Browsing by Author "Antunes, Marilia"
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- Association between the adrenoreceptor β2 gene and pediatric asthma severity – a study of the PACMAN cohortPublication . Caleiro, Maria Leonor; Soares, Patricia; Antunes, Marilia"Pharmacogenetics of Asthma medication in Children: Medication with Anti-Inflammatory effects" (PACMAN) is an observational retrospective pharmacy-based study carried out in 2009, in the Netherlands, aiming to investigate the effects of genetic variation on treatment response to asthma medication in children and to identify (profiles of) SNPs that characterize response phenotypes. Data on respiratory symptoms and medication use, including medication type and amount, was collected from pharmaceutical records of asthmatic children and data on the children’s sex, age, genetic traits, and ethnicity. We aimed to assess the association between asthma severity and the Arg16Glu polymorphism of the β2 adrenoreceptor gene (ADRB2). This gene is expressed in bronchial muscle cells, which is involved in the physiological response of the airway response and has been associated with clinical drug response and asthma exacerbations. We used the PACMAN data and considered the dispensing of oral corticosteroid prescriptions as a proxy of the disease severity since corticoids are commonly used in uncontrolled asthmatic states (exacerbations). We considered two different genetic models – additive and genotypic, which can be translated for analysis purposes into a numeric format, corresponding to the number of copies of the minor allele, and categorical (each genotype representing a category), respectively. We used models of the class of the Generalized Linear Mixed Models for count data with excess of zeros, namely zero-inflated and hurdle models, considering a Negative Binomial distribution to account for overdispersion. Both models included the polymorphism in the zero and count components and were adjusted for children’s baseline characteristics. In both approaches to deal with the excess of zeros, a significant effect of the polymorphism was found only in the binary component of the models. In the count component, only sex and age showed a significant effect. This points towards the existence of an effect of the polymorphism in the presence of asthma exacerbations, with not shown effect in the frequency of OCS prescription.
- Investigating the impact of COVID-19 vaccines on the red blood cell immune function by omics-based approachesPublication . Saraiva, Joana; Coelho, Cristina Valentim; Vaz, Fátima; Antunes, Marilia; Neves, Sofia; Ricardo, Peliano; Andrade, Odília; Miranda, Armandina; Melo, Aryse; Roque, Carla; Guiomar, Raquel; Mohammad, Hamza; Soares, Nelson; Penque, DeborahThe role of red blood cells (RBC) in the immune system is increasingly recognized. However, RBC-derived molecules with an immunomodulatory role in health and disease, as well as in vaccine immunogenicity are still poorly investigated. Taking as a model the emergent COVID-19 vaccines, we aimed to investigate whether vaccines induce proteome and/or metabolome changes in RBCs able to affect T-cell immune activity, as a mechanistic test for vaccine immunization regulated by RBCs. Our ultimate goal is to identify RBC immunomodulators as potential co-adjuvants in the formulation of next-generation vaccines with bolstered efficacy and duration. A biobank of blood samples collected longitudinally under ‘omics’ quality control from subjects (n=39) that underwent vaccination for COVID-19 between April and September 2021 was created. This biobank is associated with extensive clinical data, including demographic data, COVID-19 PCR diagnosis, hematological and vaccine effectivity data. Linear Mixed Models, were used to evaluate the association between biometrical characteristics, health related habits, vaccine technology and vaccine effectivity and hematological parameters, along the different time-points (t0-t4) under study, i.e, before and after (24-72h or 30 days) of the first and second dose of vaccine. Statistical analyses were performed using R software version 4.1.2. Results showed significant differences (p<0.05) before/after vaccination in a set of hematological variables (e.g., hemoglobin, lymphocytes and monocytes values), as well in terms of vaccine effectivity and vaccine technology (mRNA or adenovirus – based vaccines). Preliminary data from proteomics and metabolomics analysis of RBCs along the different time-points (t0-4) of immunization response will be also presented and discussed. The knowledge gained with this project can generate important evidence-based recommendations intended to optimize vaccine immunization, by recognizing the impact of blood cells such RBCs in the immune system regulation.
- Proteoforms of transthyretin - candidate biomarkers in diagnosis of obstructive sleepPublication . Torres, VM; Feliciano, Amélia; Antunes, Marilia; Vaz, Fatima; Penque, DeborahObstructive sleep apnea (OSA) is a common sleep-related breathing disorder which is characterized by recurrent occurrence of partial or complete closure of the upper airway during sleep, despite ongoing efforts to breathe. The majority of patients with OSA remain undiagnosed since most of them only come to the attention of a clinician when they complain of daytime sleepiness or when their bed partners report loud snoring or witnessed apnea episodes.Epidemiological studies have indicated that OSA affects 6–13% of the adult population. OSA is multifactorial disease, also considered as metabolic syndrome, which diagnosis in early stages is challenging thus often remain undiagnosed. Recently was found connection between transthyretin (TTR) protein modifications present in human plasma samples and appearance of sleep apnea syndrome1,2 . Mass Spectrometric Immunoassay (MSIA) was successfully applied previously on identification of and quantification of TTR variants present in human serum3. We took advantage on this powerful method to investigate possible modifications of TTR proteoforms in patients with OSAS.