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供体来源的CD19靶向T细胞输注 1

微小残留病 1

急性B淋巴细胞白血病 1

造血干细胞移植 1

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Advances in immunopathogenesis of adult immune thrombocytopenia

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《医学前沿（英文）》 2013年第7卷第4期页码 418-424 doi: 10.1007/s11684-013-0297-8

摘要：

Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by immune-mediated accelerated platelet destruction and/or suppressed platelet production. Although the development of autoantibodies against platelet glycoproteins remains central in the pathophysiology of ITP, several abnormalities involving the cellular mechanisms of immune modulation have been identified, and the pathways behind the immune-mediated destruction of platelets have opened new avenues for the design of specific immunotherapies in an attempt to reduce the platelet destruction. This review is primarily focused on the recent literature with respect to immunopathological mechanisms in patients with ITP.

关键词： primary immune thrombocytopenia B lymphocytes T lymphocytes antigen-presenting cells cytokines

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A rare case of B-lymphoproliferative disorder with villous lymphocytes harboring t(8;14)(q24;q32) translocation

null

《医学前沿（英文）》 2018年第12卷第3期页码 324-329 doi: 10.1007/s11684-017-0558-z

摘要：

Splenic lymphoma with villous lymphocytes (SLVL) or splenic marginal zone lymphoma with circulating villous lymphocytes is rare, and prolymphocytic transformation of SLVL is rarer. At present, only one case of SLVL with t(8;14)(q24;q32) translocation has been reported. In this study, we report a case of B-lymphoproliferative disorder with villous lymphocytes harboring t(8;14)(q24;q32) chromosome translocation that we inclined to SLVL with a prolymphocytic transformation. A 73-year-old female showed marked hepatosplenomegaly and high lymphocytosis (lymphocytes>200×10⁹/L). The abnormal lymphocytes had short coarse villi and round nuclei with prominent nucleoli. The immunophenotypes showed CD19⁺, CD20⁺, HLA-DR⁺, CD22⁺, CD5⁺, Kappa⁺, CD25^dim, CD71^dim, Lambda⁻, CD7⁻, CD10⁻, CD23⁻, CD34⁻, CD33⁻, CD13⁻, CD14⁻, CD117⁻, CD64⁻, CD103⁻, and CD11c⁻. The karyotype showed complex abnormality: 46XX,+3,−10, t(8;14)(q24;q32)[11]/46XX[⁹]. The cytoplasmic projection, immunological characteristics, and trisomy 3 chromosome abnormality supported the diagnosis of SLVL. However, the presence of prominent nucleoli and high lymphocytosis suggested prolymphocytic transformation, probably as a result of t(8,14) chromosome translocation. In this report, we described an unusual case of B-lymphoproliferative disorder with villous lymphocytes harboring t(8;14)(q24;q32) translocation, which could provide help in the diagnosis and differential diagnosis of B-lymphocytic proliferative diseases.

关键词： splenic lymphoma with villous lymphocytes splenic marginal zone lymphoma transformation chromosome translocation

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Tim-3 mRNA expression in peripheral blood lymphocytes from asthmatic patients

Xiaoxia LU, Weikun HU, Shengdao XIONG, Guopeng XU, Fen LAN

《医学前沿（英文）》 2009年第3卷第2期页码 187-190 doi: 10.1007/s11684-009-0033-6

摘要： The study aimed to detect the expression of the Th1-specific cell surface protein T cell Ig and mucin domain-containing molecule-3 (Tim-3) mRNA in peripheral blood lymphocytes isolated from asthmatic patients and to examine the correlation among Tim-3 mRNA, interleukin-4 (IL-4), interferon-γ (IFN-γ) level, and FEV1/FVC (force expiratory volume in one second/forced vital capacity) to explore the role of Tim-3 in the development and progression of asthmatic inflammation. Tim-3 mRNA expression was detected by reverse transcription polymerase chain reaction (RT-PCR). The IL-4 and IFN-γ levels were determined by using enzyme-linked immunosorbent assay (ELISA). The correlation among Tim-3 mRNA, IL-4, IFN-γ level, and pulmonary ventilatory capacity was analyzed. The expression of Tim-3 mRNA in patients with acute asthma exacerbation was 0.39±0.06, significantly higher than that in patients at the remission stage and controls (0.18±0.05 and 0.07±0.03, <0.05). The level of IL-4 in patients with acute asthma exacerbation was 68.42±10.54, significantly higher than that in the patients at the remission stage and controls (41.83±9.37 and 32.75±8.16, <0.05). The level of IL-4 in patients in remission was significantly higher than that in controls ( <0.05). The level of IFN-γ in patients with acute asthma exacerbation was 65.74±7.85, significantly lower than that in patients in remission and the control group (120.84±11.62 and 139.65±13.47, <0.05). The level of IFN-γ in patients in asthma remission was significantly lower than that in controls ( <0.05). Tim-3 mRNA expression was positively correlated with the level of IL-4 ( =0.68, <0.05) and negatively with the level of IFN-γ and pulmonary ventilatory capacity ( =-0.85, =-0.76, both <0.01). The increased expression of Tim-3 mRNA in peripheral blood lymphocytes might be involved in the development and progression of asthmatic inflammation.

