结缔组织疾病

20140804 Blimp1-BCMA调控浆细胞功能在系统性红斑狼疮发病中的意义/彭学标（南方医科大学南方医院皮肤科）,欧丽娜∥中华皮肤科杂志.-2013,46（9）.-617-620 采用EMSA和CHIP证实Blimp1对B细胞成熟抗原（BCMA）的调控作用,并用实时定量PCR检测MRL/lpr狼疮鼠与正常鼠脾脏和淋巴结中Blimp1mRNA的表达。结果：Blimp1能与BCMA基因启动子相结合;狼疮鼠脾脏Blimpl mRNA的相对表达水平高于正常对照组,狼疮鼠组淋巴结中Blimpl mRNA的相对表达水平也高于正常对照。表明BCMA可能是Blimpl的靶基因,Blimpl可直接调控BCMA表达,在维持浆细胞存活及抗体分泌中发挥作用。     

mTORC1信号通路在狼疮鼠体内的表达及意义

目的：检测mTORC1信号通路在系统性红斑狼疮鼠体内的表达,探讨其在系统性红斑狼疮发病中的作用。方法： 研究对象为6只B6.MRL/lpr狼疮小鼠和6只C57正常小鼠。RT-PCR和Western blot检测肾脏组织Akt、mTOR、p70S6K、IL-17 mRNA和蛋白的表达。细胞内染色流式细胞术检测脾脏Th17淋巴细胞亚群比例。结果： 狼疮鼠组Akt、mTOR、p70S6K、IL-17 mRNA、磷酸化蛋白表达水平高于对照组（P<0.05）;狼疮鼠组的Th17细胞占CD4+T细胞的比例高于正常对照组（P<0.05）。结论： mTORC1（Akt-mTOR-p70S6K）信号通路在SLE的发病中起着重要作用。     

雷公藤多苷对狼疮鼠肝肾组织中11β-羟基类固醇脱氢酶的影响

目的: 明确雷公藤多苷对MRL/lpr狼疮小鼠肝脏组织中11β-羟基类固醇脱氢酶1（11β-HSD1）和肾组织中11β-羟基类固醇脱氢酶2（11β-HSD2）表达的影响。方法: 将14只MRL/lpr狼疮鼠随机分为实验组和对照组,实验组8只给予雷公藤多苷15 mg/kg灌胃,每天1次,连续15天,其余6只作为空白对照。免疫组化、RT-PCR分别检测11β-HSD的IOD值和mRNA的表达。结果: 实验组中11β-HSD1的IOD和mRNA分别为1.03±0.05和1.55±0.09,高于对照组的0.83±0.04和1.23±0.07,（P<0.05）;实验组中11β-HSD2的IOD和mRNA为0.86±0.06和1.10±0.04低于对照组中的0.90±0.05和1.15±0.06）,差异无统计学意义（P>0.05）。结论: 雷公藤多苷可诱导肝脏中11β-HSD1的表达。     

骨髓间充质干细胞对狼疮鼠B淋巴细胞AKT/GSK3β信号通路影响的检测

目的:研究骨髓间充质干细胞(BM-MSC)对MRL/lpr狼疮鼠B淋巴细胞活化及AKT/GSK3β信号通路的影响。方法:从C57/BL6小鼠骨髓细胞中分离培养BM-MSC,用不同剂量的BM-MSC移植治疗MRL/lpr狼疮鼠,4周后免疫磁珠分选出B淋巴细胞,流式细胞仪检测细胞周期,Western Blot检测AKT/GSK3β信号通路相关蛋白表达变化。结果:狼疮鼠B淋巴细胞体外刺激后S期比例明显增多,中、高剂量BM-MSC移植治疗能降低刺激后的狼疮鼠B淋巴细胞S期比例,并增加细胞周期蛋白p27Kip1的表达。BM-MSC移植治疗能抑制B淋巴细胞phospho-AKTThr308及phospho-GSK3βSer9的表达。结论:中、高剂量BM-MSC移植治疗能抑制狼疮鼠B淋巴细胞的异常活化,并抑制AKT/GSK3β信号通路的异常活化。     

