Biomarkers on patient T cells diagnose active tuberculosis and monitor treatment response

BACKGROUND. The identification and treatment of individuals with tuberculosis (TB) is a global public health priority. Accurate diagnosis of pulmonary active TB (ATB) disease remains challenging and relies on extensive medical evaluation and detection of Mycobacterium tuberculosis (Mtb) in the patient’s sputum. Further, the response to treatment is monitored by sputum culture conversion, which takes several weeks for results. Here, we sought to identify blood-based host biomarkers associated with ATB and hypothesized that immune activation markers on Mtb-specific CD4⁺ T cells would be associated with Mtb load in vivo and could thus provide a gauge of Mtb infection.METHODS. Using polychromatic flow cytometry, we evaluated the expression of immune activation markers on Mtb-specific CD4⁺ T cells from individuals with asymptomatic latent Mtb infection (LTBI) and ATB as well as from ATB patients undergoing anti-TB treatment.RESULTS. Frequencies of Mtb-specific IFN-γ⁺CD4⁺ T cells that expressed immune activation markers CD38 and HLA-DR as well as intracellular proliferation marker Ki-67 were substantially higher in subjects with ATB compared with those with LTBI. These markers accurately classified ATB and LTBI status, with cutoff values of 18%, 60%, and 5% for CD38⁺IFN-γ⁺, HLA-DR⁺IFN-γ⁺, and Ki-67⁺IFN-γ⁺, respectively, with 100% specificity and greater than 96% sensitivity. These markers also distinguished individuals with untreated ATB from those who had successfully completed anti-TB treatment and correlated with decreasing mycobacterial loads during treatment.CONCLUSION. We have identified host blood-based biomarkers on Mtb-specific CD4⁺ T cells that discriminate between ATB and LTBI and provide a set of tools for monitoring treatment response and cure.TRIAL REGISTRATION. Registration is not required for observational studies.FUNDING. This study was funded by Emory University, the NIH, and the Yerkes National Primate Center.     

Enzyme-Assisted Extraction of Narirutin from Citri Reticulatae Pericarpium and Anti-allergic Asthma Activity

Background: Asthma is a heterogeneous disorder of the airways related to inflammation; it affects millions of people worldwide. Due to the side effects of inhaled corticosteroids, researchers focused on the therapeutic effects of compounds derived from natural products. Objective: To investigate the therapeutic benefits of Narirutin a valuable flavonoid in Citri Reticulatae Pericarpium for asthma. Methods: Narirutin was extracted using the enzyme-assisted method with the L9 (34) orthogonal array to optimize the temperatures, pH, and reaction time. The mechanism of action of Narirutin was investigated via ELISA, flow cytometry, and Western blot analysis in vivo. Results: Narirutin suppressed inflammatory cell infiltration in the lung tissue and decreased IgE and IgG1 levels in serum in vivo. It can also alleviate interleukin (IL)-4, IL-5, and interferon-γ concentrations in bronchoalveolar lavage fluid in mice. Moreover, it increased the ratio of CD4+/CD8+ T cells. Additionally, Narirutin significantly suppressed p-ERK1/2 and p-JNK expression in the MAPK signaling pathway. Conclusion: Narirutin affects the Th1/Th2 imbalance through the p-ERK and p-JNK suppression in the MAPK signaling pathway.     

肝移植后供肝和宿主免疫学状态的变化

目的观察供肝免疫原性和宿主对供体抗原反应能力的动态改变。方法利用近交系LEW到WF的大鼠肝移植自发免疫耐受模型,取出不同时期的供肝,分别刺激长期生存的WF宿主,观察能否诱导出肝损害；另外对LEW→WF肝移植后不同时期的宿主,再次给予供体抗原刺激。结果(1)移植后第1、2天的同种移植肝,可激起长期生存的宿主出现暂时性肝损害(121±33、83±21),但第3天以后的则不能(28±9)。(2)给予供体同源的脾细胞刺激后,移植后7、14、28 d的宿主均未能诱导肝损害(56±17、66±11、61±35),但第56、84或112天的宿主均可被诱导出暂时性肝损害(98±25、158±43、330±82)。结论(1)肝移植后供肝的免疫原性在术后3 d基本消失。(2)移植术后1个月内宿主对供体抗原的刺激是处于低(无)反应状态的。     

氦氖激光照射小白鼠对免疫功能的影响

采用两种不同功率的He—Ne激光分别照射小白鼠胸腺区、脾区及腹部,观察体液免疫、细胞免疫及腹腔巨噬细胞吞噬功能。结果表明激光照射组与对照组有显著差异(P<001),故证明激光有免疫调节剂的作用。为激光的临床治疗提供了可靠的理论依据。     

Immunology

A selection of interesting papers that were published in the two months before our press date in major journals most likely to report significant results in immunology.     

