity in patients with systemic lupus erythematosus, rheumatoid arthritis and Sjögren's syndrome, and in animal models of spontaneous autoimmune diseases. However, the significance of circulating BAFF in autoimmune bullous diseases is unknown. Objectives To examine whether BAFF levels are elevated in the autoimmune blistering diseases pemphigus vulgaris (PV) and bullous pemphigoid (BP). Methods We examined sera obtained from 21 patients with PV, 39 patients with BP and 22 healthy donors. We performed enzyme‐linked immunosorbent assays for soluble BAFF and each disease‐specific antibody: antidesmoglein‐3 antibody for PV and anti‐BP180 antibody for BP. Results Significant elevations of serum BAFF levels were found in the patients with BP, but not with PV. There was apparently no significant association between the serum BAFF levels and titres of anti‐BP180 antibodies in the patients with BP. However, serum BAFF levels tended to be more elevated in patients with a shorter disease duration. There was a tendency that BAFF levels increased before the anti‐BP180 antibody levels increased at the onset of BP and quickly decreased in response to treatment. Conclusions BAFF may be a useful marker for early activation of an autoimmune diathesis and may play a critical role in triggering activation of self‐antigen‐driven autoreactive B cells in BP.     

Interferon response to dipyridamole in lupus erythematosus patients

Studies in patients with autoimmune disorders strongly support a role for interferon (IFN) in the disease process. In the present study we investigated the in vivo production of alpha-IFN in lupus erythematosus patients after stimulation with dipyridamole, recently characterized as an alpha-IFN inducer in mice and humans. Levels of IFN were measured in serum samples from 22 patients with systemic lupus erythematosus (SLE) and 12 patients with discoid lupus erythematosus (DLE) before and 24 h after dipyridamole administration. IFN activity was assayed on human and bovine cells in parallel. Initial serum concentrations of alpha-IFN in SLE patients were markedly elevated. The percentage of DLE positive responders to dipyridamole induction was about twice as high as that found for SLE. Studies of factors responsible for IFN production in lupus erythematosus might result in better understanding of the relationship between DLE and SLE.     

Prevalence and characteristics of anti-single-stranded DNA antibodies in localized scleroderma. Comparison with systemic lupus erythematosus

Prevalence, levels, and immunoglobulin classes of anti-single-stranded DNA antibodies were determined by an enzyme-linked immunosorbent assay in 52 patients with localized scleroderma (33 with morphea, four with generalized morphea, and 15 with linear scleroderma), in 60 healthy controls, and, for comparison, in 31 patients with systemic lupus erythematosus. Localized scleroderma revealed a significant prevalence of anti-single-stranded DNA antibodies, mainly characterized by high levels and IgM and IgA isotypes. Comparison of antibody characteristics in different clinical forms of localized scleroderma showed some significant differences (levels and immunoglobulin isotypes). Comparison with systemic lupus erythematosus showed that frequency, high levels, and IgG isotype of anti-single-stranded DNA antibodies significantly prevailed in systemic lupus erythematosus, while the IgM isotype significantly prevailed in localized scleroderma. However, generalized morphea and linear scleroderma did not significantly differ from systemic lupus erythematosus as regards antibody frequency and prevalence of high antibody levels.     

SLE患者血清弓形体抗体的检测

目的　了解SLE患者血清弓形体IgG抗体的阳性率。 方法　以酶联免疫吸附试验 (ELISA)检测 72例SLE患者血清标本 ,同时以 5 8例健康人血清为对照。结果　SLE患者血清抗弓形体IgG抗体阳性率为 15 .3 %,对照组为3 .45 %,两组比较差异有显著性 (P <0 .0 5 )。结论　SLE患者有继发弓形体病的高度危险。     

Up-regulation of cellular FLICE-inhibitory protein in peripheral blood B lymphocytes in patients with systemic lupus erythematosus is associated with clinical characteristics

Background  Systemic lupus erythematosus (SLE) is an autoimmune disease which is involved in T- and B-lymphocyte–mediated autoimmunity. Apoptosis contributes to the maintenance of lymphocytes homeostasis and the deletion of autoreactive cells in SLE. Although there is evidence that cellular FLICE-inhibitory protein (c-FLIP), an antiapoptosis protein, is increased in human lupus T cells to keep them from apoptosis, but the expression of apoptosis-regulatory protein c-FLIP in SLE B lymphocytes remains unknown.
Aims  To study the expression of c-FLIP in peripheral blood B lymphocytes in SLE patients and to investigate the relationship among the expression of c-FLIP in peripheral blood B lymphocytes in SLE patients, clinical manifestation and the levels of interleukin-4 (IL-4) and IL-10.
Methods  In this study, we detected the expression of c-FLIP in peripheral blood B lymphocytes in SLE patients by flow cytometry and the levels of IL-4 and IL-10 in SLE serum samples by enzyme-linked immunosorbent assay and analysed their relationship with clinical characteristics.
Results  We observed a significantly higher percentage of c-FLIP in peripheral B cells in SLE patients with active disease when compared to inactive ones and healthy controls. And the expression of c-FLIP in lupus peripheral B cells showed positive correlations with SLEDAI, erythrocyte sedimentation rate, C-reactive protein, antinucleosome antibody titre, IL-4, and IL-10, and negative correlation with white blood cell count. Patients with lupus nephritis had higher levels of c-FLIP in peripheral B cells than patients without lupus nephritis.
Conclusion  Our data show that overexpression of c-FLIP is relevant to the activity and severity of SLE. Its overexpression might play a role in preventing B cell from apoptosis in SLE. The cause of c-FLIP overexpression may be due to the increase of IL-4 and IL-10 levels in SLE patients.