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Th2 biomarkers

Annalisa Ciabattini, Elena Pettini, Fabio Fiorino, Gabiria Pastore, Peter Andersen, Gianni Pozzi, Donata Medaglini
Adjuvants contribute to enhancing and shaping the vaccine immune response through different modes of action. Here early biomarkers of adjuvanticity after primary immunization were investigated using four different adjuvants combined with the chimeric tuberculosis vaccine antigen H56. C57BL/6 mice were immunized by the subcutaneous route with different vaccine formulations, and the modulation of primary CD4(+) T cell and B cell responses was assessed within draining lymph nodes, blood, and spleen, 7 and 12 days after priming...
2016: Frontiers in Immunology
Nicolette M Jeanblanc, Philip M Hemken, Maria J Datwyler, Susan E Brophy, T Scott Manetz, Rozanne Lee, Meina Liang, Partha S Chowdhury, Reena Varkey, Ethan P Grant, Katie Streicher, Lydia Greenlees, Koustubh Ranade, Gerard J Davis
BACKGROUND: Periostin is being investigated as a potential biomarker for T-helper-2 (Th2)-driven asthma or eosinophilic inflammation and may help to identify patients more likely to benefit from interleukin-13-targeted treatments. We report the development and analytic performance of the investigational use only Architect Periostin Immunoassay, a new automated assay developed to detect serum periostin concentrations. METHODS: We assessed assay performance in terms of precision, sensitivity, linearity, interference from classical immunoassay interferents and representatives of common asthma medications, specimen handling, and isoform reactivity...
October 14, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
Tao Huang, Meredith Hazen, Yonglei Shang, Meijuan Zhou, Xiumin Wu, Donghong Yan, Zhonghua Lin, Margaret Solon, Elizabeth Luis, Hai Ngu, Yongchang Shi, Arna Katewa, David F Choy, Nandhini Ramamoorthi, Erick R Castellanos, Mercedesz Balazs, Min Xu, Wyne P Lee, Marissa L Matsumoto, Jian Payandeh, Joseph R Arron, Jo-Anne Hongo, Jianyong Wang, Isidro Hötzel, Cary D Austin, Karin Reif
Eosinophilic inflammation and Th2 cytokine production are central to the pathogenesis of asthma. Agents that target either eosinophils or single Th2 cytokines have shown benefits in subsets of biomarker-positive patients. More broadly effective treatment or disease-modifying effects may be achieved by eliminating more than one inflammatory stimulator. Here we present a strategy to concomitantly deplete Th2 T cells, eosinophils, basophils, and type-2 innate lymphoid cells (ILC2s) by generating monoclonal antibodies with enhanced effector function (19A2) that target CRTh2 present on all 4 cell types...
May 19, 2016: JCI Insight
Anna Winberg, Olga Nagaeva, Ivan Nagaev, Catarina Lundell, Ignacio Arencibia, Lucia Mincheva-Nilsson, Eva Rönmark, Christina E West
BACKGROUND: There is need for prognostic markers for symptomatic food allergy since current diagnostic methods are insufficient and/or time and labor consuming. OBJECTIVE: To estimate the cytokine mRNA profiles in peripheral blood mononuclear cells (PBMC) before and after a double-blind placebo-controlled food challenge series in schoolchildren with suspected allergy to milk, egg or cod and in healthy controls. Analyses of fecal inflammatory biomarkers before and after the challenge were included...
December 2016: Cytokine
Majid Gharghani, Shima Dokoohaki, Amir Ghanbari, Naser Farhadi, Kazem Zibara, Saeid Khodadoust, Mohammad Parishani, Mehdi Ghavami Zadeh, Heibatollah Sadeghi
Melatonin has a beneficial role in adult rat models of multiple sclerosis (MS). In this study, melatonin treatment (10 mg/kg/d) was investigated in young age (5-6 weeks old) Lewis rat model of acute experimental autoimmune encephalomyelitis (EAE) followed by assessing serum levels of lactate and melatonin. Results showed that clinical outcomes were exacerbated in melatonin- (neurological score=6) versus PBS-treated EAE rats (score=5). Melatonin caused a significant increase in serum IFN-γ, in comparison to PBS-treated EAE rats whereas no considerable change in IL-4 levels were found, although they were significantly lower than those of controls...