单核细胞趋化蛋白-1 DNA疫苗治疗姥鲛烷诱导BALB/c狼疮鼠模型的实验研究

目的 应用单核细胞趋化蛋白-1（MCP-1）基因片段的DNA疫苗免疫姥鲛烷诱导的BALB/c狼疮鼠模型,研究MCP-1 DNA疫苗对狼疮鼠模型的免疫抑制作用以及对肾脏的保护效果。方法 BALB/c小鼠随机分为4组：狼疮鼠模型组、疫苗组、空质粒组、正常对照组。制备编码MCP-1基因片段的DNA疫苗,接种于疫苗组。测定各组小鼠体质量、24 h尿蛋白定量,ELISA法测定血清MCP-1抗原和抗体水平,免疫荧光法检测血清ANA;HE染色光镜下观察小鼠肾脏病理变化,免疫组化检测MCP-1、CD68在肾脏内的表达。结果 24周时狼疮鼠模型组、疫苗组、空质粒组和正常对照组间体质量和24 h尿蛋白定量差异有统计学意义,F值分别为20.31,6.74,P值均 < 0.05,LSD检验示疫苗组与狼疮鼠模型组和空质粒组之间差异有统计学意义（P值均 < 0.01）。狼疮鼠模型组、疫苗组、空质粒组和正常对照组血清MCP-1抗原水平分别为（572.6 ± 58.55）、（169.52 ± 28.71）、（601.98 ± 83.43）和（61.11 ± 66.12） ng/L,差异有统计学意义（F = 143.09,P < 0.05）,LSD检验示疫苗组与狼疮鼠模型组、空质粒组之间差异有统计学意义（P < 0.01）;四组的血清MCP-1抗体水平分别为（357.88 ± 82.41）、（770.14 ± 220.91）、（294.25 ± 177.22）和（129.73 ± 168.24） ng/L,方差分析示F = 15.81,P < 0.01,LSD检验示疫苗组与狼疮鼠模型组、空质粒组和正常对照组之间差异有统计学意义。ANA抗体阳性率四组间差异无统计学意义。疫苗组和正常对照组与狼疮鼠模型组和空质粒组比较,肾脏损伤明显减轻,肾脏内MCP-1和CD68阳性细胞明显减少。结论 MCP-1质粒DNA疫苗能够有效抑制狼疮鼠模型血清中MCP-1抗原表达,并诱导MCP-1抗体水平升高。     

滋阴清热药对狼疮鼠肾组织自噬基因atg16L1和细胞焦亡炎症因子的影响

目的探讨滋阴清热药对狼疮鼠肾组织自噬基因atg16L1和细胞焦亡炎症因子的影响。方法以滋阴清热方干预狼疮鼠,免疫组织化学方法观察自噬基因atg16L1肾组织中的组织形态,定量PCR检测atg16L1基因表达,同时检测肾组织细胞焦亡上下游炎症因子Caspase-1,IL-1β以及足细胞靶抗原Nephrin,Actinin4。结果滋阴清热药能提高狼疮模型鼠组肾组织自噬基因atg16L1的表达(P0.01),降低细胞焦亡炎症因子IL-1β(P0.01)以及足细胞靶抗原Nephrin表达(P0.05)。结论滋阴清热药能调控狼疮鼠肾组织自噬基因atg16L1,减轻免疫炎症和器官损害。     

