Fernando Marques-Garcia, Ph.D., David Hansoe Heredero Jung, M.D., and Sandra Elena Pérez, B.D.. Ann Lab Med 2022;42:169-77. https://doi.org/10.3343/alm.2022.42.2.169

Background: Asthma is a heterogeneous syndrome with a broad clinical spectrum and high drug response variability. The inflammatory response in asthma involves multiple effector cells and mediator molecules. Based on asthma immunopathogenesis, precision medicine can be a promising strategy for identifying biomarkers. Biologic therapies acting on the IL-5/IL-5 receptor axis have been developed. IL-5 promotes proliferation, differentiation and activation of eosinophils by binding to the IL-5 receptor, located on the surface of eosinophils and basophils. This study aimed to investigate the expression of IL5RA in patients with several types of asthma and its expression after treatment with benralizumab, a biologic directed against IL-5 receptor subunit alpha.Methods: Sixty peripheral blood samples, 30 from healthy controls and 30 from asthmatic patients, were selected for a transcriptomic RNAseq study. Differential expression analysis was performed by statistical assessment of fold changes and P-values. A validation study of IL5RA expression was developed using qPCR in 100 controls and 187 asthmatic patients. The effect of benralizumab on IL5RA expression was evaluated in five patients by comparing expression levels between pretreatment and after 3 months of treatment. The IL5RA mRNA levels were normalized to GAPDH and TBP expression values for each sample. Calculations were made by the comparative ΔΔCt method. All procedures followed the MIQE guidelines.Results:IL5RA was one of the most differentially overexpressed coding transcripts in the peripheral blood of asthmatic patients (P = 8.63E-08 and fold change of 2.22). In the qPCR validation study, IL5RA expression levels were significantly higher in asthmatic patients than in controls (P < 0.001). Significant expression differences were present in different asthmatic types. In the biological drug study, patients treated with benralizumab showed a significant decrease in IL5RA expression and blood eosinophil counts. A notable improvement in ACT and lung function was also observed in these patients.Conclusions: These results indicate that IL5RA is overexpressed in patients with different types of asthma. It could help identify which asthmatic patients will respond more efficiently to benralizumab, moving toward a more personalized asthma management. Although further studies are required, IL5RA could play a role as a biomarker and pharmacogenetic factor in asthma.

Chronic Rhinosinusitis with Nasal Polyposis (CRSwNP) affects the quality of life of patients suffering from it. The search for a suitable biomarker has been conducted over the last decades. Interleukin 5 receptor subunit alpha (IL-5Rα) involves the activation, maintenance, and survival of eosinophils, which are highly tied to chronic inflammatory processes of the airways, like asthma or CRSwNP. In this study, we evaluate the utility of IL5RA as a genetic biomarker in CRSwNP. IL5RA mRNA expression level was analyzed in different groups of patients by performing qPCR assays. A significant increase in IL5RA expression was observed in CRSwNP patients, especially those with asthma and atopy. We found differences in expression levels when comparing groups with or without polyposis or asthma, as well as some atypical cases related to eosinophil levels. That opens a path to future studies to further characterize groups of patients with common features in the context of pharmacogenetics and in an era towards developing a more precise personalized treatment with IL-5Rα as a therapeutic target for CRSwNP.

One of the most critical goals in healthcare is safe and effective drug therapy, which is directly related to an individual’s response to treatment. Precision medicine can improve drug safety in many scenarios, including polypharmacy, and it requires the development of new genetic characterization methods. In this report, we use real-time PCR, microarray techniques, and mass spectrometry (MALDI-TOF), which allows us to compare them and identify the potential benefits of technological improvements, leading to better quality medical care. These comparative studies, as part of our pharmacogenetic Five-Step Precision Medicine (5SPM) approach, reveal the superiority of mass spectrometry over the other methods analyzed and highlight the importance of updating the laboratory’s pharmacogenetic methodology to identify new variants with clinical impact.

Background/Objectives: Pharmacogenetics (PGx) may improve drug safety and effectiveness, but its integration into routine care remains heterogeneous across the Spanish National Health System (NHS). This article presents BioFRAM PGx, a multicentre implementation framework that defines the methodological and operational basis for subsequent observational validation in cardiovascular and mental-health care settings. Methods: The framework was developed by healthcare centres from eight Spanish Autonomous Communities through a structured review of PharmGKB/ClinPGx clinical annotations, CPIC and DPWG guidelines, and national regulatory resources. Gene–drug pairs were prioritized according to clinical actionability, therapeutic relevance, applicability to the Spanish population, and analytical feasibility. BioFRAM PGx defines a panel of seven pharmacogenes and 35 drugs, standardized genotyping and phenotype-assignment procedures, pharmacovigilance and clinical variables, healthcare-resource measures, and centralized data management. The proposed non-interventional validation phase includes adults receiving at least one selected drug in hospital or primary-care settings, with a minimum six-month follow-up. PGx results are not returned to clinicians and do not modify treatment. Its primary objective is to assess the predictive value of PGx genotyping for adverse drug reactions (ADRs); secondary objectives include ADR incidence and implementation feasibility. Results: The main outputs are the proposed multicentre observational design, the prioritized gene–drug panel, harmonized analytical and pharmacovigilance workflows, standardized data domains, and a centralized data-management strategy. No patient-level clinical, implementation, or economic outcomes are presented. Conclusions: BioFRAM PGx provides a structured multicentre framework for harmonizing pharmacogenetic procedures across the Spanish NHS. Its clinical effectiveness, influence on prescribing, scalability, and economic outcomes remain to be assessed in subsequent studies.

Adverse effects can disrupt early treatment in first-episode psychosis and precipitate discontinuation. We report the use of the five-step precision medici