红斑狼疮的诊断和治疗

红斑狼疮(LE)是自身免疫介导的、以炎症为表现的结缔组织疾病，常累及多个脏器和器官，临床表现较为复杂而多变．常以缓解和复发交替出现，病程呈慢性迁延．多见于女性。有时与其他结缔组织病如皮肌炎、硬皮病等重叠出现。LE是一个病谱疾病，病谱的一端为DLE，病变主要限于皮肤，另一端为SLE伴弥漫增殖性狼疮性肾炎。中间有很多亚型，如DDLE、LET、深在性红斑狼疮、SCLE、新生儿红斑狼疮、ANA阴性的SLE等。     

抗核小体抗体检测在系统性红斑狼疮中的临床应用

目的探讨抗核小体抗体(AnuA)在系统性红斑狼疮(SLE)中的临床应用。方法采用酶联免疫吸附法(ELISA)检测187例SLE及84例其他风湿性疾病患者血清AnuA和抗dsDNA抗体水平,采用免疫印迹法检测抗Sm抗体。结果 AnuA诊断SLE的敏感性和特异性分别为72.19%和97.62%,其敏感性显著高于抗dsDNA抗体、抗Sm抗体(P<0.05),其特异性与抗dsDNA抗体、抗Sm抗体差异无统计学意义(P>0.05);联合检测AnuA、抗dsDNA抗体、抗Sm抗体诊断SLE的敏感性达95.72%。SLE患者AnuA阳性组与阴性组相比,阳性组患者口腔溃疡、关节疼痛发生率更高,24h尿蛋白异常和补体C3降低(P<0.05)。结论 AnuA对SLE有较高敏感性和特异性,是诊断SLE最有价值的指标之一;联合检测AnuA、抗dsDNA抗体、抗Sm抗体可提高SLE的诊断;AnuA可能与SLE疾病活动性相关。     

系统性红斑狼疮患者外周血单一核细胞CCR6、CCR8趋化因子受体mRNA的表达

目的:探讨趋化因子受体CCR6及CCR8在系统性红斑狼疮(SLE)患者外周血单一核细胞(PBMC)中的表达及与疾病的相关性.方法:收集93例确诊的SLE患者和30例正常对照者的PBMC,提取RNA.应用RT-PCR方法检测研究对象CCR6、CCR8 mRNA表达水平.记录患者临床表现及实验室检查结果.结果:①CCR6 mRNA在PBMC中表达水平:活动期组(0.985±0.257)与对照组(0.229±0.041)相比,两者差异有统计学意义(t=2.910,P=0.006).活动期组与非活动期组(0.306±0.034)、非活动期组与对照组、患者组(0.641±0.179)与对照组,3组间差异均无统计学意义(P>0.05).CCR8 mRNA在PBMC中表达水平:活动期组(0.703±0.285)与非活动期组(0.219±0.031)及对照组(0.120±0.018)间比较,差异无统计学意义(P>0.05);非活动期组与对照组、患者组(0.549±0.663)与对照组,两组间差异无统计学意义(P>0.05).②患者组CCR6 mRNA水平与疾病活动度评分关系:SLE患者组PBMC中CCR6 mRNA表达水平与SLE疾病活动程度指数(SLEDAI)分别作直线相关性分析,CCR6 mRNA水平与SLEDAI(r=0.457,t=4.513,P<0.001)呈正相关.③患者分为两个亚组:具有某些临床表现的与不具临床表现的CCR6mRNA及CCR8 mRNA表达.差异无统计学意义.结论:CCR6 mRNA表达水平在活动期SLE患者比非活动期及对照组增高,与SLEDAI呈正相关.CCR8 mRNA表达水平在SLE患者组与正常对照组差异无统计学意义.CCR6可能参与SLE的发生.     

