Strategies to accelerate immune recovery after allogeneic hematopoietic stem cell transplantation

The interplay existing between immune reconstitution and patient outcome has been extensively demonstrated in allogeneic hematopoietic stem cell transplantation. One of the leading causes of infection-related mortality is the slow recovery of T-cell immunity due to the conditioning regimen and/or age-related thymus damage, poor naïve T-cell output, and restricted T-cell receptor (TCR) repertoires. With the aim of improving posttransplantation immune reconstitution, several immunotherapy approaches have been explored. Donor leukocyte infusions are widely used to accelerate immune recovery, but they carry the risk of provoking graft-versus-host disease. This review will focus on sophisticated strategies of thymus function-recovery, adoptive infusion of donor-derived, allodepleted T cells, T-cell lines/clones specific for life-threatening pathogens, regulatory T cells, and of T cells transduced with suicide genes.     

T细胞核仁组成区嗜银蛋白对老年人肿瘤诊断的价值

目的　探讨老年肿瘤患者外周血T淋巴细胞核仁组成区嗜银蛋白的变化 ,及其与机体免疫关系。　方法　利用KL型肿瘤免疫图像分析系统检测 4 5例健康老年人 (对照组 )、36例老年炎症患者 (炎症疾病组 )、97例老年肿瘤患者 (肿瘤组 )和 30例老年肿瘤治愈患者 (肿瘤治愈组 )的外周血T淋巴细胞核仁组成区嗜银蛋白 ;应用流式细胞仪检测老年肿瘤组患者外周血T淋巴细胞表面分化抗原 (CD3、CD4、CD8)及自然杀伤细胞。　结果　与老年对照组〔(7 36± 0 76 )IS %〕及炎症疾病组〔(7 16± 1 0 4 )IS %〕相比 ,老年肿瘤组〔(5 39± 1 70 )IS %〕外周血T细胞嗜银蛋白降低 ,且差异有显著性 (P <0 0 1) ;转移性肿瘤患者嗜银蛋白下降更明显。　结论　外周血T淋巴细胞嗜银蛋白可作为老年人肿瘤的诊断和治疗监测指标。     

儿童重型β-地中海贫血同胞脐血移植后的免疫重建

目的分析儿童重型β-地中海贫血同胞脐血移植后的免疫重建情况,评价同胞脐血移植治疗重型β-地中海贫血的效果。方法11例患者移植后均为稳定骨髓植入,分别于移植后1、3、6、12、18～24、36～48个月检测患者外周血T淋巴细胞亚群（CD3^＋细胞、CD3^＋CD4^＋细胞、CD3^＋CD8^＋细胞）、B淋巴细胞（CD19^＋细胞）和自然杀伤细胞（CD3-CD56^＋NK细胞）数量,动态分析脐血移植后患者的免疫重建。结果14例患者脐血移植后11例获得植入,植入率为78．6％。11例患者移植后中性粒细胞绝对计数≥0．5×10^9／L、血小板计数≥20．0×10^9／L和≥50．0×10^9／L的中位时间分别为17、48、53d。总淋巴细胞和T淋巴细胞亚群在12个月内均恢复正常;B细胞和NK细胞分别在6个月和3个月内恢复正常。B细胞和NK细胞的恢复比T细胞快。11例患者发生急性移植物抗宿主病（GVHD）,其中I度急性GVHD9例（81．8％）,Ⅱ度急性GVHD2例（18．2％）。结论同胞脐血移植是根治重型β-地中海贫血的有效方法。     

Epigenetic regulation in antiviral innate immunity

Emerging life-threatening viruses have posed great challenges to public health. It is now increasingly clear that epigenetics plays a role in shaping host-virus interactions and there is a great need for a more thorough understanding of these intricate interactions through the epigenetic lens, which may represent potential therapeutic opportunities in the clinic. In this review, we highlight the current understanding of the roles of key epigenetic regulators — chromatin remodeling and histone modification — in modulating chromatin openness during host defense against virus. We also discuss how the RNA modification m6A (N6-methyladenosine) affects fundamental aspects of host-virus interactions. We conclude with future directions for uncovering more detailed functions that epigenetic regulation exerts on both host cells and viruses during infection.     

