發(fā)布時(shí)間：2018-06-12 11:46

  本文選題：梅毒螺旋體 + 神經(jīng)梅毒��； 參考：《安徽醫(yī)科大學(xué)》2017年博士論文

【摘要】：第一部分 CXCL13/CXCR5在神經(jīng)梅毒中樞神經(jīng)系統(tǒng)中對(duì)B細(xì)胞的招募作用研究背景:梅毒是由梅毒螺旋體感染引起的一種性傳播疾病,神經(jīng)梅毒可以發(fā)生在梅毒螺旋體感染機(jī)體后的始終。越來越多的證據(jù)表明免疫應(yīng)答參與了神經(jīng)梅毒中樞神經(jīng)損傷,其中體液免疫發(fā)揮了重要的作用。而迄今為止神經(jīng)梅毒患者中樞神經(jīng)系統(tǒng)中體液免疫的啟動(dòng)和維持機(jī)制尚不明確。研究方法:使用流式細(xì)胞術(shù)分析111個(gè)梅毒患者腦脊液樣本中的B細(xì)胞及B細(xì)胞亞群的分布情況。樣本包括23個(gè)無癥狀神經(jīng)梅毒、43個(gè)有癥狀神經(jīng)梅毒和45個(gè)非神經(jīng)梅毒,其中分別有36個(gè)和17個(gè)隨訪病人符合隨訪要求。使用ELISA法檢測(cè)腦脊液中免疫球蛋白(IgM,IgA和IgG)、CXCL13的濃度。使用改良后的24孔小室進(jìn)行趨化實(shí)驗(yàn)和中和實(shí)驗(yàn),分析不同組別梅毒患者的腦脊液對(duì)B細(xì)胞的趨化作用;CXCL13中和抗體抑制神經(jīng)梅毒患者腦脊液樣本中的CXCL13后,分析趨化后B細(xì)胞比例和B細(xì)胞亞群的變化情況。使用免疫組化法檢測(cè)鞘內(nèi)梅毒瘤病變組織的中spirochete、CXCR5、CD20+B細(xì)胞、CD3+T細(xì)胞、CD138+漿細(xì)胞,和CD35+濾泡狀樹突狀細(xì)胞及其分泌的趨化因子CXCL13的表達(dá)情況。研究結(jié)果:我們發(fā)現(xiàn):相較于非神經(jīng)梅毒,神經(jīng)梅毒患者腦脊液中B細(xì)胞的比例顯著升高(P0.001),并且B細(xì)胞處于激活狀態(tài)。在未治療的神經(jīng)梅毒患者免疫球蛋白指數(shù)(IgM,IgA和IgG指數(shù))顯著高于非神經(jīng)梅毒,并且與疾病的進(jìn)展有相關(guān)性。神經(jīng)梅毒患者腦脊液中的CXCL13的表達(dá)水平顯著升高(P0.001)。此外,腦脊液中高水平的CXCL13可以在體內(nèi)和體外介導(dǎo)B細(xì)胞向中樞的遷移。更重要的是,神經(jīng)梅毒患者腦脊液中的B細(xì)胞、免疫球蛋白指數(shù)以及CXCL13的水平三者之間均呈顯著的正相關(guān)(P值均0.05)。最后,神經(jīng)梅毒患者腦脊液對(duì)于B細(xì)胞的趨化指數(shù)顯著高于非神經(jīng)梅毒;腦脊液預(yù)先使用CXCL13中和抗體孵育后,可以阻止其對(duì)B細(xì)胞的趨化作用。腦實(shí)質(zhì)梅毒瘤病變組織中含有濾泡樣結(jié)構(gòu),其包含大量的B細(xì)胞、T細(xì)胞和漿細(xì)胞,以及在淋巴細(xì)胞間網(wǎng)狀排列的濾泡狀樹突狀細(xì)胞,并且表達(dá)CXCL13。研究結(jié)論:神經(jīng)梅毒患者中樞神經(jīng)系統(tǒng)中CXCL13/CXCR5可以介導(dǎo)外周血B細(xì)胞的聚集,通過形成異位生發(fā)中心促進(jìn)體液免疫應(yīng)答。這些結(jié)果為闡明神經(jīng)梅毒的中樞神經(jīng)損傷機(jī)制以及免疫治療提供了新的線索。第二部分 Th1/Th2相關(guān)細(xì)胞因子對(duì)IgG亞類在神經(jīng)梅毒患者腦脊液中分布的調(diào)控研究研究背景:神經(jīng)梅毒中樞神經(jīng)系統(tǒng)中存在激活的體液免疫應(yīng)答,在局部產(chǎn)生大量的免疫球蛋白,不僅有利于梅毒螺旋體在局部的清除作用,同時(shí)也可能參與中樞神經(jīng)系統(tǒng)的損傷作用。由于免疫球蛋白的產(chǎn)生以及抗體型別和類別轉(zhuǎn)換依賴細(xì)胞因子的微環(huán)境,而IgG不同的亞類的功能也有所不同,所以我們檢測(cè)神經(jīng)梅毒患者腦脊液中IgG亞類的分布情況以及細(xì)胞因子對(duì)其的調(diào)控作用。研究方法:采用超敏多因子電化學(xué)發(fā)光技術(shù)檢測(cè)126例腦脊液樣本中的固有免疫細(xì)胞因子(IL-1β,IL-6,IL-8,TNF-α),Th1細(xì)胞相關(guān)的細(xì)胞因子(IFN-γ,IL-2,IL-12p70)和Th2細(xì)胞相關(guān)的細(xì)胞因子(IL-4,IL-10,IL-13);這126例樣本包括15個(gè)正常對(duì)照,無癥狀神經(jīng)梅毒23例,有癥狀神經(jīng)梅毒43例,非神經(jīng)梅毒45例。其中符合第一次隨訪和第二次隨訪要求的神經(jīng)梅毒病人各有31例和15例。使用ELISA法檢測(cè)腦脊液樣本中IgG1,IgG2,IgG3和IgG4的濃度。研究結(jié)果:我們發(fā)現(xiàn)相較于非神經(jīng)梅毒和正常對(duì)照組,神經(jīng)梅毒患者腦脊液中的固有免疫細(xì)胞因子(IL-1β,IL-6,IL-8,TNF-α),Th1細(xì)胞相關(guān)的細(xì)胞因子(IFN-γ,IL-2,IL-12p70)和Th2細(xì)胞相關(guān)的細(xì)胞因子(IL-4,IL-10,IL-13)均顯著高于正常對(duì)照(P0.05)和非神經(jīng)梅毒(P0.05)。神經(jīng)梅毒患者腦脊液中IgG1,IgG2,IgG3和IgG4的濃度顯著高于非神經(jīng)梅毒(P0.05)和正常對(duì)照組(P0.001),然而非神經(jīng)梅毒和正常對(duì)照組之間IgG1,IgG2,IgG3和IgG4的濃度無顯著差異。神經(jīng)梅毒患者中樞神經(jīng)系統(tǒng)中Th1和Th2呈現(xiàn)協(xié)同共存作用,分別分泌IFN-γ和IL-13,并且這兩種細(xì)胞因子與免疫球蛋白亞類(IgG1,IgG2,IgG3,IgG4)呈正相關(guān),特別是IgG1和IgG3。在隨訪中發(fā)現(xiàn),神經(jīng)梅毒患者腦脊液中IgG1,IgG2和IgG3在第一次治療后(P0.05)顯著下降,然而在第二次隨訪中IgG3的水平較治療前無顯著差異(P=0.147)。研究結(jié)論:神經(jīng)梅毒患者腦脊液中的IFN-γ和IL-13參與腦脊液中IgG亞類的調(diào)控,主要是IgG1和IgG3的類別轉(zhuǎn)換;IgG3,作為一個(gè)保護(hù)性免疫球蛋白,可能可以作為評(píng)估神經(jīng)梅毒患者臨床治療效果評(píng)判指標(biāo)。