系统性红斑狼疮患者血清中α-干扰素测定的临床意义

目的:探讨血清中α-干扰素(IFN-α)水平变化在系统性红斑狼疮(SLE)及狼疮性肾炎(LN)中的临床意义。方法:采用ELISA法对36例SLE患者(含29例LN患者)和10名正常对照者进行血清IFN-α水平检测,比较分析其与SLE活动指数(SLEDAI),肾脏组织病理活动指数(AI),抗dsDNA,补体C3,白细胞计数的相关性。结果:SLE患者血清IFN-α水平活动期为284.2pg/mL,静止期为160.3pg/mL,明显高于正常对照组121.8pg/mL(P<0.05),并且活动期高于静止期(P<0.01)。血清IFN-α水平与SLEDAI呈正相关(r=0.6101,P<0.05),AI≥8的患者为264.3pg/mL,明显高于AI<8患者的202.4pg/mL(P<0.01)。结论:检测SLE血清中IFN-α水平可作为活动敏感指标之一。     

系统性红斑狼疮患者136例疾病活动性的评价

目的:探讨系统性红斑狼疮(SLE)患者疾病活动指数(SLEDAI)的价值。方法:以SLEDAI作为评价SLE患者疾病活动性的标准。结果:136例SLE患者SLEDAI得分最小为0分,最大为52分,平均(12.88±10.58)分,男女相比差异无显著性(P>0.05)。抗核抗体(ANA)、抗Sm抗体与SLEDAI无相关性。农村患者与城市患者SLEDAI相比,差异有显著性(P<0.05)。SLEDAI与患者住院天数相关(相关系数r=0.477,P<0.05)。结论:SLEDAI为一种较好的评价SLE患者疾病活动性的方法,是患者治疗、预后评价的有用指标。     

系统性红斑狼疮患者血清5-HT,IL-12水平及临床意义探讨

目的检测系统性红斑狼疮(SLE)患者血清5-羟色胺(5-HT)、IL-12的水平,探讨其与疾病活动程度的相关性。方法选取SLE患者49例,其中活动期21例,稳定期28例,另选取健康对照30例,用固相夹心ELISA法测定血清5-HT水平,双抗夹心ELISA法测定血清IL-12水平。结果 SLE患者组血清5-HT水平较对照组低(P0.05),而活动期组又较稳定期组低(P0.5);5-HT同病情活动程度呈负相关(P0.05)。SLE患者组血清IL-12水平低于对照组(P0.05),但活动期和稳定期患者间差异无显著性;5-HT水平同IL-12水平呈正相关(P0.05)。结论 5-HT可能参与了SLE的发生和发展,同IL-12水平及病情活动程度密切相关。     

BLyS及其受体BAFF-R在SLE患者中的表达及与SLEDAI和血清IgG的相关性研究

目的:通过在基因和蛋白水平上检测系统性红斑狼疮(SLE)患者BLyS及其受体BAFF-R的表达水平,探讨BLyS及BAFF-R与SLE发病机制的相关性。方法:实时荧光定量聚合酶链反应(Realtime PCR)检测60例SLE患者(其中病情活动期34例,稳定期26例)、50例健康人群外周血单个核细胞(PBMC)的BLyS mRNA、BAFF-R mRNA的表达水平,ELISA方法检测其血清BLyS的表达,并分析其与SLE活动指数(SLEDAI)、血清免疫球蛋白IgG的相关性。结果:SLE患者PBMC中BLyS、BAFF-R mRNA及血清中BLyS蛋白表达水平均明显高于健康对照组(t值分别为14.02、14.6、9.56,P值均0.01);活动期BLyS mRNA及BLyS蛋白表达水平明显高于稳定期(t值分别为2.26、3.96,P值均0.05),BAFF-R mRNA表达在活动期和稳定期之间没有差别(t=1.49,P0.05)。SLE患者BLyS mRNA及BLyS蛋白水平均与SLEDAI积分和血清IgG水平呈正相关(P值均0.01),BAFF-R mRNA水平则与SLEDAI、IgG均无相关性(P值均0.05)。结论:SLE患者BLyS mRNA、BAFF-R mRNA、BLyS蛋白表达水平升高,BLyS在一定程度上反映了病情的活动,表明BLyS及其受体可能参与SLE的发生和发展,并为监控SLE的病情和治疗效果提供了新的辅助方法。     

