Association of vitamin D levels and risk of latent tuberculosis in the hemodialysis population

BackgroundVitamin D is essential in the host defense against tuberculosis (TB). Suboptimal vitamin D status is common in the hemodialysis population. Hemodialysis patients have an increased risk compared to the general population latent tuberculosis infection (LTBI). However, the association between vitamin D deficiency and LTBI in this population remains unclear.Materials and methodsWe conducted a cross-sectional study between March and May 2017. Interferon-gamma release assay (IGRA) through QuantiFERON-TB Gold In-Tube was used to assess LTBI. Plasma 25-hydroxycholecalciferol (25-OHD) levels were measured by Elecsys Vitamin D Total assay. Suboptimal vitamin D levels included vitamin D insufficiency 20–29 ng/mg and vitamin D deficiency <20 ng/mL. Predictors for LTBI were analyzed.ResultsA total of 287 participants were enrolled. The suboptimal vitamin D level was 31.4% (90/287), which including the vitamin D deficiency was 13.9% (40/287). A total of 49.1% (141/287) people received nutritional vitamin D supplementation. The prevalence of IGRA positivity in this study was 25.1% (72/287). There was no significant difference in vitamin D concentrations or the proportion of vitamin D supplementation among the IGRA-positive and IGRA-negative groups (p = 0.789 and 0.496, respectively). In multivariate analysis, age >65 years old (odds ratio (OR), 1.89; 95% CI, 1.08–3.31; p = 0.026) and TB history (OR, 3.51; 95% CI, 1.38–8.91; p = 0.008) were independent predictors of IGRA positivity.ConclusionThis is the first study to report that vitamin D deficiency was not associated with IGRA positivity in a hemodialysis population. Aging and TB history were both independent predictors for LTBI.     

The co-expression characteristics of LAG3 and PD-1 on the T cells of patients with breast cancer reveal a new therapeutic strategy

Many studies have shown a special interaction between LAG3 and PD-1 in T cell inhibition, while the co-expression and effect of LAG3 and PD-1 on T cells in breast cancer patients are still not very clear. Here, with strict exclusion criteria, 88 patients with breast cancer and 18 healthy controls were enrolled. The percentages of LAG3⁺PD-1⁺ T cells in their peripheral blood (PBL) and tumor infiltrating T cells (TIL) were analyzed by flow cytometry, which showed an increase in TILs but no difference in PBLs and presented differences in TILs in different molecular subtypes (P < 0.05). In triple-negative breast cancer (TNBC), the highest percentages were observed, while in ER+/PR+ breast cancer, the lowest percentages were observed; however, these percentages were not different in different clinical stages (P > 0.05). Immunohistochemical staining showed that the expression of their ligands, PD-L1, MHC class II molecular and FGL1, was inconsistent in different molecular subtypes and clinical stages. Analysis of the functions of T cells with different phenotypes showed that the proliferation and secretion capacity of LAG3⁺PD-1⁺ T cells was obviously exhausted, with more than a two-fold of decrease compared with the groups of single positive LAG3 or PD-1 (P < 0.05). Finally, in a mouse model of TNBC, the dual blockade of LAG3 and PD-1 was indicated to achieve a better anti-tumour effect than either one alone (P < 0.05), which may provide a new strategy for the immunoregulatory treatment of patients with TNBC in the future.     

Differentiating between active and latent tuberculosis with chest computed tomography