Long-term trend in serum (1,3)-β-D-glucan level in a man with chronic disseminated candidiasis treated with corticosteroids

Chronic disseminated candidiasis (CDC) is a type of invasive candidiasis. CDC commonly appears in the neutrophil recovery phase after chemotherapy in patients with hematologic malignancies, and immune reconstitution inflammatory syndrome (IRIS) is thought to play a major role in CDC development. This report describes the case of a 33-year-old man with CDC as a complication of acute myeloid leukemia. We describe the clinical course, body temperature, therapy, and (1,3)-β-D-glucan (BDG) levels over the course of 22 months. He was initially treated with antifungals, but corticosteroids were added because of a persistently elevated body temperature, which we attributed to IRIS. After starting corticosteroids, his clinical condition improved, but his BDG levels became markedly elevated. We hypothesize that the suppression of the excessive immune response by corticosteroids lead to granuloma collapse, fungal release, and hematogenous dissemination, resulting in elevated BDG levels. The patient's condition gradually improved over the course of follow-up.     

A simple sperm nuclear vacuole assay with propidium iodide

Our aim was to develop a new simple sperm nuclear vacuole assay (SNVA) with propidium iodide (PI) to determine the status of nuclear vacuole (NV) of individual spermatozoa. After PI staining, sperm nuclei were classified into the 14 categories according to both nuclear morphology and the status of NV. The incidence was 57.8% (range 28–84%) in fertile controls (n = 40), and 85.1% (range 67–99%) in men with varicocele (n = 40). In the fertile group, normal nuclear‐shaped spermatozoa without NV or with one small NV located in the ante‐nuclear region were significantly more in comparison with the varicocele group. In the varicocele group, abnormal nuclear‐shaped spermatozoa with one large NV and with multiple NVs located in the ante‐nuclear region were most frequent findings. Besides, spermatozoa with NVs in both ante‐ and post‐nuclear regions in the varicocele group were significantly more than those in the fertile group. In both fertile and varicocele groups, normal or abnormal nuclear‐shaped spermatozoa with one or more vacuoles only located in the post‐nuclear region occurred sparingly. The SNVA provides a useful additional approach to identify the status of NV in human spermatozoa for diagnostic purposes. A good sperm sample would have more spermatozoa without NV or with one small NV located in the ante‐nuclear region.     

肝移植术后乙肝主动免疫重建受体停用乙肝免疫球蛋白和(或)抗病毒药物的可行性

目的 探讨乙肝肝移植术后乙肝主动免疫重建成功受体停用乙肝免疫球蛋白(HBIG)和(或)抗病毒药物的可行性及临床指征.方法 检测乙肝主动免疫重建成功受体体内的HBV DNA和ccc DNA的水平,并监测其停用HBIG和(或)抗病毒药物后的乙肝复发情况.结果 共20例乙肝主动免疫重建成功受体纳入本研究.所有受体血浆均未检测到HBV DNA,1例受体的外周血单个核细胞中检测出微量HBV DNA (0.023 6 copies/cell),另1例受体的肝组织中检测出微量HBV DNA,但均未检测到ccc DNA.随访期间,所有受体均停用HBIG,13例停用抗病毒药物.1例外周血单个核细胞中检测到HBV DNA的受体有乙肝复发,并检测出HBV变异(变异位点G145R).结论 乙肝肝移植术后乙肝主动免疫重建成功受体停用HBIG和(或)抗病毒药物是安全可行的,但必须在停药前检测体内的HBV和病毒变异情况.     

Progressive multifocal leukoencephalopathy presenting with acute sensorineural hearing loss in an intestinal transplant recipient

A 20‐year‐old male presented 3.5 years after intestinal transplantation with rapidly progressive sensorineural hearing loss. Initial brain imaging was consistent with inflammation and/or demyelination. Lumbar puncture was initially non‐diagnostic and a broad infectious workup was unrevealing. Three months after presentation, a repeat LP detected JC virus for which tests had not earlier been conducted. He continued to deteriorate despite withdrawal of prior immunosuppression and addition of mirtazapine, maraviroc, and steroids. He died of progressive neurologic decompensation 5 months after his initial presentation. This case highlights progressive multifocal leukoencephalopathy (PML) as a rare complication after solid organ transplantation and acute sensorineural hearing loss as an unusual first presenting symptom of PML. JC virus should be considered in the differential diagnosis of acute sensorineural hearing loss in any immunocompromised patient.