汉族人抗核小体抗体与系统性红斑狼疮临床特征及其活动性的相关性

目的分析抗核小体抗体(AnuA)与系统性红斑狼疮(SLE)患者临床特征及其活动性的相关性。方法采用回顾性研究并用调查表的形式收集694例AnuA阳性患者临床资料,并与733例An-uA阴性病人进行比较分析。结果 AnuA与蝶形红斑、光敏感、关节炎、心包炎及狼疮性肾炎的发生相关(P<0.05);AnuA阳性可伴有其他自身抗体及免疫学指标异常出现;AnuA阳性与肾脏损害指标血尿、蛋白尿、管型尿及尿素氮的发生率明显相关(P<0.05);AnuA阳性与系统性红斑狼疮疾病活动性指数(SLEDA I)相关(P<0.05)。结论 AnuA可能是SLE的又一标志性抗体,其检测可用于疾病的早期诊断,有助于SLE疾病活动度、严重程度及狼疮肾炎(lupus nephritis,LN)的判断。     

系统性红斑狼疮血清干扰素诱导蛋白10的检测及其意义

目的:检测系统性红斑狼疮(SLE)患者血清干扰素诱导蛋白10(IP-10)水平,并探讨其临床意义.方法:采用ELISA法检测58例SLE患者及40名正常对照者血清IP-10,比较分析其与SLE病情活动指数(SLEDAI)、肾损害、抗dsDNA、补体C3和白细胞计数的相关性.结果:SLE患者血清IP-10水平明显高于正常对照组(P＜0.01),并且活动期高于静止期(P＜0.01),肾损组高于无肾损组.血清IP-10水平与SLEDAI(P＜0.01)、抗dsDNA抗体滴度对数值呈正相关(P＜0.05),与C3(P＜0.01)、白细胞计数(P＜0.05)呈负相关.结论:检测血清IP-10水平有可能作为狼疮活动的敏感指标之一.     

可诱导共刺激分子在系统性红斑狼疮患者外周血T淋巴细胞的表达

目的 探讨可诱导共刺激分子(ICOS)在系统性红斑狼疮(SLE)患者外周血T淋巴细胞的表达。方法 应用双色荧光抗体染色技术经流式细胞仪检测了33例SLE患者和16例正常人对照者外周血中T淋巴细胞表面ICOS的自然表达水平,同时收集SLE患者的实验室检查指标,并用SLE疾病活动指数(SLEDAI)来判定SLE患者疾病活动程度,比较分析不同组别SLE患者ICOS表达水平与SLEDAI的相关性。结果 活动期SLE组T淋巴细胞ICOS表达水平明显高于正常人对照组(P<0.01)和非活动期SLE组(P<0.01),非活动期SLE组与正常人对照组T淋巴细胞ICOS表达水平则差异无统计学意义(P>0.05)。活动期组与非活动期组SLE患者T淋巴细胞ICOS表达水平均与SLEDAI呈显著正相关(r=0.71,P=0.001、r=0.56,P=0.03)。结论 活动期SLE患者T淋巴细胞ICOS表达增高,ICOS可能与SLE的发病机制有关。     

Phototests in Patients with Various Forms of Lupus Erythematosus

Responses to ultraviolet B (UVB; 290-320 nm) were tested in 227 patients with main forms of lupus erythematosus (LE): discoid LE (DLE), discoid disseminated LE (DDLE), systemic LE (SLE), and subacute cutaneous LE (SCLE). Four parameters were evaluated: minimal erythema dose (MED), its distribution, persistence of erythema, and photoreproduction of lesions. Patients with LE differed considerably from controls in their UVB reactivity. In addition, there were significant differences between various LE forms, even after a single UV exposure. Lowered MED in comparison to controls was observed most frequently in SLE patients (64.4%) and least frequently in DLE patients (32.1%). Prolonged persistence of erythema induced by 1-2 MED was a constant finding in SCLE. In SLE and DDLE, it was observed in more than 80% of patients, and in DLE in 56.7% of examined cases. Photoreproduction of lesions after single UVB exposure was observed most frequently in SCLE (62.5%) and only in 10% of DLE patients.     

