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【Blood】CCR5变异基因的骨髓移植治疗艾滋病证实
http://bloodjournal.hematologylibrary.org/cgi/content/abstract/blood-2010-09-309591v1
HIV entry into CD4+ cells requires interaction with a cellular receptor, generally either CCR5 or CXCR4. We have previously reported the case of an HIV-infected patient in whom viral replication remained absent despite discontinuation of antiretroviral therapy after transplantation with CCR5{Delta}32/{Delta}32 stem cells. However, it was expected that the long-lived viral reservoir would lead to HIV rebound and disease progression during the process of immune reconstitution. In the present study, we demonstrate successful reconstitution of CD4+ T cells at the systemic level as well as in the gut mucosal immune system following CCR5{Delta}32/{Delta}32 stem cell transplantation, while the patient remains without any sign of HIV infection. This was observed although recovered CD4+ T cells contain a high proportion of activated memory CD4+ T cells, i.e. the preferential targets of HIV, and are susceptible to productive infection with CXCR4-tropic HIV. Furthermore, during the process of immune reconstitution, we found evidence for the replacement of long-lived host tissue cells with donor-derived cells indicating that the size of the viral reservoir has been reduced over time. In conclusion, our results strongly suggest that cure of HIV has been achieved in this patient.
全文
http://bloodjournal.hematologylibrary.org/cgi/reprint/blood-2010-09-309591v1
相关阅读
Stem Cell Transplant Cures HIV In 'Berlin Patient'
http://www.huffingtonpost.com/2010/12/14/hiv-cure-berlin-patient_n_796521.html
Evidence for the cure of HIV infection by CCR5{Delta}32/{Delta}32 stem cell transplantation
http://bloodjournal.hematologylibrary.org/cgi/content/abstract/blood-2010-09-309591v1
Pubmed
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Link&db=pubmed&dbFrom=PubMed&from_uid=21148083
该案例中患者直肠粘膜的CD表面抗原的辅助受体和趋化因子表达
Expression of CD Surface Antigen and Chemokine Coreceptor in the Patient's Rectal Mucosa.
Mucosal cells isolated from rectal-biopsy specimens obtained 159 days after stem-cell transplantation were activated by phytohemagglutinin and analyzed with the use of flow cytometry. Cells were gated for lymphocytes by their characteristic forward- and side-scatter profile and were analyzed for CCR5 expression within the CD4+ T-cell population (Panel A). Macrophages were identified as CD11c+ and CD163+ within the CD4+ cell gate and analyzed for CCR5 expression (Panel . Whereas intestinal CD4+ T lymphocytes were negative (0.0%) for CCR5 expression, 14.6% of macrophages expressed CCR5 after engraftment, indicating a complete exchange of intestinal CD3+/CD4+ lymphocytes but not of intestinal CD3+/CD4+ macrophages.
screen.width-333)this.width=screen.width-333" width=640 height=496 title="Click to view full 2.JPG (863 X 669)" border=0 align=absmiddle> 这名患者在感染艾滋病病毒的同时患有白血病，于2007年接受骨髓移植，而捐献者体内的一种基因变异对艾滋病病毒有了天然的免疫力。
德国柏林沙丽泰医院的托马斯 施奈德及其同事表示，接受移植首都手术近4年后，这名患者摆脱了艾滋病病毒，体内任何地方似乎都不存在病毒的踪迹了。
骨髓移植是治疗诸如白血病之类绝症的最后手段。治疗要求首先破坏病人自身的骨髓—这本身就是极其痛苦的过程—然后从血型和免疫系统类型都基本一致的捐献者那里移植骨髓。数月后恢复期也是必要的。这样移植物才有能力生长并复原患者的免疫系统。
捐献者体内的基因变异会对一个名叫CCR5的受体造成影响。这种相当于细胞表面的门户，艾滋病病毒需要利用这一门户进入被感染的细胞。自上世纪90年代以来，科学家了解到某些人群—以北欧人为主—体内携带有这种变异，因而极少感染艾滋病病毒。
有研究者正致力于基因疗法，希望能治疗或治愈艾滋病，但这一技术目前尚处于试验阶段。
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作者:admin@医学,生命科学 2011-02-15 12:40
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