全淋巴区电子线照射治疗MRL/lpr狼疮小鼠疗效观察与机制探讨

【摘要】 目的 观察全淋巴区电子线照射治疗MRL/lpr狼疮小鼠的疗效,并探讨其与调节性T细胞的关系。 方法 将18只4月龄的MRL/lpr小鼠随机分为阴性对照组、放射治疗组、地塞米松治疗组,每组6只,雌雄各半,阴性对照组予生理氯化钠溶液0.5 ml腹腔注射每日1次,连续2周;放射治疗组全身淋巴结予电子线照射,2 Gy/d,每周5次,连续2周;地塞米松治疗组予地塞米松1 mg/kg腹腔注射每日1次,连续2周,实验结束后2周测各项指标。考马斯亮蓝法测24 h尿蛋白,ELISA法检测各组小鼠ANA及抗dsDNA抗体水平,直接免疫荧光法观察各组小鼠IgG抗体在肾脏的沉积情况,PAS染色法观察各组小鼠的肾脏情况,流式细胞仪测定各组小鼠脾脏细胞中调节性T细胞所占比例。用SPSS11.5统计软件进行多样本组间单因素方差。 结果 放射治疗组小鼠24 h尿蛋白含量为（3.33 ± 0.17） mg,阴性对照组为（3.97 ± 0.33） mg,两组比较,P < 0.05。放射治疗组小鼠血清抗核抗体ANA水平为（275.12 ± 30.18） U/ml,抗小鼠dsDNA抗体为（455.74 ± 43.38） IU/ml;阴性对照组小鼠分别为（434.82 ± 36.63） U/ml和（956.78 ± 37.69） IU/ml,两组比较,均为P < 0.05。放射治疗组与地塞米松治疗组小鼠肾小球内IgG沉积较阴性对照组减少,强度较弱,放射治疗组、地塞米松治疗组两组无明显差异。PAS染色可见放射治疗组与地塞米松治疗组肾脏病变较阴性对照组减轻,放射治疗组、地塞米松治疗组两组无明显差异。流式细胞仪检测显示,放射治疗组小鼠调节性T细胞所占比例为（1.08 ± 0.52）%,地塞米松治疗组为（1.18 ± 0.60）%,阴性对照组为（0.38 ± 0.14）%,放射治疗组、地塞米松治疗组两组的调节性T细胞所占比例较阴性对照组升高（P < 0.05）。 结论 全淋巴区电子线照射能降低MRL/lpr狼疮小鼠尿蛋白、血清抗核抗体、双链DNA抗体水平,对肾脏病理改变亦有恢复作用,其机制可能与提高体内调节性T细胞的比例有关。     

A20蛋白水平影响狼疮模型小鼠TLR2、4-p38MAPK/NF-kB信号通路的初步研究

目的探讨PBMC中高水平的A20(TNFAIP3)蛋白能否抑制TLR2、4-p38MAPK/NF-κB信号通路并缓解SLE小鼠的炎症反应。方法观察MRL/lpr小鼠瑞香素(Daphnetin)处理组一般情况和生存期,检测其尿蛋白含量;检测血清中BUN、anti-dsDNA IgG、IL-6和TNF-α水平;检测PBMC裂解液中A20、TLR2、TLR4、pNFκB-p65及pp38MAPK水平。以上所有指标均与MRL/lpr小鼠未处理组、阴性对照组BALB/c雌性小鼠进行比较。结果随着Daphnetin处理组小鼠PBMC裂解液中A20蛋白水平显著升高(P 0.01),小鼠尿蛋白及血清BUN减少(P 0.001,P 0.001),其生存期(存活率)虽低于阴性对照健康鼠,但明显优于未处理组狼疮鼠(66.7%88.9%100%);血清中anti-dsDNA IgG、IL-6和TNF-α水平明显下降(P 0.01,P 0.01,P0.001);PBMC裂解液中TLR2、TLR4、pNFκB-p65、pp38MAPK水平均有明显下降(P_均0.05)。结论 PBMC中A20水平升高可抑制TLR2、4-p38MAPK/NF-κB信号通路,从而明显改善对MRL/lpr狼疮模型小鼠的炎症反应。     

皮肤科学基础

961894 BXSB小鼠肝肾脾脏器中C-myc和N-ras原癌基因的表达/周平…//中国皮肤性病学杂志。-1996,10(2).-72,93 用同位素标记CDNA探针的斑点杂交法观察了BXSB小鼠肝、肾、脾脏器中C-myc的N-ras原癌基因的表达情况,从分子水平上探讨SLE免疫功能紊乱的基因调控机制。研究结果表明SLE发病较重的4～6月龄BXSB雄鼠脾脏和肾脏均表达C-myc mRNA,肝     