PurposeThe purpose of this study was to evaluate the capabilities of chest computed tomography (CT) in distinguishing between active and latent tuberculosis in patients positive for interferon-gamma release assay (IGRA) testing, and to compare the performance of CT with that of quantitative IGRA testing in a low incidence setting.Materials and methodsPatients with latent or active tuberculosis define by an IGRA positive test were retrospectively recruited. Sensitivity, specificity and accuracy were determined for CT variables and quantitative IGRA results. Final diagnosis of active tuberculosis was based on clinical data and microbiological culture. Univariable and multivariable analyses were performed using logistic regression model to identify CT variables associated with the diagnosis of active tuberculosis.ResultsA total of 92 patients with positive IGRA results who underwent CT examination were included. There were 54 men and 38 women with a mean age of 53.5 ± 18 (SD) years (range: 40–68 years). Of them, 22 patients (24%) had positive Mycobacterium tuberculosis culture and 70 (76%) had latent tuberculosis. Among CT variables, consolidation had the greatest sensitivity (77%; 95%CI: 60–95%) and “tree-in-bud” the greatest specificity (97%; 95% CI: 93–100%) for the diagnosis of active tuberculosis. At univariable analysis “tree-in-bud”, splenic calcification and non-calcified lung nodules were the significant variables independently associated with active tuberculosis. At multivariable analysis, the adjusted odds ratio of “tree-in-bud” was 42.91 (95% CI: 5.62–327.42). Using an optimal threshold of 51 spots, quantitative IGRA yielded 64% sensitivity (95% CI: 44–84%) and 61% specificity (95% CI: 50–73%) for the diagnosis of active tuberculosis.ConclusionsIn a low incidence setting, chest CT, especially when “tree-in-bud” pattern is present, is superior to quantitative IGRA testing to identify patients with active tuberculosis among those with positive IGRA testing.     

受者特异性产生干扰素γ细胞与急性移植物抗宿主病的关系

目的研究异基因造血干细胞移植(allo-HSCT)中针对受者特异性产生干扰素γ细胞 (IFN-γ PC)与急性移植物抗宿主病(aGVHD)的关系。方法以37例HLA相合的同胞allo-HSCT患者为研究对象,将移植前供者、移植后患者外周血单个核细胞(PBMNC)分别作为反应细胞(RC),移植前受者PBMNC作为异基因刺激细胞(allo-SC),在混合淋巴细胞反应后用酶联免疫斑点法检测针对受者特异性IFN-γ PC,分析其与aGVHD的关系。结果 allo-HSCT前检测受者特异性IFN-γ PC水平, 移植后发生aGVHD组显著高于无aGVHD组(P<0．01);供者针对受者特异性IFN-γ Pc≥20／2×10~5 RC时,发生Ⅱ-Ⅳ度aGVHD的比例显著高于<20／2×10~5RC组(P<0．05)。aGVHD发生时患者针对移植前受者特异性IFN-γ PC水平显著高于移植前相应供者针对受者的水平(P<0．05);亦显著高于 aGVHD患者针对移植前供者的水平(P<0．01)。移植后14天(+14天)和+28天时,aGVHD组受者特异性IFN-γ PC水平均显著高于无aGVHD组(P值均<0．01)。aGVHD患者经过免疫抑制剂治疗7 d后,受者特异性IFN-γ PC较aGVHD发生时显著降低(P<0．05)。结论受者特异性IFN-γ PC的水平能够反映allo-HSCT前后的同种异体反应,有助于临床aGVHD的预测、诊断和监测。     

Assay of pleural fluid interleukin-6, tumour necrosis factor-alpha and interferon-gamma in the diagnosis and outcome correlation of tuberculous effusion

OBJECTIVE: To assess the usefulness of interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) in the diagnosis and prediction of outcome of pleural tuberculosis. PATIENTS AND METHODS: Pleural fluid from 32 TB and 34 non-TB patients was sent for assay of IL-6, TNF-alpha and IFN-gamma. Clinical parameters at presentation and residual pleural scarring at completion of treatment were assessed for pleural TB cases. RESULTS: The pleural fluid Levels of IL-6, TNF-alpha and IFN-gamma in TB patients were significantly higher than those with non-TB effusions (P values of <0.001, 0.018 and <0.001, respectively by independent t-test). Utility of these cytokines for diagnosis of pleural TB was evaluated using receiver operating characteristic (ROC) curve analysis. The cut-off values for IL-6, TNF-alpha and IFN-gamma determined in this analysis were 4000, 4 and 60 pg/ml respectively, and their sensitivity and specificity were 90.6% and 76.5%, 90.6% and 79.4%, 100% and 100%, respectively. The pretreatment pleural fluid IL-6 levels had a positive correlation with the number of febrile days after treatment (Pearson correlation test: r=0.60, P=0.009). A negative correlation was found between the percentage reduction in pleural fluid cytokines after 2 weeks treatment and the extent of residual pleural scarring (IL-6: r=-0.62, P=0.041; TNF-alpha: r=-0.65, P=0.030; IFN-gamma: r=0.83, P=0.002). CONCLUSION: Pleural fluid IL-6, TNF-alpha and IFN-gamma assays are useful in the diagnosis of pleural TB. The initial IL-6 level correlates with the number of febrile days. The percentage change of cytokines after 2 weeks of treatment also helps to predict residual pleural scarring.     

