Extensive immune-mediated hippocampal damage in mice surviving infection with neuroadapted Sindbis virus

Viral infections of the central nervous system and immune responses to these infections cause a variety of neurological diseases. Infection of weanling mice with Sindbis virus causes acute nonfatal encephalomyelitis followed by clearance of infectious virus, but persistence of viral RNA. Infection with a neuroadapted strain of Sindbis virus (NSV) causes fatal encephalomyelitis, but passive transfer of immune serum after infection protects from fatal disease and infectious virus is cleared. To determine whether persistent NSV RNA is associated with neurological damage, we examined the brains of recovered mice and found progressive loss of the hippocampal gyrus, adjacent white matter, and deep cerebral cortex associated with mononuclear cell infiltration. Mice deficient in CD4(+) T cells showed less tissue loss, while mice lacking CD8(+) T cells showed lesions comparable to those in immunocompetent mice. Mice deficient in both CD4(+) and CD8(+) T cells developed severe tissue loss similar to immunocompetent mice and this was associated with extensive infiltration of macrophages. The number of CD4(+) cells and macrophage/microglial cells, but not CD8(+) cells, infiltrating the hippocampal gyrus was correlated with the number of terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling positive pyramidal neurons. These results suggest that CD4(+) T cells can promote progressive neuronal death and tissue injury, despite clearance of infectious virus.     

EBV感染患儿临床特征及血清免疫因子水平

目的分析124例巴尔病毒(EBV)感染患儿的临床特征和血清免疫因子水平。方法选择2016年12月-2019年12月于海南医学院第一附属医院确诊的124例EBV感染患儿为研究组,根据临床表现分为传染性单核细胞增多症(IM)组43例和单纯性EBV组81例,选择同期健康体检儿童62名为对照组。记录所有患儿入组时的年龄、性别、临床症状;荧光定量PCR反应检测外周血淋巴细胞中EBV DNA载量;检测血清白细胞介素-6(IL-6)、IL-2和肿瘤坏死因子-α(TNF-α)水平,流式细胞仪分析外周血T淋巴细胞水平;Pearson相关性分析外周血T淋巴细胞亚群与EBV DNA载量之间的相关性。结果 IM组患儿的年龄为(5.13±1.56)岁,大于单纯性EBV组(P<0.05),出现发热、咽峡炎、淋巴结肿大、脾肿大、肝肿大、眼睑水肿、鼻塞、打鼾的比例为88.37%、93.02%、93.02%、48.84%、60.47%、32.56%、55.81%和46.51%,高于单纯性EBV组(P<0.05);IM组患儿的血CD3+T、CD8+T细胞、IL-6、TNF-α为分别为(73.25±7.16)%、(40.19±4.21)%、(33.68±5.71)ng/L、(72.52±11.26)ng/L高于对照组,而CD4+T、CD4+/CD8+T细胞、IL-2分别为(34.86±3.75)%、(0.89±0.15)、(10.43±3.38)ng/L则均低于对照组(P<0.05);外周血CD3+T和CD8+T细胞水平均与病毒载量呈正相关(r=0.314,0.447,P<0.05),CD4+T和CD4+/CD8+T细胞水平与病毒载量呈负相关(r=-0.425,-0.376,P<0.05)。结论 EBV感染患儿的临床症状和细胞免疫功能与病毒载量有关,有望应用于临床评估EBV感染的病情发展。     

Scientific connotation of “treating different diseases with the same method” from the perspective of metabolic–immune dysregulation in inflammation-mediated carcinogenesis of digestive organs

Inflammation-mediated carcinogenesis develops in the context of chronic inflammation and is a significant cause of cancer within the digestive system. In the chronic inflammation microenvironment, the metabolic activity of tissue cells undergoes extensive changes, which interfere with the normal function of immune cells. Dysregulation of cell metabolism and immune function has been identified as a key factor contributing to inflammation-mediated carcinogenesis within the major digestive organs, such as the stomach, liver, and colorectum. This metabolic–immune imbalance also corresponds to traditional Chinese medicine (TCM) theories of “yin-yang disharmony” and “disharmony between Ying-nutrients and Wei-defense.” The metabolic–immune imbalance has also been regarded as the key factor supporting “treatment of different diseases with the same method,” in which the same approach is adopted in the treatment of different conditions. In the TCM treatment process, it is necessary to first identify TCM patterns and then apply the corresponding TCM to correct the dysregulated metabolic and immune function, thereby blocking the progression from inflammation to malignancy. Our study findings deepen the TCM understanding of metabolic–immune dysregulation and the relationship between metabolic–immune dysregulation, pattern identification, and treatment method. They also provide new insights for the treatment of inflammation-mediated carcinogenesis in major digestive organs and help us further explore the scientific connotation of the TCM strategy of “treating different diseases with the same method.     