[Abstract]:The first part of the study on the role of CXCL13/CXCR5 in the recruitment of B cells in the central nervous system of neurosyphilis: syphilis is a sexually transmitted disease caused by Treponema pallidum infection. Neurosyphilis can occur after the infection of the body of Treponema pallidum. More and more evidence suggests that the immune response is involved in the neurosyphilis central God. After injury, humoral immunity plays an important role. And to date, the mechanism of starting and maintaining humoral immunity in the central nervous system of neurosyphilis is not clear. Methods of flow cytometry were used to analyze the distribution of B cells and B subsets in the cerebrospinal fluid samples of 111 syphilis patients. The samples included 23 asymptomatic samples. Neurosyphilis, 43 symptomatic neurosyphilis and 45 non neurosyphilis, of which 36 and 17 patients were followed up for follow-up. The ELISA assay was used to detect the concentration of immunoglobulin (IgM, IgA and IgG) and CXCL13 in the cerebrospinal fluid. The modified 24 pore chamber was used for chemotaxis experiment and neutralization test to analyze different groups of syphilis patients. The chemotactic effect of cerebrospinal fluid on B cells; CXCL13 neutralization antibody inhibited CXCL13 in cerebrospinal fluid samples of patients with neurosyphilis, analyzed the proportion of B cells after chemotaxis and the changes of B cell subsets. Immunohistochemistry was used to detect spirochete, CXCR5, CD20+B cells, CD3+T cells, CD138+ plasma cells, and CD35+ in the tissue of intrathecal syphilitic lesions. The expression of follicular dendritic cells and their secreted chemokine CXCL13. Results: we found that compared to non neurosyphilis, the proportion of B cells in the cerebrospinal fluid of patients with neurosyphilis increased significantly (P0.001), and the B cells were in the active state. The immunoglobulin index (IgM, IgA and IgG index) in patients with untreated syphilis of the syphilis (IgM, IgA and IgG) It is significantly higher than non neurosyphilis and is associated with the progression of the disease. The level of CXCL13 expression in the cerebrospinal fluid of patients with neurosyphilis increased significantly (P0.001). In addition, the high level of CXCL13 in cerebrospinal fluid can mediate the migration of B cells to the center in vivo and in vitro. More importantly, the B cells in the cerebrospinal fluid of the neurosyphilis patients, the immune ball. There was a significant positive correlation between the protein index and the level of the level of CXCL13 (P value is 0.05). Finally, the chemotactic index of cerebrospinal fluid to B cells in patients with neurosyphilis was significantly higher than that of non neurosyphilis; cerebrospinal fluid was incubated with CXCL13 neutralization antibody in advance, which could prevent the chemotaxis of B cells from the B cells. A follicular structure contains a large number of B cells, T cells and plasma cells, as well as follicular dendritic cells in the reticular arrangement of lymphocytes, and the expression of CXCL13. studies: CXCL13/CXCR5 can mediate the aggregation of peripheral blood B cells in the central nervous system of neurosyphilis patients and promote humoral immunity through the formation of ectopic germinal center. These results provide new