October 3, 2016: Clinical and Experimental Pharmacology & Physiology
Jasper H Kappen, Stephen R Durham, Hans In 't Veen, Mohamed H Shamji
Clinical and immunologic tolerance are hallmarks of successful allergen immunotherapy (AIT). Clinical benefits such as reduced symptoms, pharmacotherapy intake and improvement of quality of life persist following cessation of treatment. Successful AIT is associated with suppression of allergic inflammatory cells such as mast cells, eosinophils and basophils in target organs. Furthermore, AIT down-regulates type 2 innate lymphoid cells and allergen-specific type 2 T-helper (Th2) cells. The immunologic tolerant state following AIT is associated with the induction of distinct phenotypes of regulatory T-cells (T-regs) including interleukin (IL)-10-, IL-35- and transforming growth factor (TGF)-β- producing T-regs and FoxP3(+) T-regs...
September 27, 2016: Therapeutic Advances in Respiratory Disease
Sardar Sindhu, Nadeem Akhter, Steve Shenouda, Ajit Wilson, Rasheed Ahmad
BACKGROUND: Fetuin-A/AHSH is a novel hepatokine that acts as a vascular calcification inhibitor and as an endogenous TLR-4 ligand. Fetuin-A may act as a positive or negative acute phase protein (APP) in disease conditions. The relationship between circulatory fetuin-A and inflammatory biomarkers in type-2 diabetes (T2D) remains controversial. Therefore, the purpose of this study was to determine the plasma fetuin-A levels in 53 T2D (BMI = 29.7 ± 4.5 kg/m(2)) and 72 non-diabetic individuals (BMI = 28...
September 26, 2016: BMC Immunology
Hitokazu Esaki, Patrick M Brunner, Yael Renert-Yuval, Tali Czarnowicki, Thy Huynh, Gary Tran, Sarah Lyon, Giselle Rodriguez, Supriya Immaneni, Donald B Johnson, Bruce Bauer, Judilyn Fuentes-Duculan, Xiuzhong Zheng, Xiangyu Peng, Yeriel D Estrada, Hui Xu, Christina de Guzman Strong, Mayte Suárez-Fariñas, James G Krueger, Amy S Paller, Emma Guttman-Yassky
BACKGROUND: Atopic dermatitis (AD) affects 15% to 25% of children and 4% to 7% of adults. Paradigm-shifting discoveries about AD have been based on adult biomarkers, reflecting decades of disease activity, although 85% of cases begin by 5 years. Blood phenotyping shows only TH2 skewing in patients with early-onset pediatric AD, but alterations in early pediatric skin lesions are unknown, limiting advancement of targeted therapies. OBJECTIVE: We sought to characterize the early pediatric AD skin phenotype and its differences from pediatric control subjects and adults with AD...
September 15, 2016: Journal of Allergy and Clinical Immunology
Diego Bagnasco, Matteo Ferrando, Gilda Varricchi, Giovanni Passalacqua, Giorgio Walter Canonica
Asthma is a high-prevalence disease, still accounting for mortality and high direct and indirect costs. It is now recognized that, despite the implementation of guidelines, a large proportion of cases remain not controlled. Certainly, adherence to therapy and the education of patients remain the primary objective, but the increasingly detailed knowledge about the pathogenic mechanisms and new biotechnologies offer the opportunity to better address and treat the disease. Interleukin (IL)-13 and IL-4 appear as the most suitable targets to treat the T helper 2 (TH2)-mediated forms (endotypes) of asthma...
