RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Hypersensitivity to mosquito bites: A versatile Epstein-Barr virus disease with allergy, inflammation, and malignancy.
Hypersensitivity to mosquito bites: A versatile Epstein-Barr virus disease with allergy, inflammation, and malignancy.
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蚊虫叮咬超敏反应(HMB)是一种罕见疾病,表现为短暂而剧烈的皮肤反应及全身炎症。其临床表现类似其他蚊虫过敏反应,有时也难以与其他严重过敏反应区分,但其背后有独特的病理生理机制。HMB属于爱泼斯坦-巴尔病毒(EBV)相关自然杀伤(NK)细胞淋巴增殖性疾病(LPD)。因此,HMB可能进展为噬血细胞性淋巴组织细胞增多症、慢性活动性EBV病及EBV相关恶性肿瘤等系统性疾病。患者常同时出现血清IgE升高、NK细胞增多以及外周血EBV DNA阳性;检出EBV感染的NK细胞通常有助于诊断。然而,目前有效治疗手段有限,确切病因仍不清楚。蚊虫叮咬引发的局部CD4+ T细胞增殖似乎会促进EBV再激活及EBV感染的NK细胞增殖。这些免疫相互作用或可解释HMB症状为何短暂,以及疾病如何进展为恶性LPD。仍需进一步研究以阐明HMB机制,从而改善HMB及其他EBV相关LPD的诊断和治疗。
Hypersensitivity to mosquito bites (HMB) is a rare disease characterized by transient intense skin reaction and systemic inflammation. Clinical presentation of HMB resembles other mosquito allergic responses, and it can also be difficult to clinically distinguish HMB from other severe allergic reactions.
However, a distinctive pathophysiology underlies HMB. HMB belongs to a category of Epstein-Barr virus (EBV)-associated natural killer (NK) cell lymphoproliferative disorders (LPD). Hence, HMB may progress to systemic diseases, such as hemophagocytic lymphohistiocytosis, chronic active EBV disease, and EBV-associated malignancies. A triad of elevated serum IgE, NK lymphocytosis, and detection of EBV DNA in peripheral blood is commonly observed, and identification of EBV-infected NK cells usually facilitates the diagnosis.
However, the effective treatment is limited, and its precise etiology remains unknown. Local CD4+ T cell proliferation triggered by mosquito bites appears to help induce EBV reactivation and EBV-infected NK-cell proliferation. These immunological interactions may explain the transient HMB signs and symptoms and the disease progression toward malignant LPD.
Further research to elucidate the mechanism of HMB is warranted for better diagnosis and treatment of HMB and other forms of EBV-associated LPD.
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