细胞因子IL-1β/ IFN-γ对骨骼肌成肌细胞基因表达的影响

目的研究细胞因子白细胞介素-1β(IL-1β)/干扰素-γ( IFN-γ)对鼠骨骼肌成肌细胞基因表达的影响.方法鼠骨骼肌成肌细胞在IL-1β/ IFN-γ混合液中孵育12 h,用抑制性削减杂交法克隆差异表达基因.随机挑取抑制性削减杂交所得克隆制备质粒,进行PCR扩增, 选取不同长度片断的产物,测序分析.结果发现1种骨骼肌结构蛋白基因(原肌球蛋白-4)表达下调,另发现2种凋亡相关的基因和2种功能不明基因的表达上调.结论①IL-1β/ IFN-γ下调骨骼肌结构蛋白基因,调节凋亡相关基因表达,推测可能是骨骼肌功能失调的原因之一;② 2种功能不明基因的表达为进一步研究骨骼肌功能失调的原因提供了新线索.     

瑞芬太尼对无痛人流患者的麻醉效果及IFN-γ、IL-10、NF-κB的变化研究

【目的】探讨瑞芬太尼对无痛人流患者的麻醉效果及干扰素-γ(IFN-γ)、白介素-10(IL-10)、核因子κB(NF-κB)变化的影响。【方法】于本院进行无痛人流患者140例,将其随机分为两组,观察组采用瑞芬太尼联合丙泊酚麻醉,对照组单纯采用丙泊酚麻醉。比较两组术中麻醉效果,术后苏醒时间以及对IFN-γ、IL-10、NF-κB水平的影响。【结果】观察组患者的优良率为98.6%(69/70),明显高于对照组的90.0%(63/70),且差异有显著性(P<0.05)。观察组患者术后苏醒时间及警觉/镇静(OAA/S)评分均优于对照组(P<0.05)。术后观察组患者IFN-γ水平明显低于对照组,IL-10、NF-κB水平明显高于对照组,且两组之间相比较差异均有显著性(P<0.05)。【结论】瑞芬太尼对无痛人流患者的麻醉效果好,可以有效降低患者血清内IFN-γ水平,提高IL-10、NF-κB水平,患者术后苏醒时间缩短,有利于患者术后恢复。     

结核病患者外周血γ干扰素释放试验假阴性的相关因素分析

目的 分析影响结核病患者外周血γ干扰素释放试验(interferon-gamma release assay,IGRA)检测假阴性的影响因素。方法 回顾性分析2018年1月至2020年3月解放军总医院第八医学中心结核四科收治的资料完整、外周血IGRA检测阴性和阳性的结核病患者,分别作为IGRA假阴性组(38例)和IGRA阳性组(119例),收集其一般情况、病史特点、血清生化指标和外周血淋巴细胞亚群,采用单因素和多因素logistic回归分析导致IGRA检测结果假阴性的影响因素。结果 IGRA假阴性组淋巴细胞计数、T细胞计数、CD4⁺T细胞计数、CD8⁺T细胞计数、NKT细胞计数M(Q₁,Q₃)分别为1.15(0.77,1.58)×10⁹个/L、867.50(508.75,1135.50)个/μl、493.00(256.00,673.75)个/μl、254.50(170.25,429.25)个/μl、38.50(16.50,88.25)个/μl,均明显低于IGRA阳性组[分别为1.46(0.99,1.88)×10⁹个/L、1013.00(667.00,1394.00)个/μl、590.00(386.00,850.00)个/μl、335.00(232.00,561.00)个/μl、57.00(30.00,121.00)个/μl,差异均有统计学意义(Z值分别为-2.512、-2.143、-2.092、-2.303、-2.338,P值分别为0.012、0.032、0.036、0.021、0.019)。logistic回归分析结果显示,NKT细胞计数低于正常值(<40个/μl)的患者,IGRA检测出现假阴性的风险是NKT细胞计数正常者的2.440倍(95%CI:1.159~5.134)。结论 NKT细胞计数的减少可能导致外周血IGRA出现假阴性。