2016: International Archives of Allergy and Immunology
Hern-Tze Tina Tan, Kazunari Sugita, Cezmi A Akdis
PURPOSE OF REVIEW: The development of biological therapies has rapidly progressed during the last few years, and major advances were reported for the treatment of allergic diseases, such as atopic dermatitis, allergic rhinitis, urticaria, food allergy, and asthma. Here, we review biologicals targeting the type 2 immune response involving Th2 cells, type 2 innate lymphoid cells, natural killer T cells, mast cells, basophils, and epithelial cells, such as IL-4, IL-5, IL-13, IL-31, tumor necrosis factor alpha (TNF-α), and thymic stromal lymphopoietin (TSLP)...
October 2016: Current Allergy and Asthma Reports
Jeffrey R Stokes, Thomas B Casale
OBJECTIVE: To describe the concept of precision medicine in treating severe asthma and the utility of relevant biomarkers. DATA SOURCES: PubMed was searched for published articles on human clinical trials using biologics for T-helper type 2 cell (TH2)-low and TH2-high asthma. STUDY SELECTIONS: Studies were selected if they were double-masked, randomized, placebo-controlled trials published in peer-reviewed journals and relevant to the topic...
August 2016: Annals of Allergy, Asthma & Immunology
Huihui You, Rui Li, Chenxi Wei, Shaohui Chen, Lin Mao, Zhenye Zhang, Xu Yang
Di-(2-ethylhexyl) phthalate (DEHP), a commonly used plasticizer, has an adjuvant effect in combination with ovalbumin (OVA). The adjuvant effect of DEHP has already been verified in our previous studies. In this study, to further investigate whether thymic stromal lymphopoietin (TSLP) was involved in the DEHP-adjuvant effect, DEHP was administered through a daily gavage exposure route. Mice were sensitized with ovalbumin (OVA) to trigger allergic responses, and an anti-TSLP monoclonal antibody was used to neutralize the effect of TSLP...
2016: PloS One
Garry M Walsh
INTRODUCTION: The development of monoclonal antibody-based biologics targeted at inhibition of the Th2 cytokines IL-4, IL-5 and IL-13 represent potentially effective treatments for patients with the glucocorticoid refractory eosinophilic asthma phenotype. AREAS COVERED: Asthma exhibits marked heterogeneity both clinically and at the molecular phenotypic level, requiring specifically targeted treatments to block the key pathways of the disease. It is becoming apparent that significant clinical effects with anti-cytokine-based biologic therapies are more likely in carefully selected patient populations that take asthma phenotypes into account...
August 2, 2016: Expert Review of Clinical Immunology
R M Valenzuela, M Kaufman, K E Balashov, K Ito, S Buyske, S Dhib-Jalbut
A prospective study of 62 patients with relapsing-remitting multiple sclerosis (RRMS) treated with Glatiramer acetate (GA) was conducted to evaluate the value of baseline and treatment-modulated cytokines in predicting the clinical response to the drug after 2years of therapy. There were 32 responders and 30 non-responders. GA upregulated Th2/regulatory cytokines and inhibited Th1 cytokines in sera or PBMC supernatants 3 and 6months into treatment. We found two prognostic models with clinical utility. A model based on IL-18 at baseline, the change in TNFa from baseline to 3months, the change in IL-4 from baseline to 6months, and the change in the log of the ratio of TNFa/IL-4 from baseline to 6months had an area under the curve (AUC) of 0...
July 2, 2016: Journal of Neuroimmunology
Srirama Krupanidhi
The mammalian conceptus is a semi-allograft. The maternal tolerance towards semi-allograft is primed by a battery of cytokines and resident decidual cells. Invasion of embryonic trophoblast, decidual vascular remodeling and unresponsive incipient 'Triple-negative' (CD3-, CD4- and CD8-) T-cells of foetus promote normal pregnancy. On the other hand, the maternal cytokine profile shift towards Th1 response is shown to enhance the risk during pregnancy. The periodical examination of maternal serum levels of Th1 and Th2 response mediated cytokines constitutes prognostic biomarkers to initiate therapeutic regimens...
