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1.
《Vaccine》2022,40(41):5892-5903
To control the coronavirus disease 2019 (COVID-19) pandemic, there is a need to develop vaccines to prevent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. One candidate is a nasal vaccine capable of inducing secretory IgA antibodies in the mucosa of the upper respiratory tract, the initial site of infection. However, regarding the development of COVID-19 vaccines, there is concern about the potential risk of inducing lung eosinophilic immunopathology as a vaccine-associated enhanced respiratory disease as a result of the T helper 2 (Th2)-dominant adaptive immune response. In this study, we investigated the protective effect against virus infection induced by intranasal vaccination of recombinant trimeric spike protein derived from SARS-CoV-2 adjuvanted with CpG oligonucleotides, ODN2006, in mouse model. The intranasal vaccine combined with ODN2006 successfully induced not only systemic spike-specific IgG antibodies, but also secretory IgA antibodies in the nasal mucosa. Secretory IgA antibodies showed high protective ability against SARS-CoV-2 variants (Alpha, Beta and Gamma variants) compared to IgG antibodies in the serum. The nasal vaccine of this formulation induced a high number of IFN-γ-secreting cells in the draining cervical lymph nodes and a lower spike-specific IgG1/IgG2a ratio compared to that of subcutaneous vaccination with alum as a typical Th2 adjuvant. These features are consistent with the induction of the Th1 adaptive immune response. In addition, mice intranasally vaccinated with ODN2006 showed less lung eosinophilic immunopathology after viral challenge than mice subcutaneously vaccinated with alum adjuvant. Our findings indicate that intranasal vaccine adjuvanted with ODN2006 could be a candidate that can prevent the infection of antigenically different variant viruses, reducing the risk of vaccine-associated enhanced respiratory disease.  相似文献   
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ObjectiveTo study the clinical features and identify unique renal neoplasia subtypes and their prognostic implications in individuals with tuberous sclerosis complex (TSC).Patients and MethodsThe Mayo Clinic nephrectomy registry included 37 patients with TSC diagnosed between 1970 and 2018. Four additional patients were identified from the pathology consultation and autopsy files. All available renal tumors were further characterized using immunohistochemistry and fluorescence in situ hybridization. Clinicopathologic features and follow-up were obtained from the medical record. The American Association for Cancer Research Project GENIE registry was accessed using cBioPortal for molecular profiling of angiomyolipoma (AML).ResultsA total of 276 renal tumors from 41 patients were analyzed. Renal tumors were classified into 9 distinct morphological subtypes, with AML predominating (238 [86%]). Interestingly, all these tumors acted in a benign fashion except one renal cell carcinoma with clear cells and fibromyomatous stroma and one epithelioid AML that metastasized. Molecular profiling studies revealed that epithelioid AMLs were enriched for alterations of TP53, RB1, and ATRX. Eight patients died of direct complications of TSC, including 3 of end-stage renal disease. To date, none have died of a renal epithelial neoplasm.ConclusionThe identification of unique renal neoplasia subtypes may provide important clues to establish a diagnosis of TSC, and in the somatic setting, this finding has important implications for accurate prognostication. These tumors tend to be indolent, and only 2 of 276 tumors in our study exhibited metastatic behavior. Our results support multidisciplinary management with a focus on preservation of renal function.  相似文献   
3.
Three human protoparvoviruses, bufavirus (BuV), tusavirus (TuV) and cutavirus (CuV), have recently been discovered in diarrheal stool. BuV has been associated with diarrhea and CuV with cutaneous T-cell lymphoma, but there are hardly any data for TuV or CuV in stool or respiratory samples. Hence, using qPCR and IgG enzyme immunoassays, we analyzed 1072 stool, 316 respiratory and 445 serum or plasma samples from 1098 patients with and without gastroenteritis (GE) or respiratory-tract infections (RTI) from Finland, Latvia and Malawi. The overall CuV-DNA prevalences in stool samples ranged between 0–6.1% among our six patient cohorts. In Finland, CuV DNA was significantly more prevalent in GE patients above rather than below 60 years of age (5.1% vs 0.2%). CuV DNA was more prevalent in stools among Latvian and Malawian children compared with Finnish children. In 10/11 CuV DNA-positive adults and 4/6 CuV DNA-positive children with GE, no known causal pathogens were detected. Interestingly, for the first time, CuV DNA was observed in two nasopharyngeal aspirates from children with RTI and the rare TuV in diarrheal stools of two adults. Our results provide new insights on the occurrence of human protoparvoviruses in GE and RTI in different countries.  相似文献   
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慢性嗜酸性粒细胞型鼻窦炎(ECRS)是以嗜酸性粒细胞浸润为特征的呼吸道黏膜炎性疾病。嗜酸性粒细胞是一种特殊的炎症细胞,与Th2型免疫反应密切相关。促进和维持ECRS患者嗜酸性炎症的机制主要有以下4个方面:白介素-5(IL-5)调控嗜酸性粒细胞的生物学效应、嗜酸性粒细胞胞外陷阱的免疫调节作用、细胞自噬调节和纤维蛋白异常沉积。ECRS表现出病因复杂、难治愈和易复发等特点,嗜酸性粒细胞在ECRS的发生发展中扮演着重要的角色。本文就国内外最新报道进行综述,以期为ECRS的治疗提供理论依据。  相似文献   
7.
目的 探讨临床药师在识别药物不良反应(ADR)中的作用,提醒临床注意重组人粒细胞刺激因子引起药物性肺损伤的可能,并与感染性疾病相鉴别。方法 对1例粒细胞降低患者因使用重组人粒细胞刺激因子出现急性肺损伤的病例进行分析,评估重组人粒细胞刺激因子与急性嗜酸性粒细胞肺炎的关联并分析可能的机制。同时,临床药师对患者病情进行评估和判断,提出相应的治疗建议。结果 患者使用重组人粒细胞刺激因子后嗜酸性粒细胞增高,双肺炎症加重,抗感染治疗效果不佳,考虑为重组人粒细胞刺激因子相关嗜酸性粒细胞肺炎,及时停用抗感染及抗病毒药物,并予糖皮质激素治疗后,患者肺部症状好转,嗜酸性粒细胞恢复正常。结论 重组人粒细胞刺激因子可引起罕见嗜酸性粒细胞肺炎,临床药师参与临床治疗有助于提高对药源性疾病的识别和管理,从而调整治疗方向,保证临床治疗成功。  相似文献   
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Introduction: Primary atopic disorders can be classified as heritable genetic disorders presenting with deregulated pathogenic allergic effector responses irrespective of sensitization. In the last decade, there are parallel rises in the burden of atopic and gastrointestinal (GI) diseases.