clues to elucidate the mechanism of neurosyphilis's central nervous injury and immunotherapy. Second the study of the regulation of the distribution of the IgG subclass in the cerebrospinal fluid of patients with neurosyphilis by Th1/Th2 related cytokines: the activation of the humoral immune response in the neurosyphilis central nervous system, in the Bureau The ministry produces a large number of immunoglobulin, which is not only conducive to the local scavenging of Treponema pallidum, but also may be involved in the damage of the central nervous system. Because of the production of immunoglobulin and the conversion of antibody type and category to the microenvironment of cell factors, the function of the subclass of IgG is different, so we examine the function of the subclass. The distribution of IgG subclass in cerebrospinal fluid of patients with neurosyphilis and the regulation of cytokines in the cerebrospinal fluid. Methods: using hypersensitivity multifactor electrochemiluminescence technique to detect the innate immune cell factors (IL-1 beta, IL-6, IL-8, TNF- alpha) in 126 samples of cerebrospinal fluid and Th1 fine cell related cytokines (IFN- gamma, IL-2, IL-12p70) and Th2 cells Related cytokines (IL-4, IL-10, IL-13); these 126 samples included 15 normal controls, 23 asymptomatic neurosyphilis, 43 symptomatic neurosyphilis, and 45 non neurosyphilis, of which 31 and 15 of the patients met the first and second follow-up requirements of neurosyphilis. IgG1, IgG2, IgG3 in cerebrospinal fluid samples were detected by ELISA. And IgG4 concentration. Results: we found that the innate immune cell factors (IL-1 beta, IL-6, IL-8, TNF- alpha) in cerebrospinal fluid of patients with neurosyphilis compared to non neurosyphilis and normal control group, and Th1 cell related cytokines (IFN- gamma, IL-2, IL-12p70) and Th2 cell related cytokines (IL-4, IL-10,) were significantly higher than those of normal controls. P0.05) and non neurosyphilis (P0.05). The concentration of IgG1, IgG2, IgG3 and IgG4 in the cerebrospinal fluid of patients with neurosyphilis was significantly higher than that of non neurosyphilis (P0.05) and normal control group (P0.001). However, there was no significant difference in the concentration of IgG1, IgG2, IgG3 and IgG4 between the non neurosyphilis and the normal control group. IFN- gamma and IL-13 were secreted by CO coexistence, and the two cytokines were positively correlated with the subclass of immunoglobulin (IgG1, IgG2, IgG3, IgG4), especially in IgG1 and IgG3. in follow-up. The IgG1, IgG2, and IgG3 in the cerebrospinal fluid of patients with neurosyphilis decreased significantly after the first treatment (P0.05), however, at the second follow up levels No significant difference before treatment (P=0.147). Conclusions: IFN- gamma and IL-13 in cerebrospinal fluid of patients with neurosyphilis participate in the regulation of IgG subclass in cerebrospinal fluid, mainly the category conversion of IgG1 and IgG3; IgG3, as a protective immunoglobulin, may be used as a marker for evaluating the clinical therapeutic effect of patients with syphilis.
【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類號(hào)】：R759.13