桥粒芯糖蛋白1、3在HaCaT细胞、A431细胞及原代角质形成细胞中的表达

【摘要】 目的 测定不同类型角质形成细胞（KC）桥粒芯糖蛋白（DSG）1、DSG3及DSG1 mRNA、DSG3 mRNA表达。 方法 不同KC（HaCaT细胞、A431细胞及原代KC）培养后,直接免疫荧光观察细胞DSG1、DSG3的表达,定量聚合酶链反应（qPCR）测定DSG1 mRNA、DSG3 mRNA相对表达水平。 结果 DSG1与DSG3表达于三种角质形成细胞,荧光强度显示,A431细胞高于HaCaT细胞,HaCaT细胞高于原代KC。三种细胞均表达DSG1、DSG3 mRNA,原代KC DSG1与DSG3 mRNA的相对表达量分别为HaCaT细胞的291.7%及237.4%,差异有统计学意义（P < 0.01）;A431细胞DSG1 mRNA为HaCaT细胞的0.1%、DSG3 mRNA则为HaCaT细胞的18.8%,差异有统计学意义（P < 0.05）。 结论 三种KC均可用于对DSG1、DSG3的相关研究;相对而言,正常培养的A431细胞表面DSG1、DSG3表达较HaCaT细胞及原代KC高;原代KC DSG1、DSG3 mRNA水平较HaCaT细胞及A431细胞高。     

Unique therapeutic effects of the Japanese-Chinese herbal medicine, Sairei-to, on Th1/Th2 cytokines balance of the autoimmunity of MRL/lpr mice

Sairei-to, one of the Japanese-Chinese herbal medicines has been used for the treatment of various diseases, especially collagen disease and edema in nephrotic syndrome. However, the mechanism of the therapeutic effects remains uncertain. Therefore, we investigated the immunological changes of skin, kidney, spleen cells and serum in autoimmune-prone MRL/lpr, MRL/n and C57BL/6J mice treated with Sairei-to. In MRL/lpr mice treated with Sairei-to, the improvement of proteinuria, reduction in the number of hematoxylin bodies in kidney, and reduced serum levels of blood urea nitrogen were observed. These results indicate that Sairei-to can improve or inhibit the progression of lupus nephritis. The proportion of CD19 and the serum levels of IgG1, which is one of the pathogenesis of lupus dermatoses and lupus nephritis, were significantly reduced in Sairei-to-treated MRL/lpr mice. Therefore, it is suspected that the B cell function was suppressed by Sairei-to. In addition, CD4/8 ratio in spleen cells and the degree of lymphoproliferation in MRL/lpr mice also decreased. Interestingly, IL-4 producing spleen cells were increased significantly by ELISPOT assay, and IFN-gamma mRNA expressions were reduced in Sairei-to-treated MRL/lpr mice. Regarding the Th balance, an imbalance towards Th1 predominance may play a significant role in MRL/lpr mice, and the Th1 axis was suppressed and the Th2 axis became predominant in Sairei-to-treated MRL/lpr mice. On the other hand, Th2 cell type immunoglobulins (IgG1) were suppressed. These results suggested that Sairei-to is potential for impairing shifted Th1/Th2 balance and hypergammaglobulinemia resulting in therapeutic effects.     