Areas covered: There is increasing recognition of an association between atopy and GI disease through immune dysregulation, the microbiome and shared genetic pathways. Since the first article on atopy and the GI tract in 2014 in this journal, many more studies have shed light on the shared pathways in these diseases, particularly in the field of eosinophilic GI disease, functional GI disorders, and inflammatory bowel disease.

Expert opinion: Understanding the links with common mechanisms in atopy and GI diseases that may lead to better targeting of treatment through manipulation of immune mechanisms, the microbiome, genetics, food allergens and specific GI diseases such as inflammatory bowel disease, functional GI disorders.  相似文献   

10.

Background

IgG4 production is regulated by type 2 (IL-4 and IL-13) and regulatory (IL-10) cytokines involved in the pathophysiology of chronic rhinosinusitis (CRS). We sought to determine the pathophysiological characteristics of IgG4-positive cells in sinonasal tissues in CRS, especially eosinophilic CRS (ECRS).

Methods

IgG4-positive cells in uncinate tissues (UT) and nasal polyps (NP) were examined by immunohistochemistry. Associations between the number of IgG4-positive cells and clinicopathological factors were analyzed. Receiver operating characteristics (ROC) analysis was performed to determine the cut-off value of IgG4-positive cells in tissue that can predict the post-operative course.

Results

IgG4 was mainly expressed in infiltrating plasma and plasmacytoid cells, and the number of IgG4-positive cells was significantly higher in NP, especially those from severe ECRS patients, than in UT. In CRS patients, the number of IgG4-positive cells significantly and positively correlated with blood and tissue eosinophilia, radiological severity, and serum level of total IgE. The number of infiltrating IgG4-positive cells was significantly higher in patients with a poor post-operative course (sustained sinus shadow 6 months after surgery) than in those with a good one. The number of IgG4-positive cells in NP could discriminate patients with a good or a poor post-operative course (area under the curve: 0.769). Also, 73.3% sensitivity and 82.5% specificity were achieved when the cut-off value was set at 17 cells/high-power field.

Conclusions

Our results suggest that the local expression of IgG4 on cells may be used as a biomarker that reflects the pathophysiology of CRS, including the post-operative course.  相似文献   
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