The presence of anti–basement membrane zone antibodies in the sera of patients with non–bullous lupus erythematosus

We performed indirect immunofluorescence (IF) studies using 1 mol/1 sodium chloride split skin to determine whether or not a positive IF is specific to patients with bullous lupus erythematosus (LE). We examined the sera from 21 patients with systemic LE (SLE), three of which were obtained from two SLE patients and one subacute cutaneous LE (SCLE) patient with bullous eruptions. As a comparison, we also studied the sera from patients with discoid LE (DLE,n= 7). SCLE (n= 1), systemic sclerosis (SSc, n= 20), bullous pemphigoid (n= 2) and normal individuals (n= 10). Sera from 16 SLE, four DLE and two SSc revealed a linear deposition of IgG isotype antibody at the epidermal side and/or the dermal side on indirect IF of split skin. The sera from three patients with bullous eruption and from 12 patients of SLE, SCLE, DLE without bullous eruption or SSc were further analysed by immunoblotting using five defined antigens, i.e, dermal extract, epidermal extract, three fusion proteins of 230 kDa bullous pemphigoid antigen (BPAG), 180 kDa BPAG, and human epidermolysis bullosa acquisita (EBA) antigen. Two SLE sera as well as one of the SCLE and the DLE serum reacted with 230 kDa BPAG in epidermal extract, and one of the SCLE and the DLE serum also reacted with the fusion protein of 180 kDa BPAG, No serum reacted with the dermal extract or the fusion protein of 230 kDa BPAG or EBA antigen. There was no consistent correlation between split–skin IF results and immunoblotting results. These results may suggest that even non–bullous LE patients often have autoantibodies to the basement membrane zone antigens, most of which are less pathogenic. Although we rarely examine the sera from non–bullous LE patients, we should keep this phenomenon in mind to avoid overestimating the results of split–skin test and immunoblotting.     

Tyrosine kinase 2 and interferon regulatory factor 5 polymorphisms are associated with discoid and subacute cutaneous lupus erythematosus

Please cite this paper as: Tyrosine kinase 2 and interferon regulatory factor 5 polymorphisms are associated with discoid and subacute cutaneous lupus erythematosus. Experimental Dermatology 2010; 19: 123–131. Abstract: Lupus erythematosus (LE) is a heterogeneous disease ranging from skin‐restricted manifestations to a progressive multisystem disease. The specific skin lesions include chronic cutaneous, subacute cutaneous and acute cutaneous LE. Both genetic and environmental factors are involved in the development of LE. However, reports on the genetic background of cutaneous lupus erythematosus (CLE) forms, namely discoid (DLE) and subacute cutaneous lupus erythematosus (SCLE), are sparse. We investigated whether the known systemic LE (SLE) susceptibility genes also predispose to CLE. Altogether, 219 Finnish patients with DLE or SCLE and 356 healthy controls were recruited. Single nucleotide polymorphisms tagging reported risk genes were genotyped. Tyrosine kinase 2 (TYK2) rs2304256 was associated with increased risk of DLE (P = 0.012, OR = 1.47, 95% CI = 1.01–1.98). Expression of TYK2 was demonstrated by immunohistochemistry in macrophage‐like cells and neutrophils and interferon regulatory factor 5 (IRF5) in macrophage‐ and fibroblast‐like cells of DLE, SCLE and SLE skin. IRF5 rs10954213 showed association with DLE (P = 0.017, OR = 1.40, 95% CI = 1.06–1.86) and SCLE (P = 0.022, OR = 1.87, 95% CI = 1.09–3.21). A haplotype of cytotoxic T‐lymphocyte‐associated protein 4 (CTLA4) showed association with DLE (P = 0.0065, OR = 2.51, 95% CI = 1.25–5.04). Our results show that the TYK2, IRF5 and CTLA4 genes previously associated with SLE also confer risk for DLE and SCLE, suggesting that different LE subphenotypes may share pathogenetic pathways.     