【相似文獻(xiàn)】

相關(guān)期刊論文 前10條

1 周冼苡,張進(jìn)華,劉玉梅;以癲癇為首發(fā)癥狀的二期神經(jīng)梅毒誤診分析[J];中國皮膚性病學(xué)雜志;2001年05期

2 朱雀,朱旦,冒淑娟;神經(jīng)梅毒2例誤診分析[J];重慶醫(yī)學(xué);2003年11期

3 李子純;神經(jīng)梅毒2例[J];嶺南皮膚性病科雜志;2003年01期

4 周暉;神經(jīng)梅毒[J];嶺南皮膚性病科雜志;2003年03期

5 阮少川,石鑄,劉衛(wèi)彬,梁秀齡;神經(jīng)梅毒誤診分析[J];中國誤診學(xué)雜志;2003年01期

6 楊剛,繆體宗,唐文淵;神經(jīng)梅毒1例報(bào)道及文獻(xiàn)復(fù)習(xí)[J];重慶醫(yī)學(xué);2003年12期

7 謝江文,趙菊芳,顏政;神經(jīng)梅毒誤診1例[J];臨床薈萃;2004年06期

8 王煥玲,李世泰,盛瑞媛,郭濤,張振馨;神經(jīng)梅毒一例[J];中華皮膚科雜志;2004年05期

9 詹奕紅,魯叢霞;神經(jīng)梅毒8例臨床分析[J];臨床神經(jīng)病學(xué)雜志;2004年03期

10 黎志剛,曾仁山,吳江;以癲癇為首發(fā)癥狀的神經(jīng)梅毒1例[J];嶺南皮膚性病科雜志;2004年03期

相關(guān)會(huì)議論文 前10條

1 姚慶陽;;神經(jīng)梅毒10例分析[A];中華醫(yī)學(xué)會(huì)第十三次全國神經(jīng)病學(xué)學(xué)術(shù)會(huì)議論文匯編[C];2010年

2 涂江龍;吳偉;熊友生;艾陸軍;;神經(jīng)梅毒(附3例報(bào)道)[A];江西省中西醫(yī)結(jié)合學(xué)會(huì)第二次神經(jīng)科學(xué)術(shù)交流會(huì)論文匯編[C];2005年

3 蒙秉新;;我國神經(jīng)梅毒發(fā)病情況分析[A];中華醫(yī)學(xué)會(huì)第十二次全國皮膚性病學(xué)術(shù)會(huì)議論文集[C];2006年

4 石強(qiáng);黃旭升;黃德暉;于生元;管維平;吳衛(wèi)平;蒲傳強(qiáng);;神經(jīng)梅毒的臨床特征與診斷——附3例報(bào)告并文獻(xiàn)復(fù)習(xí)[A];第九次全國神經(jīng)病學(xué)學(xué)術(shù)大會(huì)論文匯編[C];2006年

5 馮永芳;陳春梅;孔慶云;張開;劉雯;;神經(jīng)梅毒誤診一例[A];2008全國中西醫(yī)結(jié)合皮膚性病學(xué)術(shù)會(huì)議論文匯編[C];2008年

6 譚燕;方雅秀;施海姍;鄭東;;80例神經(jīng)梅毒的臨床特征和預(yù)后研究[A];第十一屆全國神經(jīng)病學(xué)學(xué)術(shù)會(huì)議論文匯編[C];2008年

7 張宇;;神經(jīng)梅毒9例臨床分析[A];2009全國中西醫(yī)結(jié)合皮膚性病學(xué)術(shù)會(huì)議論文匯編[C];2009年

8 蔣法興;胡白;湯其強(qiáng);趙政龍;吳愛麗;張思平;廖理超;劉金麗;周海林;王千秋;;18例神經(jīng)梅毒患者回顧性分析[A];2009全國中西醫(yī)結(jié)合皮膚性病學(xué)術(shù)會(huì)議論文匯編[C];2009年

9 徐曼丹;韋巧靈;黃宇;雷麗華;;神經(jīng)梅毒患者的護(hù)理體會(huì)[A];第三屆重癥醫(yī)學(xué)大會(huì)論文匯編[C];2009年

10 漆學(xué)良;涂江龍;黃衛(wèi);盧潔;熊友生;鄧麗影;;以關(guān)節(jié)炎為首發(fā)癥狀的神經(jīng)梅毒[A];中華醫(yī)學(xué)會(huì)第十三次全國神經(jīng)病學(xué)學(xué)術(shù)會(huì)議論文匯編[C];2010年

相關(guān)重要報(bào)紙文章 前1條

1 劉y，

本文編號(hào)：2009560