关键词： asthma airway inflammation peripheral blood lymphocyte Tim-3

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Zfyve16 regulates the proliferation of B-lymphoid cells

Xuemei Zhao, Donghe Li, Qingsong Qiu, Bo Jiao, Ruihong Zhang, Ping Liu, Ruibao Ren

《医学前沿（英文）》 2018年第12卷第5期页码 559-565 doi: 10.1007/s11684-017-0562-3

摘要：

Zfyve16 (a.k.a. endofin or endosome-associated FYVE-domain protein), a member of the FYVE-domain protein family, is involved in endosomal trafficking and in TGF-β, BMP, and EGFR signaling. The FYVE protein SARA regulates the TGF-β signaling pathway by recruiting Smad2/3 and accelerating their phosphorylation, thereby altering their susceptibility to TGF-β-mediated T cell suppression. Zfyve16 binds to Smad4 and their binding affects the formation of Smad2/3-Smad4 complex in TGF-β signaling. However, the in vivo function of Zfyve16 remains unknown. In this study, we generated a Zfyve16 knockout mouse strain (Zfyve16^KO) and examined its hematopoietic phenotypes and hematopoietic reconstruction ability. The proportion of T cells in the peripheral blood of Zfyve16^KO mice increases compared with that in wild-type mice. This finding is consistent with the role of Zfyve16 in facilitating TGF-β signaling. Unpredictably, B cell proliferation is inhibited in Zfyve16^KO mice. The proliferation potential of Zfyve16^KO B-lymphoid cells also significantly decreases in vitro. These results suggest that Zfyve16 inhibits the proliferation of T cells, possibly through the TGF-β signaling, but upregulates the proliferation of B-lymphoid cells.

关键词： Zfyve16 endofin hematopoiesis TGF-β lymphocytes

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供体来源的CD19靶向T细胞输注可以消除异基因造血干细胞移植后对供者淋巴细胞无反应的急性B淋巴细胞白血病微小残留病 Article

程翼飞, 陈育红, 闫晨华, 王昱, 赵翔宇, 陈瑶, 韩伟, 许兰平, 张晓辉, 刘开彦, 王莎莎, 张隆基, 肖磊, 黄晓军

《工程（英文）》 2019年第5卷第1期页码 150-155 doi: 10.1016/j.eng.2018.12.006

摘要：

白血病复发仍是异基因造血干细胞移植（allogeneic hematopoietic stem cell transplantation，allo-HSCT）后急性B 淋巴细胞白血病（B cell acute lymphoblastic leukemia，B-ALL）治疗失败的主要原因。allo-HSCT 后B-ALL 复发患者的中位生存期很短。微小残留病（minimal residual disease，MRD）预示着造血干细胞移植（HSCT）后白血病将复发；消除MRD 将有效防止复发。HSCT 后治疗伴有MRD 的B-ALL 的主要方法是供者淋巴细胞输注（donor lymphoblastic infusion，DLI）。然而，在出现MRD 的患者中，约三分之一的患者对DLI 并无反应，且预后恶劣。虽然供体来源的CD19 导向嵌合抗原受体（chimeric antigen receptor-modified，CAR）修饰T 细胞（CART19）可能治愈白血病，但输注此类细胞的效率与安全性尚未在经过HSCT 后出现MRD 的B-ALL 患者当中进行过考察。在2014 年9 月至2018 年2 月期间，6 名患者均一次或多次输注了HSCT 供者提供的CD19 导向CAR 修饰T 细胞。其中有5 名患者（83.33%）的MRD 阴性得到缓解，而另1 名患者对CAR T 细胞并无反应。6 名患者中有3 名至今存活，白血病也并未复发。无患者出现急性移植物抗宿主病（acute graft-versus-host disease，aGVHD），也无患者死于细胞因子释放综合征。对于在allo-HSCT 后出现MRD 的B-ALL 患者且对DLI 并无反应的患者而言，供体来源的CAR T 细胞输注似乎是一种有效而安全的干预手段。

关键词：供体来源的CD19靶向T细胞输注造血干细胞移植急性B淋巴细胞白血病微小残留病