Different patterns of soluble adhesion molecules in systemic and cutaneous lupus erythematosus

Abstract Circulating isoforms of cellular adhesion molecules (CAMs) have been described recently, and elevated levels of certain sCAMs have been reported in various inflammatory diseases such as systemic lupus erythematosus (SLE). There are previously no reports on sCAMs in cutaneous LE. Sera from 61 patients with LE: systemic (SLE: n= 24), chronic cutaneous (discoid LE, DLE: n= 19) or subacute cutaneous (SCLE: n= 8), chronic biologically false positive (CBFP) reactors for syphilis (n= 10) and 32 controls were examined for sICAM-1, sVCAM-l and sE-Se-lectin with specific ELISA kits. Protocol forms were reviewed. We found significantly elevated levels of sE-Selectin in patients with DLE and widespread cutaneous symptoms, and a correlation between active cutaneous disease as well as polymorphous light eruption (PLE) and elevated levels of sE-Selectin. In contrast, patients with systemic LE did not have elevated levels of sE-Selectin, but in concordance with earlier reports, sICAM-1 and sVCAM-l levels were elevated compared to controls in SLE. as well as in SCLE patients, which has not been reported previously. Since activated endothelial cells are the only source for E-Selcetin, the elevated sE-Selectin level in patients with widespread and active cutaneous disease suggests a more important role for endothelial cells in the pathogenesis of cutaneous LE than previously assumed.     

Epidemiology of cutaneous lupus erythematosus in a tertiary referral centre in Singapore

The aim of this retrospective study was to investigate the epidemiology, yield of investigations and proportion of patients who develop systemic lupus erythematosus (SLE) among the subsets of cutaneous lupus erythematosus (LE) in the Singapore Asian population. One hundred and twenty-five patients were diagnosed with cutaneous LE on clinico-pathological correlation, of which 73 had discoid lupus erythematosus (DLE), eight had subacute cutaneous LE (SCLE), 22 had acute LE lesions and the remainder had other less common forms of cutaneous LE. Histology was consistent with LE in 94.4% and suggestive in 4.8%. Direct immunofluorescence was positive in 61% of DLE, 86% of SCLE and 80% of acute LE cases. Antinuclear antibody (ANA) was present in the majority of acute LE (85%) and SCLE (88%) but only in 25% of DLE. Eight patients (11%) presenting with DLE had definite SLE at first presentation and two (2.7%) subsequently several months later. Of these patients, six had only mucocutaneous and serological criteria but two had major organ involvement. Five SCLE patients (63%) fulfilled the criteria for SLE, including two with major organ involvement.     

The phenotypic profile of dermatomyositis and lupus erythematosus: a comparative analysis

Background: The mechanisms which regulate cutaneous inflammation in the setting of collagen vascular disease have been a topic of recent interest; emphasis has been placed on type I interferon‐associated recruitment of CXCR3+ lymphocytes in dermatomyositis (DM). Methods: On a total of 42 biopsies from patients with DM, systemic lupus erythematosus (SLE), discoid lupus erythematosus (DLE) and subacute cutaneous lupus erythematosus (SCLE) comprehensive phenotypic studies were performed to explore the practical value of phenotypic analysis in the subclassification of lesions of collagen vascular disease. Results: The infiltrate in DM was of mild intensity compared to lupus erythematosus (LE). The dominant mononuclear cell in DM exhibited a CD4/CXCR3‐positive phenotype while biopsies of SLE typically showed a dearth of CXCR3‐positive cells. CD8 and CD20 lymphocytes were greatest in SLE and DLE, respectively. CD123 plasmacytoid dendritic cells, seen in most cases, were most frequent in cases of SCLE; CD83 expression was minimal. Endothelial MXA expression was a characteristic feature of DM. CD123 and MXA expression within inflammatory cells and keratinocytes was most conspicuous in areas of interface injury. Cutaneous lymphocyte antigen (CLA) expression was diminished in the dermal infiltrate in most cases of DM and LE. T regulatory cells never exceeded 15% of the infiltrate and were the least in the setting of DM and LE. Conclusions: An interferon‐α‐inducible cytokine milieu is common in SLE, DLE, SCLE and DM. In addition, there are phenotypic differences as alluded to above that may be of some practical value in separating these distinctive subsets. Features not previously emphasized such as MXA endothelial cell staining in DM and the lack of staining for CD83 and CLA in lesions of collagen vascular disease may be of diagnostic value. Magro CM, Segal JP, Crowson AN, Chadwick P. The phenotypic profile of dermatomyositis and lupus erythematosus: a comparative analysis.     

