原发性干燥综合征患者肠道菌群特征分析

通过比较原发性干燥综合征(pSS)患者和健康人群肠道菌群的差异, 深入探讨pSS患者肠道菌群与pSS发生发展的关系。

招募2019年1月至2021年2月于大连市中心医院风湿免疫科住院的pSS患者60名, 作为本研究的pSS组; 同时招募大连市中心医院体检中心的健康志愿者50名作为本研究的对照组(Control组)。收集两组粪便标本, 各50例, 提取细菌DNA进行16S rDNA高通量测序后进行菌群多样性和LEfSe分析。

pSS组肠道菌群α-多样性较Control组显著降低(P < 0.05)。与Control组相比, pSS组厚壁菌门/拟杆菌门比值降低; 普雷沃菌科、红蝽菌科、消化链球菌科、Eggerthellaceae, unidentified_Clostridiales丰度降低, 而拟杆菌科升高; 罗姆布茨菌属和Dorea等丰度降低, 拟杆菌属、韦荣球菌属等丰度升高。并且在pSS组肠道菌群中发现大肠埃希菌丰度明显升高。

pSS患者存在肠道菌群失调, 提示菌群失调可能与pSS的发生发展有关。

     

IgM memory and Waldenstr?m macroglobulinemia’s cell of origin

Waldenström macroglobulinemia (WM) is a neoplasm of mature IgM-expressing B-lymphocytes that is characterized by the occurrence of a monoclonal IgM (mIgM) paraprotein in blood serum and the infiltration of hematopoietic bone marrow with malignant lymphoplasmacytic cells. WM remains incurable despite the development of new therapeutic options. Owing in large measure to having a low incidence, indolent clinical course and good long-term control with proper clinical management, WM has not been investigated as extensively as other B-lineage neoplasms. Major knowledge gaps in our understanding of the natural history of WM include the cell of origin. With that shortcoming in mind, here we discuss the significance of a specific gain-of-function mutation in the adapter protein, myeloid differentiation primary response 88 (MYD88), that occurs with near-complete penetrance in WM and suggests that tumor development is under strong selective pressure for elevated MYD88 signaling. This provides an intriguing link to IgM memory B-cells, which comprise two types of B-lymphocytes ( natural effector IgM⁺IgD⁺ cells and IgM^-only IgM⁺IgD^- cells ) that depend, in part, on MYD88 signaling and constitute intriguing candidates for WM’s cell of origin. We review the features and developmental history of IgM memory in greater depth and propose that WM may be derived from primitive innate-like B-cells ( marginal zone B-cells and B1 B-cells ) that feed the IgM memory compartment. We conclude with a model of MYD88-dependent tumor development in the mature B-cell lineage that considers two different ( convergent or divergent) oncogenesis pathways with respect to the cells of origin.     

肠道菌群与过敏性紫癜性肾炎患儿肾功能及免疫功能的相关性研究

探讨肠道菌群与过敏性紫癜性肾炎患儿肾功能及免疫功能的相关性研究。

选取2021年9月—2023年9月于本院治疗的85例过敏性紫癜性肾炎患儿,标记为研究组。并纳入同期进行健康体检的68例同年龄段健康儿童作为对照组。采集患者空腹静脉血和粪便,采用qRT-PCR法定量分析肠道中大肠杆菌和双歧杆菌的数量,计算双歧杆菌/大肠杆菌（B/E）比值。使用全自动特定蛋白分析系统ARRAY360和流式细胞仪检测IgM、IgG、IgA、外周血CD4⁺ T淋巴细胞和CD8⁺ T淋巴细胞,计算CD4⁺/CD8⁺比值。过敏性紫癜性肾炎患儿肠道菌群与肾功能及免疫功能之间的相关性分析采用Pearson分析。

两组的性别、年龄、体质量指数差异均无统计学意义（P＜0.05）。与对照组相比,研究组大肠杆菌数量增加（P＜0.05）,血肌酐、尿素氮、血清尿酸、IgM、IgG、IgA、CD8⁺ T细胞水平升高（P＜0.05）,但双歧杆菌数量降低（P＜0.05）,B/E比值、CD4⁺ T细胞、CD4⁺/CD8⁺比值显著降低（P＜0.05）。过敏性紫癜性肾炎患儿肠道中的大肠杆菌数量分别与血肌酐、尿素氮、血清尿酸、IgM、IgG、IgA、CD8⁺ T细胞水平呈正相关（P＜0.001）,与CD4⁺ T细胞水平、CD4⁺/CD8⁺比值呈负相关（P＜0.001）;双歧杆菌、B/E比值分别与血肌酐、尿素氮、血清尿酸、IgM、IgG、IgA、CD8⁺ T细胞水平呈负相关（P＜0.001）,与CD4⁺ T细胞、CD4⁺/CD8⁺比值呈正相关（P＜0.001）。

过敏性紫癜性肾炎患儿肠道B/E比值显著降低,并与其肾功能及免疫功能指标存在相关性。

     

Waldenstr?m macroglobulinemia – immunophenotype and natural history

Despite encouraging progress in recent years, our knowledge of the natural history of Waldenström macroglobulinemia (WM), a low-grade LPL (lymphoplasmacytic lymphoma) of mature IgM⁺ B-lymphocytes, remains superficial. This is particularly true of the etiology of WM (tumor causation and initiation) and the sequence of events that underlie the malignant transformation of precursor B cells (tumor progression). Here we briefly review the epidemiology of and genetic predisposition to WM and consider the role of autoimmunity and chronic inflammation in related tumor development. We discuss the immunophenotypic features of WM, including the immunological specificity of WM-associated IgM paraproteins. The proclivity of patients with WM to develop the rare immunoglobulin autoantibody syndromes mixed IgM-IgG cryoglobulinemia, chronic cold agglutinin disease, and IgM neuropathy will also be discussed. We conclude with a call for additional research to elucidate outstanding questions, such as the role of T cell-dependent vs. –independent immune responses in the pathophysiology of WM.