系统性红斑狼疮患者T淋巴细胞CD70基因表达及其启动子区域甲基化状态的研究

目的 探讨系统性红斑狼疮（SLE）患者T淋巴细胞CD70mRNA和蛋白的表达及CD70基因启动子DNA甲基化的状态。方法 分离15例活动期SLE患者、15例非活动期SLE患者和15例健康对照外周血CD4+与CD8+细胞,用实时定量逆转录PCR（RT-PCR）方法检测CD4+和CD8+细胞CD70 mRNA转录水平,流式细胞仪检测CD4+CD70+ 细胞和CD8+CD70+细胞百分率,亚硫酸氢钠基因测序法检测CD4+细胞和CD8+细胞CD70基因启动子区域甲基化水平。组间比较采用单因素方差分析,组间两两比较采用SNK-q检验。 结果 ①活动期、非活动期SLE患者CD4+细胞CD70 mRNA转录水平分别为0.82 ± 0.12和0.73 ± 0.11,明显高于健康对照组（0.45 ± 0.09）,F = 53.017,P < 0.01,活动期SLE患者CD4+细胞的CD70 mRNA转录水平显著高于非活动期SLE患者（P < 0.05）。活动期、非活动期SLE患者外周血CD4+CD70+细胞百分率分别为80.30% ± 11.04% 和66.80% ± 3.98%,明显高于健康对照组（12.48% ± 3.45%）,F = 311.517,P < 0．01,活动期SLE患者CD4+CD70+细胞百分率显著高于非活动期SLE患者（P值 < 0.05）。SLE患者外周血CD70+CD4+细胞百分率与SLE疾病活动度呈显著正相关（r = 0.792,P = 0.000）。活动期、非活动期SLE患者组的CD4+细胞CD70基因启动子序列-600 ~ -300 bp 区域平均甲基化水平分别为0.32 ± 0.05和0.36 ± 0.05,明显低于健康对照组（0.62 ± 0.05）,F = 152.64,P < 0.01,活动期平均甲基化水平明显低于非活动期SLE患者组（P < 0.05）。结论 CD4+细胞CD70基因启动子区域处于低甲基化状态,这种低甲基化状态可能是CD70过度表达的直接原因。     

凋亡调控分子BclGL表达与系统性红斑狼疮患者外周血单一核细胞凋亡的研究

【摘要】 目的 探讨系统性红斑狼疮（SLE）患者外周血单一核细胞（PBMC）中凋亡调控分子BclGL的表达及其意义。 方法 流式细胞仪检测20例活动期SLE患者（A-SLE）、18例非活动期SLE患者（I-SLE）以及30例健康对照者PBMC的细胞绝对数;用膜联蛋白V-异硫氰酸荧光素/碘化丙啶（Annexin V-FITC/PI）细胞凋亡双染试剂盒检测各组PBMC早期凋亡率;荧光定量PCR技术检测各组PBMC中BclGL mRNA的表达量;Western 印迹检测BclGL蛋白表达量;酶联免疫吸附试验（ELISA）检测各组血清中干扰素（IFN）-α水平;采用SPSS13.0统计软件进行组间非参数Mann-Whitney或Kruskal-Wallis检验,并使用Pearson相关分析法分析SLE患者PBMC中BclGL表达量与细胞凋亡率及临床指标间的相关性。 结果 A-SLE患者外周血中PBMC细胞绝对数［（0.16 ± 0.06） × 109/L］低于I-SLE［（0.27 ± 0.14） × 109/L］及健康对照［（0.34 ± 0.23） × 109/L］（均P < 0.01）;A-SLE患者PBMC凋亡率（22.6% ± 1.1%）较I-SLE（16.4% ± 0.9%）及健康对照（10.1% ± 0.4%）升高,I-SLE患者也高于健康对照（均P < 0.01）;A-SLE患者PBMC中BclGL表达量高于I-SLE及健康对照（均P < 0.01）;SLE患者外周血血清IFN-α含量［（32.5 ± 2.2） μg/L］较健康对照［（15.5 ± 1.3） μg/L］增高（均P < 0.01）;SLE患者PBMC中上调的BclGL表达与PBMC凋亡率（r = 0.486,P < 0.01）及SLE疾病活动指数（SLEDAI）、抗核抗体（ANA）滴度、IFN-α水平呈正相关（r = 0.496,0.516,0.535,均P < 0.01）,与患者补体C3水平呈负相关（r = －0.515,P < 0.01）。结论 SLE患者PBMC中BclGL分子表达上调可能参与SLE患者PBMC的凋亡异常,从而在SLE发病中起作用。 【关键词】 红斑狼疮,系统性; 外周血单一核细胞; BclGL; 细胞凋亡     