The interferon-regulated gene signature is elevated in subacute cutaneous lupus erythematosus and discoid lupus erythematosus and correlates with the cutaneous lupus area and severity index score

Background There is increased expression of type I interferon (IFN)‐regulated proteins in the blood and target tissues of patients with cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE). Patients with SLE have increased IFN‐regulated gene expression pointing towards a possible underlying genetic defect. Objectives To determine expression levels of five type I IFN‐regulated genes that are highly expressed in SLE in the peripheral blood of patients with CLE and to correlate the expression levels with cutaneous disease activity. Methods Peripheral blood was obtained from 10 healthy controls and 30 patients with CLE, including eight with concomitant SLE. Total RNA was extracted and reverse transcribed into complementary DNA. Gene expression levels were measured by real‐time polymerase chain reaction. Gene expression was normalized to GAPDH, standardized to healthy controls and then summed to calculate an IFN score for each patient. Disease activity was assessed with the Cutaneous Lupus Area and Severity Index (CLASI). Results Patients with subacute CLE (SCLE) and discoid lupus erythematosus (DLE) had elevated IFN scores compared with healthy controls regardless of concomitant SLE (P < 0·01 with SLE and P < 0·05 without SLE). There was no difference between patients with tumid lupus erythematosus (TLE) and healthy controls. The IFN score correlated with CLASI scores (Spearman’s rho = 0·55, P = 0·0017). Conclusions Patients with SCLE and DLE have an IFN signature, as seen in SLE. The level of gene expression correlates with cutaneous disease activity. These findings support a shared pathogenesis between SLE and some subtypes of CLE.     

Comparative analysis of subacute cutaneous lupus erythematosus and chronic cutaneous lupus erythematosus: clinical and immunological study of 270 patients

Background Lupus erythematosus (LE) is a chronic, autoimmune disease resulting from an interaction of genetic, environmental and hormonal factors and characterized by a spectrum of clinical forms with variable evolution from a localized cutaneous form to a life‐threatening systemic form. Objective To analyse and compare the prevalence and characteristics of the main clinical and immunological manifestations of subacute cutaneous LE (SCLE) and chronic CLE (CCLE). Methods A total of 270 patients with CLE (112 patients with SCLE and 158 patients with CCLE) were studied retrospectively. The clinical and serological characteristics of all the patients were collected in a chart review. Results The patients with SCLE had a higher prevalence of annular and papulosquamous lesions, Raynaud phenomenon, mucous membrane ulcers, malar rashes, photosensitivity, vasculitis and a lower frequency of discoid lesions and alopecia compared with patients with CCLE. Patients with SCLE had a higher prevalence of arthralgias (P < 0·001), xerophthalmia (P = 0·045), arthritis (P < 0·001), nephropathy (P = 0·003) and systemic LE (SLE) (P < 0·001) compared with patients with CCLE. Patients with SCLE also had a higher frequency of laboratory and serological abnormalities than patients with CCLE. Generalized discoid LE (DLE) was associated with a higher prevalence of photosensitivity (P < 0·001), panniculitis (P = 0·009) and SLE (P = 0·003) than localized DLE. In patients with SCLE and those with CCLE, photosensitivity, arthralgias, arthritis, nephropathy and xerophthalmia were associated with SLE. In patients with SCLE, significant correlations existed between clinical and immunological data. Conclusions In our series, differences in the expression of CCLE and SCLE were found with respect to the distribution and type of lesions, systemic features and immunological findings.     

