本文選題：紅斑狼瘡　切入點：系統(tǒng)性　出處：《安徽醫(yī)科大學》2017年碩士論文　論文類型：學位論文

【摘要】：目的:探討系統(tǒng)性紅斑狼瘡(systemic lupus erythematosus,SLE)組織原位記憶T細胞(tissue resident memory T cells,Trm cells)與SLE皮損的相關性,為研究SLE患者皮損的形成機制提供新思路,尋找狼瘡皮損治療的新靶點。方法:本研究連續(xù)性納入2015年7月至2016年4月于安徽省立醫(yī)院風濕免疫科門診或住院部初診的SLE患者20例(男性2例,女性18例),所有患者均符合1997年美國風濕病學會(American College of Rheumatology,ACR)制定的SLE分類標準。健康對照10例選自同期我院健康體檢中心體檢者(男性1例,女性9例),平均年齡(26.4±4.8)歲。皮膚對照組10例選自同期我院美容中心。所有研究對象均被告知并簽署知情同意書。收集SLE患者及健康對照外周血,分離PBMC后流式細胞術檢測SLE患者和健康對照外周血及T淋巴細胞亞群中CCR7-CD45RA-效應記憶T細胞(effector memory T cells,Tem cells)和CCR7-CD45RA+效應T細胞(effector T cells,Teff cells)亞群的比例變化;收集SLE患者皮損處皮膚組織及健康對照正常部位皮膚組織,免疫熒光法觀察SLE患者及健康對照真皮和表皮間Ig A、Ig G、Ig M、C3免疫復合物沉積情況;免疫組織化學法檢測SLE患者皮損處皮膚組織及健康對照正常部位皮膚組織中CD4、CD8以及Trm細胞的特征性表面標志CD103分子表達,比較CD103陽性細胞在SLE患者皮損組織和健康對照正常皮膚組織中的表達。結果:(1)與健康對照相比,SLE患者外周血中CD4+Tem、CD4+Teff、CD8+Tem、CD8+Teff細胞在外周血T淋巴細胞亞群中所占比例均明顯升高,差異有統(tǒng)計學意義(12.56±3.40 vs 8.19±2.53,p=0.004;2.54±1.52 vs 1.34±0.82,p=0.029;15.31±3.62 vs 7.05±2.99,p=0.000;13.11±5.38 vs 3.73±1.33,p=0.000);(2)與健康對照相比,SLE患者CD4+Tem、CD4+Teff、CD8+Tem、CD8+Teff細胞在外周血中的比例均明顯升高,差異有統(tǒng)計學意義(8.42±2.67 vs 5.81±1.97,p=0.011;1.55±0.96 vs 0.79±0.51,p=0.008;10.36±3.60 vs 5.27±2.39,p=0.000;8.16±4.10 vs 2.56±0.80,p=0.000);(3)皮膚組織免疫熒光染色熒光顯微鏡下觀察到在SLE患者皮損處表皮和真皮交界處有大量Ig A、Ig M、補體C3呈線型沉積,而健康對照者皮膚組織中沒有免疫復合物沉積;(4)皮膚組織病理與健康對照相比,SLE患者皮損處組織HE染色可見真皮層中浸潤淋巴細胞明顯增多。免疫組織化學染色顯示浸潤淋巴細胞中表達CD4、CD8、CD103分子的細胞數(shù)量均較健康對照有不同程度增多。結論:SLE患者體內(nèi)存在Tem細胞和Teff細胞的異常活化,其表達較健康對照明顯升高。Trm細胞局部浸潤導致SLE患者皮損部位皮膚組織表皮和真皮下免疫復合物沉積。Trm細胞浸潤可能與SLE患者皮損形成相關。
[Abstract]:Objective: To investigate the effects of systemic lupus erythematosus (systemic lupus, erythematosus, SLE) in situ memory T cells (tissue resident memory T cells, Trm cells) associated with SLE lesions, and provide new ideas for the study on the formation mechanism of the skin lesions of patients with SLE, to find a new target for the treatment of lupus lesions. Methods: This study included continuity from July 2015 to April 2016 in Anhui Provincial Hospital Department of rheumatology outpatient or inpatient department of newly diagnosed SLE patients 20 cases (2 cases, male 18 cases of female), all the patients were consistent with the 1997 American College of Rheumatology (American College of Rheumatology, ACR SLE) classification standard. 10 healthy subjects were selected from the same period in our hospital health examination center examination (male 1 cases, female 9 cases), average age (26.4 + 4.8) years old. The skin beauty center in our hospital 10 cases of control group were selected from the same period. All the subjects were informed and signed informed consent. Collect SL E patients and healthy control peripheral blood PBMC after separation by flow cytometry in patients with SLE and healthy control peripheral blood T lymphocyte subsets and CCR7-CD45RA- effect in memory T cells (effector memory T cells, Tem cells) and CCR7-CD45RA+ (effector T cells T cells, Teff cells) subsets proportion; collect SLE patients and healthy skin tissue and normal skin tissue site, immunofluorescence of SLE patients and healthy controls between the dermis and epidermis Ig A, Ig G, Ig M, C3 immune complex deposition; detection of skin tissue in normal position in CD4 lesions of patients with SLE and healthy skin tissue by immunohistochemical method CD8, Trm and cell surface markers characteristic of the expression of CD103, CD103 positive cells were expressed in normal skin tissues in the lesions of patients with SLE and healthy. Results: (1) and health controls, SLE patients The peripheral blood CD4+Tem, CD4+Teff, CD8+Tem, CD8+Teff cells were significantly increased in the proportion of peripheral blood T lymphocyte subsets in proportion, the difference was statistically significant (12.56 + 3.40 vs 8.19 + 2.53, p=0.004; 2.54 + 1.52 vs 1.34 + 0.82, p=0.029; 15.31 + 3.62 vs 7.05 + 2.99, P =0.000 13.11 + 5.38; 3.73 + 1.33 vs, p=0.000); (2) compared with healthy controls, CD4+Tem patients, SLE CD4+Teff, CD8+Tem, the proportion of CD8+Teff cells in peripheral blood were significantly increased, the difference was statistically significant (8.42 + 2.67 vs 5.81 + 1.97, p=0.011; 1.55 + 0.96 vs 0.79 + 0.51. P=0.008; 10.36 + 3.60 vs 5.27 + 2.39, p=0.000; 8.16 + 4.10 vs 2.56 + 0.80, p=0.000); (3) skin tissue immunofluorescence staining under fluorescence microscope observed a large number of Ig A, at the junction of the skin lesions of patients with SLE Ig M in the epidermis and dermis, complement C3 linear deposition, and healthy control skin tissue without immune complex Deposit; (4) compared with healthy skin tissue pathological lesions of patients with SLE, tissue HE staining in the dermis infiltrating lymphocytes increased significantly. Immunohistochemical staining showed that the expression of CD4, CD8 lymphocytes, cell number of CD103 molecules were compared with healthy controls with different degree increased. Conclusion: the aberrant activation of Tem cells and Teff cells of SLE patients compared with healthy controls, the expression of.Trm was significantly higher in patients with SLE cell infiltration in infiltrating lesions of skin tissue under the epidermis and dermal immune complex deposition of.Trm cells may be associated with lesions of patients with SLE.

【學位授予單位】：安徽醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R593.241

【參考文獻】

相關期刊論文 前1條

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