Background: Atopic dermatitis is a common inflammatory skin disorder that affects up to 15–20% of the population and is characterized by recurrent eczematous lesions with intense itching. As a heterogeneous disease, multiple factors have been suggested to explain the nature of atopic dermatitis (AD), and its high prevalence makes it necessary to periodically compile and update the new information available. In this systematic review, the focus is set at the genetic and epigenetic studies carried out in the last years. Methods: A systematic literature review was conducted in three scientific publication databases (PubMed, Cochrane Library, and Scopus). The search was restricted to publications indexed from July 2016 to December 2019, and keywords related to atopic dermatitis genetics and epigenetics were used. Results: A total of 73 original papers met the inclusion criteria established, including 9 epigenetic studies. A total of 62 genes and 5 intergenic regions were described as associated with AD. Conclusion: Filaggrin (FLG) polymorphisms are confirmed as key genetic determinants for AD development, but also epigenetic regulation and other genes with functions mainly related to the immune system and extracellular matrix, reinforcing the notion of skin homeostasis breakage in AD.

Background: Precision medicine is a promising strategy to identify biomarkers, stratify asthmatic patients according to different endotypes, and match them with the appropriate therapy. This proof-of-concept study aimed to investigate whether gene expression in peripheral blood could provide a valuable noninvasive approach for the molecular phenotyping of asthma. Methods: We performed whole-transcriptome RNA sequencing on peripheral blood of 30 non-atopic non-asthmatic controls and 30 asthmatic patients. A quantitative PCR (qPCR) validation study of PTGDR2 that encodes for CRTH2 receptor, expressed in cells involved in T2 inflammation, was developed in a cohort of 361 independent subjects: 94 non-asthmatic non-atopic controls, 187 asthmatic patients [including 82 with chronic rhinosinusitis with nasal polyposis (CRSwNP) and 24 with aspirin-exacerbated respiratory disease (AERD)], 52 with allergic rhinitis, and 28 with CRSwNP without asthma. Results: PTGDR2 was one of the most differentially overexpressed genes in asthmatic patients’ peripheral blood (p-value 2.64 × 10⁶). These results were confirmed by qPCR in the validation study, where PTGDR2 transcripts were significantly upregulated in asthmatic patients (p < 0.001). This upregulation was mainly detected in some subgroups such as allergic asthma, asthma with CRSwNP, AERD, eosinophilic asthma, and severe persistent asthma. PTGDR2 expression was detected in different blood cell types, and its correlation with eosinophil counts showed differences in some groups of asthmatic patients. Conclusions: We found that PTGDR2 expression levels could identify asthma patients, introduce a minimally invasive biomarker for adult asthma molecular phenotyping, and add additional information to blood eosinophils. Although further studies are required, analyzing PTGDR2 expression levels in peripheral blood of asthmatics might assist in selecting patients for treatment with specific antagonists.

Several biologic therapies that target inflammatory modulators are now used for treating patients with uncontrolled, severe asthma. Knowledge about how this type of treatment modifies the molecular milieu is rapidly increasing. Thus, this systematic review aimed to compile the reported effects of therapeutic antibodies on the transcriptome or proteome of asthma patients. Studies of asthmatic patients under biological treatment describing transcriptomic or proteomic changes upon treatment were included. Preclinical or single gene/protein studies were not considered. PubMed and Scopus search was performed in August and September 2021. Following PRISMA guidelines and GRADE recommendations, we selected 12 studies on gene or protein expression changes in patients treated with the antibodies currently approved by EMA and the FDA. All studies were at low risk of bias as per the RoB2 tool. Different gene clusters have been identified to change upon omalizumab treatment, found a reduction in eosinophil-associated gene signatures after benralizumab treatment, and protein profiles were different in patients treated with mepolizumab and in those treated with benralizumab. The main potential biomarkers proposed by the selected studies are shown. These results may contribute to discovering biomarkers of response and selecting the best therapy for each patient.