SLE患者外周血造血干/祖细胞的检测及临床意义

目的 探讨SLE患者外周血CD34+造血干/祖细胞（HSC/HPC）数目与CD34膜表达的变化。方法 采用异硫氰酸荧光素标记抗体,以流式细胞仪检测30例SLE患者和14例正常人外周血CD34+ HSC/HPC,分析CD34+ HSC/HPC细胞占全部淋巴细胞的百分比和CD34平均荧光强度,并结合临床资料进行相关性分析。结果 活动期和稳定期SLE患者外周血CD34+ HSC/HPC细胞占淋巴细胞百分比分别为（0.15 ± 0.10）%和（0.09 ± 0.07）%,低于正常人对照组［（0.37 ± 0.17）%,F = 17.18,P < 0.01］,而活动期和稳定期SLE患者差异无统计学意义（t = 1.51,P > 0.05）;活动期SLE患者外周血CD34抗原的平均荧光强度为41.35 ± 19.24,高于正常人对照组（27.43 ± 7.57,F = 3.13,P < 0.05）,而稳定期SLE患者与正常人对照组差异无统计学意义（F = 3.13,P > 0.05）。外周血CD34+ HSC/HPC细胞百分比与血清IgG水平呈负相关（r = -0.588,P < 0.01）,与SLE疾病活动指数（SLEDAI）、补体、抗dsDNA抗体、抗C1q抗体、抗核小体抗体等无统计学相关性。结论 SLE患者外周血CD34+ HSC/HPC细胞数减少,并且CD34抗原表达增加,提示SLE患者HSC/HPC功能存在异常,可能参与SLE的发病。     

Matrix metalloproteinases as mediators of tissue injury in different forms of cutaneous lupus erythematosus

Background Matrix metalloproteinases (MMPs) contribute to tissue destruction, regeneration, inflammation and apoptosis and several of them are upregulated by ultraviolet (UV) radiation in skin. Although some MMPs associate with organ manifestations of systemic lupus erythematosus (SLE), their role in cutaneous lupus erythematosus (LE) is elusive. Objectives Our aim was to evaluate the expression of MMPs in SLE, subacute cutaneous LE (SCLE) and discoid LE (DLE) skin lesions and their relation to apoptosis and epidermal changes. Methods Lesional skin biopsies from 20 patients with SLE, 20 with DLE and 17 with SCLE, and from UVA/UVB‐photoprovoked skin of healthy volunteers were immunostained using antibodies to multiple MMPs and tissue inhibitors of metalloproteinases (TIMPs). The TUNEL (terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate nick end labelling) method was used for detection of apoptosis. Results MMP‐3, ‐10, ‐19 and ‐26 were abundantly expressed by keratinocytes in SLE, DLE and SCLE skin samples. MMP‐7 was detected in keratinocytes in regions of oedema and vacuolization especially in SLE and SCLE, while MMP‐14 was only occasionally observed in keratinocytes. Photoprovocation did not induce MMP‐10 or ‐26 expression in skin of healthy volunteers. Epithelial TIMP‐1 expression was low while occasional positive fibroblasts were seen in the dermis. TIMP‐3 was abundantly expressed in the epidermis, endothelial cells and macrophages. Conclusions Different subtypes of cutaneous LE are fairly similar in their MMP expression profile. MMP‐3 and ‐10 mediate both epidermal changes and dermal tissue remodelling but are not present in lymphocytes. Low expression of TIMP‐1 suggests that lupus skin is characterized by proteolytic events, and targeted action using selective MMP inhibitors may reduce lupus‐induced damage in inflamed tissues.