Long-term survivors following autologous haematopoetic stem cell transplantation have significant defects in their humoral immunity against vaccine preventable diseases,years on from transplant

Current international guidelines recommend routinely vaccinating haematopoetic stem cell transplant (HSCT) recipients. Despite significant infection-related mortality following autologous HSCT, routine vaccination programmes (RVP) completion is poor. For recovered HSCT recipients, it is uncertain whether catch-up vaccination remains worthwhile years later.To determine potential susceptibility to vaccine preventable infections, we measured antibody titres in 56 patients, a median of 7 years (range 0–29) following autologous HSCT, who had not completed RVP. We found that almost all participants had inadequate titres against diphtheria (98.2%) and pneumococcal infection (100%), and a significant proportion had inadequate titres against measles (34.5%). Of those subsequently vaccinated according to available guidelines, many mounted adequate serological responses.These data suggest a pragmatic catch-up approach for autologous HSCT recipients who have not completed RVP is advisable, with universal vaccination against some pathogens (e.g. Streptococcus pneumoniae and diphtheria) and serologically-guided approaches for others (e.g. measles and varicella zoster virus).     

Serological response with Heplisav-B® in prior Hepatitis B vaccine non-responders living with HIV

BackgroundAs people living with HIV (PLWH) are at risk for contracting Hepatitis B Virus (HBV), they should be screened for HBV and vaccinated if not immune. Seroconversion rates in PLWH receiving traditional recombinant HBV vaccines (Engerix-B® and Recombivax-HB®) have historically been low with at most 70% achieving immunity. In 2017, a recombinant, adjuvanted HBV vaccine (Heplisav-B®) was approved for use in HIV-negative patients.Heplisav-B® has shown superior seroprotection in this population compared to Engerix-B® and Recombivax-HB®, as well as interim analysis showing higher seropositivity rates in patients undergoing dialysis. However, its efficacy in PLWH is currently unknown. This study evaluates the rate of seroconversion following Heplisav-B® administration in PLWH with previous HBV vaccination failure.MethodsRetrospective, cross-sectional study at The Brooklyn Hospital Center’s HIV primary care clinic in Brooklyn, NY. HIV-positive adults who received at least two doses of Heplisav-B® and had previously failed to seroconvert after vaccination with Engerix-B® or Recombivax-HB® were included. The primary outcome is the percentage of PLWH who became seropositive following Heplisav-B®.ResultsA total of 67 patients met the inclusion criteria. Twenty-five (37.3%) PLWH had failed at least 2 courses of recombinant vaccines. Fifty-eight (86.6%) PLWH became seropositive (Anti-HBs > 10 mIU/mL) at least two months after completing Heplisav-B®. For the 9 (13.4%) patients that did not develop immunity, 3 (33%) had a detectable HIV RNA and 3 (33%) had a CD4 count < 200 cells/uL³.ConclusionsHeplisav-B® was highly effective in achieving immunity to HBV in PLWH who failed non-adjuvanted recombinant vaccines.     

百球清（Baycox）对柔嫩艾美尔球虫的作用以及对球虫免疫力影响的研究

进行四项试验观察Ｂａｙｃｏｘ对柔嫩艾美尔球虫的作用及其对球虫免疫力影响。Ｂａｙｃｏｘ均以推荐浓度（２５ｐｐｍＴｏｌｔｒａｚｕｒｉｌ）混入水中任鸡自由饮用。以２０００卵囊剂量感染并立即给药的鸡，在感染后６－２０ｄ粪便中始终没有发现卵囊，表明Ｂａｙｏｏｘ具有杀虫作用而不是抑虫作用。以８×１０￣４卵囊剂量感染鸡，在感染前１ｄ和感染后０、１、２、３、４、５ｄ分别开始给药，根据血便数量和盲肠病变判断，Ｂａｙｃｏｘ的作用峰期是在感染后０－２ｄ之间。感染后第４ｄ再给药已无治疗作用。停药１ｄ后，药物残效对感染仍显出一定的抗球虫作用，但是停药２ｄ后，这种作用即基本消失。采用攻毒的方法表明Ｂａｙｃｏｘ不影响抗球虫免疫力的形成。     

Requirement of HMGB1 and RAGE for the maturation of human plasmacytoid dendritic cells

Dendritic cells (DC) are key components of innate and adaptive immune responses. Plasmacytoid DC (PDC) are a specialized DC subset that produce high amounts of type I interferons in response to microbes. High mobility group box 1 protein (HMGB1) is an abundant nuclear protein, which acts as a potent pro-inflammatory factor when released extracellularly. We show that HMGB1 leaves the nucleus of maturing PDC following TLR9 activation, and that PDC express on the plasma membrane the best-characterized receptor for HMGB1, RAGE. Maturation and type I IFN secretion of PDC is hindered when the HMGB1/RAGE pathway is disrupted. These results reveal HMGB1 and RAGE as the first known autocrine loop modulating the maturation of PDC, and suggest that antagonists of HMGB1/RAGE might have therapeutic potential for the treatment of systemic human diseases.     

