Detection of immunological biomarkers correlated with asthma control and quality of life measurements in sera from chronic asthmatic patients
Clinical outcomes of patients with asthma are highly variable. Immunological biomarkers associated with asthma control have not been elucidated. To identify the association between clinical control of asthma and serum immunological profiles of asthmatics and compare these profiles with those of healthy controls by using a multiplex assay. Sera were obtained from 28 nonsmokers 18 to 55 years of age with moderate and severe persistent asthma. Patients were classified as having well-controlled (WC, n = 14) or poorly controlled (PC, n = 14) asthma based on their responses to the Asthma Control Questionnaire and Asthma Quality of Life Questionnaire. Sera from nonasthmatic control individuals (NAC, n = 14) were used for comparison. Levels of 50 analytes, including cytokines, chemokines, angiogenic, and growth factors, were determined, using a multiplex assay. Twelve of the 29 cytokines levels were significantly higher in patients with asthma than in NACs, but only interferon gamma levels were significantly lower in patients with asthma than in the NAC group. Among these, interleukin (IL)-3 and IL-18 levels were significantly higher in the PC group than the WC group. Five of the 12 tested chemokine levels were significantly higher in patients with asthma than in NACs. Five of six growth factor levels were significantly higher in patients with asthma than in NACs, and 3 were higher in PC than WC. Interleukin-18, fibroblast growth factor, hepatocyte growth factor, and stem cell growth factor-beta were positively correlated with poor asthma control and negatively with quality of life scores. Increased serum levels of fibroblast growth factor, hepatocyte growth factor, and stem cell growth factor-beta might be useful biomarkers of asthma control status and targets of future asthma therapy.
[Show abstract] [Hide abstract] ABSTRACT: Asthma is a chronic inflammatory disease of the airways, resulting in bronchial hyperresponsiveness with every allergen exposure. It is now clear that asthma is not a single disease, but rather a multifaceted syndrome that results from a variety of biologic mechanisms. Asthma is further problematic given that the disease consists of many variants, each with its own etiologic and pathophysiologic factors, including different cellular responses and inflammatory phenotypes. These facets make the rapid and accurate diagnosis (not to mention treatments) of asthma extremely difficult. Protein biomarkers can serve as powerful detection tools in both clinical and basic research applications. Recent endeavors from biomedical researchers have developed technical platforms, such as cytokine antibody arrays, that have been employed and used to further the global analysis of asthma biomarker studies. In this review, we discuss potential asthma biomarkers involved in the pathophysiologic process and eventual pathogenesis of asthma, how these biomarkers are being utilized, and how further testing methods might help improve the diagnosis and treatment strain that current asthma patients suffer.
- "Using a 50-target protein multiplex array which included detection of cytokines, chemokines, and growth factors, this group found that several proteins could serve as potential disease biomarkers (notably, FGF, HGF, and SCGFí µí»½) for the moderate and severe asthma groups. Furthermore, these same biomarkers in addition to IL-18 were found to positively correlate with poor asthmatic control and were associated negatively with quality of life scores . With the hopes of identifying critically important inflammatory molecules in COPD and asthma, Kim et al. analyzed asthma sputum samples with a 79 target multiplex array. "
[Show abstract] [Hide abstract] ABSTRACT: All of life is regulated by complex and organized chemical reactions that help dictate when to grow, to move, to reproduce, and to die. When these processes go awry, or are interrupted by pathological agents, diseases such as cancer, autoimmunity, or infections can result. Cytokines, chemokines, growth factors, adipokines, and other chemical moieties make up a vast subset of these chemical reactions that are altered in disease states, and monitoring changes in these molecules could provide for the identification of disease biomarkers. From the first identification of carcinoembryonic antigen, to the discovery of prostate-specific antigen, to numerous others described within, biomarkers of disease are detectable in a plethora of sample types. The growing number of biomarkers for infection, autoimmunity, and cancer allow for increasingly early detection, to identification of novel drug targets, to prognostic indicators of disease outcome. However, more and more studies are finding that a single cytokine or growth factor is insufficient as a true disease biomarker and that a more global perspective is needed to understand true disease biology. Such a broad view requires a multiplexed platform for chemical detection, and antibody arrays meet and exceed this need by performing this detection in a high-throughput fashion. Herein, we will discuss how antibody arrays have evolved, and how they have helped direct new drug target design, helped identify therapeutic disease markers, and helped in earlier disease detection. From asthma to renal disease, and neurological dysfunction to immunologic disorders, antibody arrays afford a bright future for new biomarker discovery.
- "Histamine release in turn triggers the rise of intracellular calcium , muscle contraction, and airway narrowing, hallmark symptoms of asthma. Currently, there is no single serological biomarker used in routine clinical asthma diagnosis and prognosis, though as described previously, several researchers are making quick progress [67,68]. Antibody arrays have also been used in the study of cell-mediated type IV hypersensitivities such as graft versus host disease (GVHD). "
[Show abstract] [Hide abstract] ABSTRACT: Human airways contact with pathogen-associated molecular patterns and danger-associated molecular patterns present in many environments. Asthmatic's airways may be more susceptible to these patterns and lead to inflammasome activation; however, the participation of inflammasome in the development and exacerbation of asthma is not fully understood and remains controversial. Asthma is a heterogeneous group composed of different airway inflammation patterns with different underlying immune mechanisms. One mechanism is neutrophilic airway inflammation based on the axis of inflammasome activation, interleukin (IL) 1β/IL-18 production, T helper 17 activation, IL-8/IL-6 overproduction, and neutrophilic inflammation. The role of inflammasome activation has been highlighted in experimental asthma models and some evidence of inflammasome activation has been recently demonstrated in human neutrophilic asthmatic airways. In addition to caspase-1 activation, proteinase 3 and other protease from activated neutrophils directly cleave pro-IL-1β and pro-IL-18 to IL-1β and IL-18, which contribute to the phenotype of subsequent adaptive immune responses without inflammasome activation. Data suggests that neutrophilics in asthmatic airways may have an additional effect in initiating inflammasome activation and amplifying immune responses. Among the mediators from neutrophils, S100A9 seems to be one candidate mediator to explain the action of neutrophils in amplifying the airway inflammation in concert with inflammasome.
- "IL-1β is increased in the serum and bronchoalveolar lavage fluids of human asthmatics and decreases after steroid inhalation101112. IL-18 levels are increased in theperipheral blood of asthmatics; however, controversial results have been reported131415. The data suggest a possible presence of inflammasome activation in the asthmatic airways. "