Pathogenesis of lupus dermatoses in autoimmune mice. XIX. Attempts to induce subepidermal immunoglobulin deposition in MRL/Mp-+/+ mice

The deposition of immunoglobulin (Ig) at the dermo-epidermal junction (DEJ) of the skin, frequently observed in autoimmune mouse strains, is similar to that seen in patients with systemic lupus erythematosus (SLE). MRL/Mp-lpr/lpr (MRL/lpr) mice have an autosomal recessive mutant gene, lpr, which produces massive T-cell proliferation and accelerates the onset of autoimmune diseases. MRL/Mp-+/+ (MRL/n) mice lack the lpr gene, and do not develop autoimmune disease during the first year after birth under pathogen-free conditions. To verify the mechanisms of subepidermal Ig deposition in the skin of LE, we designed an experiment in which we could induce Ig deposition in the control MRL/n mice. Intraperitoneal injection of lymphoproliferative cells of aged MRL/lpr mice induced splenomegaly and splenic granulomatous angitis in the control MRL/n mice. Lipopolysaccharide (LPS), a polyclonal B-cell activator, induced slight splenomegaly and relatively high levels of serum Ig. Dermatopathological investigation revealed mild lymphocyte infiltration without positive Ig deposition at the DEJ of MRL/n mice treated with proliferative T cells. Injection of both proliferative T cells and LPS induced 50% positivity of subepidermal Ig deposition, and high levels of serum immunoglobulins and anti-double stranded DNA (anti-dsDNA) antibodies. These changes were not observed in MRL/n mice injected with thymocytes of newborn MRL/lpr mice. Skin lesions and lupus nephritis were not demonstrated in any of the mice tested. This study suggest that both the mild inflammatory reaction and the presence of anti-dsDNA antibodies are required for the induction Ig deposition at the DEJ in the skin of LE patients.     

Evaluation of the Japanese-Chinese Herbal Medicine,Kampo, for the Treatment of Lupus Dermatoses in Autoimmune Prone MRL/Mp-lpr/lpr Mice

Kampo, a Japanese-Chinese traditional herbal medicine, has been used for the treatment of various diseases for about 3,000 years in China. Among herbal medicines, Sairei-to is well known for improving the symptoms of rheumatoid arthritis (RA) and other collagen diseases. However, its immunosuppressive effects on autoimmune cutaneous phenomena are not completely understood. We investigated the effects of Sairei-to on the development of lupus dermatoses in autoimmune-prone MRL/Mp-lpr/lpr (MRL/lpr) mice, an animal model which spontaneously develops skin lesions similar to those seen in human lupus erythematosus. Virgin female MRL/lpr mice at 1 month of age, which were treated orally with Sairei-to, had reduced amounts of IgG deposition at the dermoepidermal junction, titers of anti-DNA antibodies and rheumatoid factor, and lymphoproliferation. These results support the use of traditional herbal medicines in patients with human RA and systemic lupus erythematosus.     

