Immunological mechanisms underlying chronic rhinosinusitis with nasal polyps

Introduction: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common and quality-of-life impacting disorder, with an underlying immunological mechanism similar to other conditions such as eosinophilic asthma or atopic eczema.

Areas covered: This review article summarizes the most recent evidence on the main immunological mechanisms involved in the pathogenesis and the perpetuation of CRSwNP, with a particular focus on the key role of epithelium-derived inflammation as a consequence of the interaction with the airborne environment.

Expert commentary: The increase in knowledge of the immunology of CRSwNP leads to the development of therapeutical strategies based upon the use of biologic agents that, according to a personalized and precision medicine approach, will provide each single patient with the most suitable immunological treatment.     

In‐vitro effect of pembrolizumab on different T regulatory cell subsets

Programmed death‐1 (PD‐1) and interactions with PD‐ligand 1 (PD‐L1) play critical roles in the tumour evasion of immune responses through different mechanisms, including inhibition of effector T cell proliferation, reducing cytotoxic activity, induction of apoptosis in tumour‐infiltrating T cells and regulatory T cell (T_reg) expansion. Effective blockade of immune checkpoints can therefore potentially eliminate these detrimental effects. The aim of this study was to investigate the effect of anti‐PD‐1 antibody, pembrolizumab, on various T_reg subpopulations. Peripheral blood mononuclear cells (PBMC) from healthy donors (HD) and primary breast cancer patients (PBC) were treated in vitro with pembrolizumab, which effectively reduced PD‐1 expression in both cohorts. We found that PD‐1 was expressed mainly on CD4⁺CD25⁺ T cells and pembrolizumab had a greater effect on PD‐1 expression in CD4⁺CD25^? T cells, compared to CD4⁺CD25⁺ cells. In addition, pembrolizumab did not affect the expression levels of T_reg‐related markers, including cytotoxic T lymphocyte antigen‐4 (CTLA‐4), CD15s, latency‐associated peptide (LAP) and Ki‐67. Moreover, we report that CD15s is expressed mainly on forkhead box P3 (FoxP3)^?Helios⁺ T_reg in HD, but it is expressed on FoxP3⁺Helios^? T_reg subset in addition to FoxP3^?Helios⁺ T_reg in PBC. Pembrolizumab did not affect the levels of FoxP3^+/?Helios^+/? T_reg subsets in both cohorts. Taken together, our study suggests that pembrolizumab does not affect T_reg or change their phenotype or function but rather blocks signalling via the PD‐1/PD‐L1 axis in activated T cells.     

The opposing roles of CD4+ T cells in anti‐tumour immunity

Cancer immunotherapy focuses mainly on anti‐tumour activity of CD8⁺ cytotoxic T lymphocytes (CTLs). CTLs can directly kill all tumour cell types, provided they carry recognizable antigens. However, CD4⁺ T cells also play important roles in anti‐tumour immunity. CD4⁺ T cells can either suppress or promote the anti‐tumour CTL response, either in secondary lymphoid organs or in the tumour. In this review, we highlight opposing mechanisms of conventional and regulatory T cells at both sites. We outline how current cancer immunotherapy strategies affect both subsets and how selective modulation of each subset is important to maximize the clinical response of cancer patients.     

Interferon‐γ, Interleukins‐6 and ‐4, and Factor XIII‐A as Indirect Markers of the Classical and Alternative Macrophage Activation Pathways in Chronic Periodontitis

Background: Macrophages account for 5% to 30% of the inflammatory infiltrate in periodontitis and are activated by the classic and alternative pathways. These pathways are identified by indirect markers, among which interferon (IFN)‐γ and interleukin‐6 (IL)‐6 of the classic pathway and IL‐4 of the alternative pathway have been studied widely. Recently, factor XIII‐A (FXIII‐A) was reported to be a good marker of alternative pathway activation. The aim of this study is to determine the macrophage activation pathways involved in chronic periodontitis (CP) by the detection of the indirect markers IFN‐γ, IL‐6, FXIII‐A, and IL‐4. Methods: Biopsies were taken from patients with CP (n = 10) and healthy individuals (n = 10) for analysis of IFN‐γ, IL‐6, IL‐4, and FXIII‐A by Western blot (WB), immunohistochemistry (IHC), and enzyme‐linked immunosorbent assay (ELISA). The same biopsies of healthy and diseased gingival tissue were used, and the expressions of these markers were compared between healthy individuals and those with CP. Results: The presence of macrophages was detected by CD68+ immunohistochemistry and their IFN‐γ, IL‐6, IL‐4, and FXIII‐A markers by WB, IHC, and ELISA in all samples of healthy and diseased tissue. IL‐6, IL‐4, and FXIII‐A were significantly higher in patients with CP, whereas FXIII‐A was higher in healthy individuals. Conclusion: The presence of IFN‐γ, IL‐6, IL‐4, and FXIII‐A in healthy individuals and in patients with CP suggests that macrophages may be activated by both classic and alternative pathways in health and in periodontal disease.     