July 2015: Roumanian Archives of Microbiology and Immunology
Tinne C J Mertens, Pieter S Hiemstra, Christian Taube
The T helper 2 (Th2) cytokine interleukin(IL)-13 is a central regulator in goblet cell metaplasia and induces the recently described Th2 gene signature consisting of periostin (POSTN), chloride channel regulator 1 (CLCA1) and serpin B2 (SERPINB2) in airway epithelial cells. This Th2 gene signature has been proposed as a biomarker to classify asthma into Th2-high and Th2-low phenotypes. Clinical studies have shown that the macrolide antibiotic azithromycin reduced clinical symptoms in neutrophilic asthma, but not in the classical Th2-mediated asthma despite the ability of azithromycin to reduce IL-13-induced mucus production...
August 2016: Pulmonary Pharmacology & Therapeutics
J N Gajiyev, E G Tagiyev, N J Gadjiyev
The results of surgical treatment of 137 patients, suffering obturation jaundice of non-tumoral etiology, were analyzed. In all the patients the cause of obturation jaundice was choledocholithiasis. Roncoleukin was infused intravenously additionally in a complex of therapy. A degree of hepatic dysfunction was determined, taking into account the cholestasis markers. In 23 patients purulent cholangitis have occurred on background of obturation jaundice. Concentration of cytokins TNF-α, IFN-γ, IL-1, IL-2, IL-4, IL-6, IL-10 in sera were determined, using immunoassay analysis...
February 2016: Klinichna Khirurhiia
Julia Kzhyshkowska, Alexandru Gudima, Kondaiah Moganti, Alexei Gratchev, Alexander Orekhov
Low-grade chronic inflammation underlies the development of the most dangerous cardiometabolic disorders including type 2 diabetes and its vascular complications. In contrast to acute inflammation induced by bacteria and viruses, chronic inflammation can be driven by abnormal reaction to endogenous factors, including Th2 cytokines, metabolic factors like advanced glycation end products (AGEs), modified lipoproteins, or hyperglycemia. The key innate immune cells that recognize these factors in blood circulation are monocytes...
March 2016: Transfusion Medicine and Hemotherapy
K Torres-Poveda, A I Burguete-García, M Bahena-Román, R Méndez-Martínez, M A Zurita-Díaz, G López-Estrada, K Delgado-Romero, O Peralta-Zaragoza, V H Bermúdez-Morales, D Cantú, A García-Carrancá, V Madrid-Marina
BACKGROUND: Alterations in the host cellular immune response allow persistent infections with High-Risk Human Papillomavirus (HR-HPV) and development of premalignant cervical lesions and cervical cancer (CC). Variations of immunosuppressive cytokine levels in cervix are associated with the natural history of CC. To assess the potential role of genetic host immunity and cytokines serum levels in the risk of developing CC, we conducted a case-control study paired by age. METHODS: Peripheral blood samples from patients with CC (n = 200) and hospital controls (n = 200), were used to evaluate nine biallelic SNPs of six cytokine genes of the adaptive immune system by allelic discrimination and cytokines serum levels by ELISA...
2016: BMC Cancer
Andrea Fava, Raffaello Cimbro, Fredrick M Wigley, Qing-Rong Liu, Antony Rosen, Francesco Boin
BACKGROUND: Scleroderma is an antigen-driven T cell-mediated autoimmune disease. Presence of anti-topoisomerase-I antibodies is associated with pulmonary fibrosis and predicts increased mortality. Characterization of autoreactive T lymphocytes may shed light on disease pathogenesis and serve as a biomarker for disease activity. Here, we aimed to quantify and functionally characterize circulating topoisomerase I (topo-I)-specific CD4+ T cells and to define their association with presence and progression of interstitial lung disease (ILD) in patients with scleroderma...
2016: Arthritis Research & Therapy
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