原发性肝癌经皮微波凝固治疗前后局部免疫活性细胞功能检测

目的：了解原发性肝癌经皮微波凝固治疗前、后局部免疫活性细胞功能变化。方法：C地38例病理诊断原发性肝癌,并接受超声导引下经皮微波凝固治疗的患者。分别治疗前及治疗后17d,超声导引下经皮用18G组织切割针于病灶及其周边肝组织取活检标本,取出的组织标本石蜡包埋,采用特异性单克隆抗体免疫组织化学染色,检测CD3^ 、CD56^ 、CD68^ 细胞及T淋巴细胞表面Fas配体;并在光镜下观察,用病理图像分析仪测量治疗前后、后阳性细胞直径、阳性细胞占单位面积百分比、T淋巴细胞Fas-L阳性表达率及治疗前后巨噬细胞内次级溶酶体变化。结果：治疗前肿瘤内仅有少量免疫细胞浸润,多数浸润的CD3^ 和CD56^ 细胞最大径小于10μm,CD68^ 细胞最大径小于18μm。治疗后病灶内浸润的CD3^ 、CD56^ 和CD68^ 细胞数量较治疗前明显增加,细胞体积明显增大（同治疗前相比CD3^ 细胞和CD56^ 细胞t和P值分别为3．48,－4．76和0．025,0．000,巨噬细胞t和P值分别为－2．46和0．028）。最大径大于10μm的CD3^ 和CD56^ 细胞分别由治疗前的10．4％和20．1％增至24．9％和30．2％,最大径大于18μm的CD68^ 细胞由10．2％增至33．4％。T淋巴细胞Fas-L阳性率由治疗前的7．2％增高至20．1％（P＜0．01,巨噬细胞内次级溶酶体和T淋巴细胞内细胞器明显增多。结论：原发性肝癌经皮微波凝固治疗提高局部浸润免疫细胞的功能。     

喉癌围手术期细胞免疫功能改变的意义

目的：了解喉癌患者围手术期细胞免疫的状况及手术相关因素对患者细胞免疫的影响;了解T淋巴细胞水平与喉癌临床特征,病程进展的关系。方法：应用SAP法检测喉癌术前2d及术后12d外周血CD3^ ,CD4^ ,CD8^ 细胞水平及CD4^ ／CD8^ 比率的改变,并联系临床分期、淋巴结转移,复发综合分析。结果：喉癌患者CD3^ ,CD4^ ,CD8^ 细胞水平及CD4^ ／CD8^比正常对照组明显下降;术后CD3^ ,CD4^ ,CD8^ 有进一步下降的倾向。晚期喉癌患者CD4^＋细胞水平,CD4^ ／CD8^ 比率明显下降（P＜0．05）。淋 巴结转移者CD4^ ／CD8^ 亦下降,CD8^ 细胞水平却相对升高;复发患者的CD8^ 细胞水平相对提高。结论：喉癌患者T淋 巴细胞免疫功能低下,全麻、手术创伤及术后复合因素是喉癌术后免疫功能进一步低下的原因。CD4^ ,CD8^ 细胞水平及CD4^ ／CD8^ 比率是表明喉癌患者病期进展,淋巴结转移,复发的免疫学指标,围手术期需行免疫治疗。     

Study of some immunological signatures and their association with COVID-19 in a sample of recovered Iraqi patients

Since its emergence about two years ago, the novel coronavirus has continued to be a challenge and threat to public health, struck most parts of the world, leaving more than half a billion cases of infection and more than five million deaths. Immune response abnormalities post-infection with SARS-CoV-2 have been reported, and the mechanisms that lead to them are still ambiguous. This study was conducted to evaluate some immunological markers in the serum samples of COVID-19 convalescent patients and investigate the association of these immunological signatures with their age and sex. The serum levels of immunoglobulin G, interleukin-1 beta, and interferon lambda-1 of 75 patients and 50 healthy control group members were measured, with 55 % males and 45 % females participating and ages ranging from 20 to 80 years. The measurement of the immunological signatures was performed using the enzyme-linked immunosorbent assay (ELISA). The result revealed highly significant elevated levels of the serum immunological signatures of the convalescent group in comparison to the control group, with P-values of 0.00001 for each signature. Moreover, age was observed to have an association with an elevated level of the immunological signatures as it increased in the elderly, whereas no association with sex was detected. The findings strongly suggest that COVID-19 infection results in a persistent inflammatory response, which leads to prolonged post-recovery symptoms. Post-COVID-19 syndrome necessitates additional research to clarify its pathophysiology, pathogenesis, and long-term implications.