小牛胸腺肽治疗乙型肝炎的疗效研究

本文报告了小牛胸腺肽(CTP)治疗乙肝患者50例(慢迁肝23例,慢活肝16例,重症肝炎11例)和HBsAg携带者10例的结果,CTP对消除或减轻临床症状和体征,改善肝功能具有明显的疗效,对慢迁肝,慢活肝和重症肝炎的治疗效果基本相同,各组间无显著性差异。对HBV血清学指标无重要改变,对HBsAg携带者疗效不侍。并对剂景、疗程与疗效的关系进行了讨论。     

原发性肝癌HBV感染模式与AFP水平相关性研究

目的:探讨原发性肝癌(PHC)患者乙肝病毒(HBV)感染模式与血清甲胎蛋白(AFP)水平的关系。方法:应用酶免疫检测法(ELISA)、聚合酶链反应(PCR)及放射免疫技术分别测定100例原发性肝癌患者血清乙型肝炎病毒指标(HBV-M)及AFP。结果:100例PHC患者中,HBV-M阳性88例(88％),阴性12例(12％),HBV-M阳性者AFP水平高于阴性者147 ng/mL,二者有非常显著性意义(P<0.01),且HBV-M阳性者AFP升高(68.4％)的比例明显高于HBV-DNA阴性者(31.6％)(P<0.01)。PHC患者HBV感染模式分析中,HBsAg、HBeAb、HBcAb阳性和HBV-DNA阳性最多,为56例(63.6％),其次为HBsAg、HBeAg、HBcAb和HBV-DNA阳性,为9例(10.2％)。结论:HBV是原发性肝癌发生的重要原因,在PHC患者中,AFP升高与HBV感染、复制相关。     

Allergic bronchopulmonary aspergillosis: Reactivity of IgE and IgG antibodies with antigenic components of Aspergillus fumigatus (IgE/IgG antigen complexes)

Sera of patients with ABPA were tested by XRIE tests incorporating their own serum (self-XRIE) to detect the presence of IgG/IgE antigen complexes to a “reference” Aspergillus fumigatus preparation. Of the 32 sera studied, 29 (90%) had visible precipitin (IgG) peaks, and 27 of these 29 as well as the three apparently precipitin-negative sera, i.e., 30 (94%), showed binding of specific IgE by autoradiography. The two precipitin-positive sera that did not show IgE binding were also skin test negative and RAST negative to this A. fumigatus antigen. Specific IgG as determined in ELISA correlated well with the grading of the XIE precipitin peaks (p < 0.05). There was also a highly significant correlation between specific IgE by RAST and grading the radioactive uptake seen in the autoradiograph (p < 0.001) indicating, for each serum, the presence of IgG antibodies to most of the components to which there was specific IgE. In the self-XRIE tests there was considerable variation of reactivity from serum to serum, in numbers of antigen/antibody peaks observed, in relative peak heights, and in the intensity of the respective staining. By comparing each test to a “reference” pattern developed with the use of an ABPA serum pool, the antigenic components of A. fumigatus were found to be of two main types: (1) antigens that appeared to be poorly precipitating (possibly low-molecular-weight components) but showed strong IgE binding (these were apparently major allergenic components and with one exception proved to be the faster migrating components) and (2) antigens that produced the strongest precipitin reactions with only weak binding of specific IgE and therefore minor allergenic components.     

Engulfment of mast cell secretory granules on skin inflammation boosts dendritic cell migration and priming efficiency

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Ras homolog gene family H (RhoH) deficiency induces psoriasis-like chronic dermatitis by promoting TH17 cell polarization

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