新疆80例恶性黑素瘤BRAF基因突变分析

目的 探讨BRAF基因突变与恶性黑素瘤临床表现的关系。方法 PCR及DNA直接测序法对新疆80例恶性黑素瘤及30例正常皮肤石蜡包埋组织BRAF基因11、15外显子进行检测。结果 80例恶性黑素瘤19例发生BRAF基因突变,突变率为23.8%（19/80）;有17例突变发生于15外显子,突变率为89.5% （17/19）,其中V600E突变占BRAF基因15外显子突变的88.2% （15/17）;2例突变位于11外显子,突变率10.5%（2/19）;30例正常皮肤组织均未发现BRAF基因突变。患者平均发病年龄为57.5岁,年龄在60岁以下患者BRAF基因突变率显著高于60岁以上（χ2 = 6.613,P < 0.05）。黏膜、肢端、非肢端突变率分别为：18.2%（4/21）,14.7%（5/34）,41.7%（10/24）,差异具有统计学意义（χ2 = 6.167,P < 0.05）。BRAF基因突变与恶性黑素瘤患者性别、民族、有无淋巴结转移无明显相关性（P > 0.05）。结论 BRAF基因仍为新疆地区恶性黑素瘤热点突变基因,且以该基因15外显子V600E突变为主。BRAF基因突变与恶性黑素瘤患者发病年龄、发病部位密切相关,而与民族、性别、有无淋巴结转移无相关性。     

套细胞淋巴瘤伴皮肤虫咬样反应一例

【摘要】 患者男,74岁,确诊套细胞淋巴瘤5年,躯干、四肢丘疱疹伴瘙痒10个月就诊。皮疹瘙痒剧烈,给予抗组胺药物对症治疗不能缓解。体检：躯干、四肢皮肤见散在绿豆至黄豆大小红色丘疹及丘疱疹,部分表面见浅表结痂,以双上肢皮损为主,颈部、双侧腹股沟可触及肿大淋巴结,约2 cm × 1 cm。颈部淋巴结病理示,正常淋巴结结构完全破坏,中等大淋巴样细胞呈结节状或弥漫增生浸润,免疫组化示CD20（+++）,CD79α（+++）, Bcl-2（++）,细胞周期蛋白D1（+++）,CD5（++弱）,CD43（++）,Bcl-6（++）, PAX-5（+++）,κ（+++）,λ（±） ,Ki-67（10% ~ 30%+不均）。皮损组织病理及免疫组化：表皮大致正常,真皮浅中层血管、附属器周围见以中等大小淋巴样细胞为主的团灶状浸润,其间散在嗜酸性粒细胞;免疫组化：CD3（部分+）,CD5（弥漫性+）,CD20（部分+）,细胞周期蛋白D1（部分+）,Ki-67（10% +）。根据临床资料、淋巴结及皮损组织病理及免疫组化,诊断为套细胞淋巴瘤伴皮肤虫咬样反应。     

Characterization of cutaneous infiltrates in MRL/lpr mice monitored from onset to the full development of lupus erythematosus-like skin lesions.

The skin is a primary site injured in lupus erythematosus (LE), but it is still controversial whether the injury is due to cells of the mononuclear infiltrate and which immunocompetent cells play the major role in the development of cutaneous LE. To better characterize the role of immunocompetent cells, we performed an immunohistochemical examination of these cells in LE-like skin lesions in MRL/Mp-lpr/lpr (MRL/lpr) mice. Skin lesions in 60 female MRL/lpr mice were monitored from onset to full development. Skin specimens from each stage were stained for epidermal Ia+ Langerhans cells (Ia(+)-LC), for Thy-1+ dendritic epidermal cells (Thy-1+DEC), and for the phenotype of the mononuclear cell infiltrates. The numbers of Ia(+)-LC and Thy-1+DEC were decreased markedly in the skin lesions at the later stage. However, the numbers of Ia(+)-LC were increased significantly in the central portion of lesions at an early stage and in the peripheral portion of lesions later. L3T4+ cells were predominant, and the L3T4/Lyt-2 ratio was high in dermal infiltrates at an early stage. With advancing stage, the L3T4/Lyt-2 ratio gradually decreased in dermal infiltrates, whereas the Thy-1.2/Lyt-2 ratio in lymph nodes was reversed. L3T4+ cells were especially predominant in dermal infiltrates under the epidermis with increased numbers of Ia(+)-LC. This immunohistochemical analysis of a mouse model of cutaneous LE revealed changes in immunocompetent cell populations with the evolution of skin lesions, and we conclude that Ia(+)-LC and Thy-1+DEC, as well as L3T4+ and Lyt-2+ cells, may play pathogenic roles in the development of skin lesions.