银苓Ⅰ号对铅中毒小鼠非特异免疫功能的影响

目的:探讨中药复方银苓Ⅰ号对铅中毒小鼠非特异免疫功能的影响。方法:小鼠自由饮用醋酸铅溶液造模,分别予银苓Ⅰ号或依地酸钠钙治疗3周;观察外周血弊细胞计数、碳粒廓清指数K及校正指数α、免疫脏器指数等非特异性免疫功能指标的变化。结果:银苓Ⅰ号对外周血白细胞计数、碳粒廓清指数K及校正指数α、免疫脏器指数有明显改善作用,而且碳粒廓清能力优于依地酸钠钙。结论:银苓号可在一定程度上对抗铅中毒所致的非特异免疫损害,效果优于依地酸钠钙。     

CD4+CD25highT细胞在小细胞肺癌患者外周血中的表达及意义

目的探讨CD4+CD25high调节(抑制)性T细胞在小细胞肺癌患者外周血中的表达情况及其意义.方法应用流式细胞技术检测40例初诊小细胞肺癌患者,18例CE及CAP方案交替化疗后完全缓解的小细胞肺癌患者外周血中的CD4+CDhighT细胞,计算它们占CD4+T细胞的比率.结果初诊小细胞肺癌患者CD4+CD25highT细胞占CD4+T细胞的比率(6.69±2.32)%,高于健康对照组(4.13±1.25)%(P＜0.01);经化疗后完全缓解的小细胞肺癌患者外周血CD4+CD25highT细胞占CD4+T细胞的比率与初诊时相比无明显变化.结论小细胞肺癌患者外周血中CD4+CD25high调节T细胞占CD4+T细胞的比率增高,它们对小细胞肺癌患者具有免疫抑制作用.     

肺炎衣原体感染与急性脑梗死的相关性

目的:探讨肺炎衣原体(Cpn)感染与急性脑梗死发生发展的关系。方法:采用微量免疫荧光法(M IF)检测100例急性脑梗死患者(病例组)与100例同期门诊健康体检者(对照组)肺炎衣原体血清特异性IgG、IgM抗体,并使用全自动生化仪检测血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)浓度及C-反应蛋白(CRP)水平。结果:病例组和对照组肺炎衣原体慢性感染率分别为72.0%、50.0%,差异有显著性(P<0.01)。急性感染率分别为15.0%、12.0%,两组差异无显著性(P>0.05)。病例组血脂水平:TC(6.1±1.48)mm o l/L,TG(2.69±1.91)mm o l/L,LDL-C(3.85±0.25)mm o l/L,HDL-C(1.03±0.56)mm o l/L;对照组TC、TG、LDL-C、HDL-C水平分别为(4.22±0.43)mm o l/L,(1.08±0.25)mm o l/L,(2.48±0.65)mm o l/L,(1.15±0.59)mm o l/L;两组CRP水平分别为:(13.72±5.30)m g/L,(5.61±2.4)m g/L;两组在血脂、CRP水平比较差异有显著性(P<0.01)。在病例组中,肺炎衣原体阳性者(感染组)血清TC、TG浓度及CRP水平高于阴性者(非感染组)(P<0.05),HDL-C浓度略低于非感染组,但差异无显著性(P>0.05)。结论:肺炎衣原体慢性感染与脑梗死发病有一定的相关性,血清中的CRP和肺炎衣原体抗体水平升高提示炎症反应增强。     

类风镇痛Ⅰ号治疗类风湿性关节炎的临床研究

目的:观察中药类风镇痛Ⅰ号冲剂治疗类风湿性关节炎的临床疗效,从免疫学方向探讨中西医结合治疗类风湿性关节炎的作用机制.方法:将70例类风湿性关节炎患者随机分为治疗组(类风镇痛Ⅰ号与常规西药联用)36例,对照组(单纯西药)34例,治疗2个月后比较两组临床疗效以及主要症状、体征的变化,检测常规类风湿性关节炎临床指标、免疫球蛋白、淋巴细胞因子如白细胞介素-6及其受体(IL-6、IL-6R)、IL-8和肿瘤坏死因子-α(TNF-α)水平的变化.结果:治疗组主要症状与体征的改善及疗效的总有效率均明显优于对照组(P<0.05或P<0.01),免疫球蛋白IgG、血沉、IL-8和TNF-α下降幅度也明显大于对照组(P<0.05或P<0.01).结论:类风镇痛Ⅰ号能提高类风湿性关节炎的临床疗效,减少西药的不良反应,具有调节机体免疫功能,改善类风湿性关节炎免疫损伤等多种综合效应.